Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.6886586
The availability of free IGF 1 for interaction with IGF IR is modulated by IGF binding proteins ( IGFBP 1 6 ) . 0.6886586^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.5303353
Primary human T , pre B and cALL cells also expressed IGF IR with Kd for IGF 1 and IGF IR number per cell in the same range as the investigated cell lines . 0.5303353^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.66753175
A model is presented in which one or two molecules of ligand can be bound to an alpha 2 beta 2 IGF 1 receptor heterotetramer , new ligand becomes associated with receptor by exchanging for a previously bound molecule of IGF 1 , and fluctuating changes in free ligand concentration might lead to enhanced IGF 1 function . . 0.66753175^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.66777226
From E13 . 5 onward , IGF1R interacts with both IGF 1 and IGF 2 , while IGF 2 recognizes an additional unknown receptor ( XR ) . 0.66777226^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.53438352
In contrast , des ( 1 3 ) IGF 1 manifested a remarkably higher potency as compared with IGF 1 in inducing short and middle term cellular responses in IGF IR transfected Ishikawa endometrial cancer cells possessing a high number of both the receptor and the cell membrane bound IGFBP 3 . 0.53438352^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.54398664
Different domains of the IGF 1 receptor were expressed as ( His ) 6 tagged fusion peptides , phosphorylated with activated wheat germ agglutinin purified IGF 1 receptors and tested for association with GST Crk 2 fusion proteins . 0.54398664^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.59240898
Here we show that an IGF 1 receptor antagonist suppresses retinal neovascularization in vivo , and infer that interactions between IGF 1 and the IGF 1 receptor are necessary for induction of maximal neovascularization by vascular endothelial growth factor ( VEGF ) . 0.59240898^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.63102648
IGF 1 binds to the IGF 1 receptor and thereby induces the autophosphorylation of this receptor at its tyrosine residues . 0.63102648^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.79074071
The availability of unbound IGF 1 for interaction with IGF1R is modulated by IGF binding proteins ( IGFBP 1 6 ) . 0.79074071^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNAs for mechano growth factor , IGF binding protein 5 , and the IGF 1 receptor were unchanged by RE . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGFBP 1 , a nonglycosylated peptide , competes with the IGF 1 receptor for ligand binding and also regulates IGF action . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Receptor binding analyses revealed that both cell types possess the type 1 IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Control pachymeninges ( dura mater ) expressed low levels of IGF 1 mRNA and IGF 1 receptor mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor studies are needed to test this speculation about IGF 1 resistance . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dissociation rate constant of the IGF 1 receptor was 3 . 10 + / 0 . 06 nmol / l ( S . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding affinity and capacity of IGF 1 receptor was constant throughout the oestrous cycle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor 1 receptor ( IGF 1 R ) gene is expressed in most body tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The binding characteristics were found to be compatible with binding to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor as the restriction point of the cell cycle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In these cells , therefore , insulin was active via both its own receptor and the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both types of cells expressed the IGF 1 receptor and showed high contact inhibition . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Further studies with isolated bovine chondrocytes revealed that H2O2 did not damage the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and IGF 1 receptor in mouse colon cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and insulin receptor mRNA could be detected on Northern blot without any degradation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor binding to HEC 1B and KLE cells was inhibited in the presence of purified IGFBP 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Signal transduction by IGF 1 receptor kinase ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The pp 150 and pp 160 might be endogenous substrates of IGF 1 receptor kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A mouse monoclonal antibody to the IGF 1 receptor inhibited the stimulation of insulin in JEG 3 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of alpha IR 3 , an IGF 1 receptor antibody , eliminated the IGF 1 chemotactic response . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody to IGF 1 receptor was able to inhibit PC cell growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The characteristics of the endometrial IGF 1 receptor are similar to those reported for other tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Via interaction with its own receptor and the IGF 1 receptor , insulin induced a mitogenic response in these cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly IGF 1 binding to IGF 1 receptor ( KD 0 . 38 nM ) could be inhibited by insulin ( KD 53 . 7 nM ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor alpha subunits of SK N SH have an apparent Mr of 126K , whereas that for SK N MC is 132K . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Denervation ( 24 h ) produced severe IGF 1 resistance without affecting IGF 1 receptor number or affinity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A specific high affinity IGF 1 receptor was also identified , with a Kd of approximately 10 ( 9 ) M / liter . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An IGF 1 receptor monoclonal antibody ( alpha IR 3 ) inhibited 125I IGF 1 but not 125I insulin binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The lower potency of insulin may indicate that the effect of insulin on hPL production is via IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This effect of insulin may be mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Therefore , both human insulins were evaluated in terms of binding to the IGF 1 receptor in chick embryo fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mechanism of insulin and IGF 1 receptor activation and signal transduction specificity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor : a new antiproliferative marker ? ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA in the hypertrophying bladder remained unchanged . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The number of IGF 1 receptors and IGF 1 receptor mRNA levels can be up regulated by hCG . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor mRNA did not change significantly . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both of these two types of cells expressed mRNA for IGF 1 receptor and the expression was not affected by androgen . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RFLPs at the baboon insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor ( IGF1R ) loci . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor binding was , in addition , highly specific . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The applied immunohistochemical approach detected IGF 1 receptor synthesis in endothelial cells of atherosclerotic vessels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These autoantibodies interfere with receptors , e . g . the TSH receptor or the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor binding parameters were measured from saturation experiments with 125I IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Neither STZ D nor insulin treatment affected IGF 1 or IGF 1 receptor mRNA concentrations in the kidney . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This result suggest the presence of a limiting step , distal to the IGF 1 receptor , in the transduction pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blocking of the IGF 1 receptor inhibited ICC formation but did not affect their insulin content . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The biological signal of both factors is transmitted through the IGF 1 receptor ( IGF 1 R ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
TSH uses cAMP as a second messenger , whereas the IGF 1 receptor possesses protein tyrosine kinase activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The high affinity IGF binding by the IGF 1 receptor is determined by its cysteine rich domain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cell cycle control by the IGF 1 receptor and its ligands . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The regulation of IGF 1 receptor gene expression by positive and negative zinc finger transcription factors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Differences in insulin and IGF 1 receptor number alone could not explain these results . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This interaction does not appear to occur with the similar , although distinct , IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and the IGF 1 receptor in development of nonmammalian vertebrates . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This suggests that the overexpression of IGF 1 receptor may reflect the malignant potential of bladder cancer cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of the IGF 1 receptor in the stimulation of cells by short pulses of growth factors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It did not affect either autophosphorylation of the IGF 1 receptor or calcium entry induced by IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Serum deprivation for 48 hours caused a 40 % decrease in IGF 1 receptor number . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The ratio of potency of IGF I / IGF 2 was 1 : 5 for the IGF 1 receptor and 100 : 1 for the IGF 2 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA was expressed in low abundance in all cell types of the placenta . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor protects tumor cells from apoptosis induced by high concentrations of serum . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor gene promoter is a molecular target for the Ewing ' s sarcoma Wilms ' tumor 1 fusion protein . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recent data suggest that IGFs may also be involved in tamoxifen resistance , through upregulation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor gene from HSIGFIRR clone contains the region with latent period 57 bases long . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Sos complexes from the IGF 1 receptor , as it is from the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This effect may be mediated by either the insulin or the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Oestradiol , which potentiates the effect of ovariectomy on milk synthesis , increases IGF 1 receptor concentrations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Finally , mRNA levels for the IGF 1 receptor were similar in all experimental groups . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Variations at the IGF 1 receptor level were tested by binding studies on cell monolayers . 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
No change was detected in renal IGF 1 receptor mRNA levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Role of the IGF 1 receptor in mutagenesis and tumor promotion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Its observed actions are probably based on its metabolic effects and are mediated by the insulin or the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We identified insulin receptor substrate 1 ( IRS 1 ) as a common substrate for insulin and IGF 1 receptor tyrosine kinases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , the extracted peptide bound competitively to a membrane IGF 1 receptor preparation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor in cell growth , transformation and apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of the IGF 1 receptor in apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Localization of IGF 1 and IGF 1 receptor mRNA in Sparus aurata larvae . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor numbers increase in the presence of FSH , while estradiol has a synergic effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transcripts of messenger RNAs of both IGF 1 and IGF 2 and both IGF IR and IGF IIR also were detectable by Northern analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The actions of IGF 1 and IGF 2 are mediated via the IGF 1 receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin receptor ( IR ) shares structural and functional homology with the IGF 1 receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor and cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The activity of CGF was inhibited by antibodies to insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There was also a small increase ( 70 % ) in IGF 1 receptor ( IGF 1R ) at day 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cloning of the IGF 1 receptor cDNA of turbot ( Scophthalmus maximus ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor protection from apoptosis in cells lacking the IRS proteins . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Treatments greater than 10 UI of hCG resulted in a significant suppression of mammary IGFBP 3 and IGF 1 receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Total IGF 1 receptor mRNA was unchanged by the injury . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
TNF alpha also decreases IGF 1 receptor levels in MCF 7 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed that IGF 1 receptor mRNA was expressed in all of the 3 above generation tendon cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the tissue abundance of the IGF 1 receptor in the stomach and ileum was greater in Dex pigs than controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor 1 receptor ( IGF IR ) mediates the biological actions of IGF 1 and IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dissociation between resistance to apoptosis and the transformed phenotype in IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Anti apoptotic signaling of the IGF 1 receptor in fibroblasts following loss of matrix adhesion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Their effects are mediated via the IGF 1 receptor ( IGF IR ) that is essential for growth in these cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , IGF 1 receptor and oestrogen receptor beta mRNA contents were determined by semiquantitative RT PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Characterization of an antibody that can detect an activated IGF 1 receptor in human cancers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
ANG 2 decreased IGF 1 , IGFBP 2 , and IGFBP 4 transcripts but increased the IGF 1 receptor transcript . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The four most active compounds were shown to inhibit IGF 1 stimulated IGF 1 receptor autophosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , there was no effect of relaxin on GC IGF binding proteins or IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor in cancer research . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 induced the release of the G ( beta ) subunits from the IGF IR but had no effect on the association of G ( alphai ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transgene expression led to activation of the IGF 1 receptor and spontaneous tumorigenesis in prostate epithelium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There were no differences between +BP3 and Mock cells in IGF 1 receptor number or affinity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , IGF 2 and the IGF IR were expressed in terminal end buds ( TEBs ) in virgin glands during ductal growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Function of the IGF 1 receptor in breast cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor signaling in a prostatic cancer cell line with a PTEN mutation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Distribution of the two types of IGF 1R and IGF 1 in gonads was studied by immunohistochemistry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and beta actin mRNAs were induced by 6 and 2 fold , respectively , as a function of confluence . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both ligands ( IGF 1 and IGF 2 ) signal via the same IGF receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Erythrocyte IGF 1 receptor binding is known to be affected by circulating levels of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reduced MAP kinase activation is not associated with alterations in IGF 1 receptor autophosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA levels were significantly reduced in obese rat hearts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In 7 of these , the IGF 1 receptor ( IGF IR ) was expressed and autophosphorylated in response to ligand . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
After IGF 1 induction , EHD 1 and IGF 1R co localize intracellularly . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IgG NOV was not able to stimulate the autophosphorylation of the human IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and the IGF 1 receptor are necessary for normal embryonic growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The high resolution crystal structure of an N terminal fragment of the IGF 1 receptor , has been reported . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cloning of porcine IGF 1 receptor cDNA and detection of sequence polymorphisms using RT PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effect of IGF 1 receptor gene antisense oligodeoxynucleotide on T 24 urinary bladder cancer cells ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we showed IGF 1 and IGF 1 receptor mRNA expression by human and murine TEC and thymocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Increased insulin sensitivity in IGF 1 receptor deficient brown adipocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In many tissues , the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) is known to functionally oppose apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Treatment of SH EP / pSFFV cells with IGF 1 or transfection of IGF 1 receptor prevents these changes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor expression protects against microenvironmental stress found in the solid tumor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
One central player in the prevention of cell death is the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF IR ligands , IGF 1 and IGF 2 , are mitogens and survival factors for many cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Further examination showed a higher level of IGF 1 receptor mRNA in the tumor than in the normal liver parenchyma . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor is mediated by serine autophosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mechanism of IGF 1 receptor activation and signal transduction specificity ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor antibody alphaIR 3 or the PI 3 kinase inhibitor wortmannin prevented the functional effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF IR ) are involved in growth of neurons . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We previously identified the IGF 1 receptor as a positive regulator of MMP 2 synthesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF 1 ) and its receptor ( IGF IR ) are highly expressed in this tumor type . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF1R ) mRNA levels were decreased in the CR Std group but were increased in the CR Ket diet group . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The potential role of IGF 1 receptor mRNA in rats with diabetic retinopathy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These actions are mediated by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGFs exert these biological actions through the activation of the IGF 1 receptor and its downstream signaling network . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dominant negative IGF 1 receptor ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of IGF 1 receptor blockage on cell proliferation and anchorage independent cell growth was also examined . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor in cancer biology . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ameloblast apoptosis and IGF 1 receptor expression in the continuously erupting rat incisor model . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There are three ligands for IGF 1R : IGF 1 , IGF 2 and insulin at supraphysiological concentrations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Regulation of IGF 1 receptor signaling in tumor cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of the IGF 1 receptor in the regulation of matrix metalloproteinases , tumor invasion and metastasis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Prenatal overgrowth and mosaic trisomy 15q25 qter including the IGF 1 receptor gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study we demonstrated that 14 3 3sigma is a positive mediator of IGF 1 receptor induced cell proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Altered IGF 1 receptor expression in chorioamniotic cells in premature rupture of fetal membranes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and the IGF 1R specific analog Des ( 1 3 ) also induce cytokine production in RA fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 2 induced apoptosis could not be inhibited by a blocking antibody to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor , cell cell adhesion , tumour development and progression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Targeting the IGF 1 receptor : from rags to riches . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The levels of IGF 1 receptor ( IGF IR ) mRNA increased from 10 days to 4 weeks after the EBr injection . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Nitric oxide decreases IGF 1 receptor function in vitro ; glutathione depletion enhances this effect in vivo . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
AIB 1 reduction decreased the expression of the IGF 1 receptor and IRS 1 in MCF 7 but not in MDA MB 231 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found increased IGF 1 receptor ( IGFR ) expression and activation , including activation of MAPK . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and IGF 1 receptor trafficking and signalling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , DETC deficient mice had reduced IGF 1 receptor activation at wound sites . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PGF2alpha increased the steady state levels of IGF 1 receptor mRNA while PGE 2 increased IGF 1 expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Oxidative stress induces IGF 1 receptor signaling disturbances in cultured human dermal fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
SOCS 3 gene expression is induced , at least in part , by activation of the IGF 1 receptor during myoblast differentiation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The very low level of IGF IR at the plasma membrane of Huh 7 cells may account for their unresponsiveness to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Likewise , deletion of the IGF 1 receptor in muscle in mice induces severe insulin resistance . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PTEN overexpression resulted in a significant decrease in the expression of IGF 1 , 2 , and IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF Ir / dn blocked Akt 1 activation induced by IGF 1 , IGF 2 , and des ( 1 3 ) IGF 1 , but not by insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The importance of IGF signal in hepatic metastasis has been clarified mainly by IGF 1 receptor targeting strategies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Gene expression profiles in cells transformed by overexpression of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this signalling the IGF 1 receptor ( IGF 1R ) is unquestionable , the predominating single factor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor and its contributions to metastatic tumor growth novel approaches to the inhibition of IGF 1R function . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Studies involving the GH IGF axis : Lessons from IGF 1 and IGF 1 receptor gene targeting mouse models . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transformation by the simian virus 40 T antigen is regulated by IGF 1 receptor and IRS 1 signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of IGFBP 3 was independent of the blockade of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor levels were 1 . 15 + / 0 . 83 in the normal and 0 . 31 + / 0 . 22 in the liver disease group ( p < 0 . 05 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
JAK 1 and Tyk 2 activation by the homologous polycythemia vera JAK 2 V617F mutation : cross talk with IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The actions of IGF 1 and IGF 2 are thought to be largely due to their activation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGFBP 3 , IGF 1 , IGF 1 receptor and GH receptor mRNA levels were quantified using real time RT PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor inhibition prevents rapamycin induced Akt activation and sensitizes tumor cells to inhibition of mTOR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockade of IGF 1 receptor tyrosine kinase has antineoplastic effects in hepatocellular carcinoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By contrast , both IGF 1 receptor and insulin receptor mRNA levels increase in day 7 AH 130 hosts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Overexpression of IGF 1 receptor ( IGF IR ) increased basal glucose uptake in neonatal hepatocytes lacking or not IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSION : IGF 1 deficiency and / or IGF IR resistance induced apoptosis in cardiomyoblast cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Folic acid and its metabolites modulate IGF 1 receptor gene expression in colon cancer cells in a p 53 dependent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The phenomenon was related to the inhibition of beta ( 1 ) integrin and IGF 1 receptor mediated signaling caused by AB 4 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effect of blocking IGF 1 receptor on growth of human hepatocellular carcinoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , the progenitors in both the SVZ and DG showed IGF 1 receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The significant changes associated with the inability of the older muscles to respond to mechanical overload included the considerably lower expression of the local splice variant mechano growth factor , and the failure to up regulate IGF 1 receptor and MyoD mRNA . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blocking the IGF 1 receptor with a specific antibody indicated that the function of MGF E domain is mediated via a different receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
While two peptides showed an additive effect , the neuroprotective action of the C terminal MGF was independent from the IGF 1 receptor , indicating a new mode of action for this molecule . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In situ hybridization was used to map patterns of gene expression for components of the insulin like growth factor ( IGF ) system , including IGF 1 and 2 , IGF binding proteins 1 5 ( IGFBP 1 5 ) , the IGF 1 receptor , and GH in the rat pituitary . ^^^ IGF 1 receptor mRNA was abundant and homogeneously distributed throughout the AL and IL , compatible with expression by endocrine cells . ^^^ IGF 1 receptor mRNA , which might have been expected to localize to somatotrophs , appears to be equally abundant in all of the endocrine cells of both AL and IL ; the other constituents of the IGF system are localized in connective tissue and support elements that demonstrate no special anatomical relationship to somatotrophs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
No evidence could be provided that IGF 1 plays any role in the LH induction of the CSCC enzyme ; neither the addition of exogenous IGF 1 or analogs that do not bind to IGF 1 binding proteins ( IGFBPs ) nor the inactivation of endogenous IGF 1 action ( through binding to IGFBP and antibodies to IGF 1 or via masking of IGF 1 receptor by antibodies ) could influence the LH induced CSCC enzyme activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have found that over one half of the total cell surface 125I insulin like growth factor 1 ( IGF 1 ) binding to BHK cells represents binding to IGF binding proteins ( IGFBPs ) rather than to the IGF 1 receptor . ^^^ At high concentrations of IGF 1 , IGFBP secretion increases and cell surface IGF 1 receptor , as well as IGFBP , decreases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Additionally , IGF 1 binding is increased in diabetic rat kidney , due to increased binding to the IGF 1 receptor and induction of proximal tubular binding protein expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
DNA and RNA analysis of these cells and of five clones of IGF 1 responsive cells demonstrated that the IGF 1 receptor gene was not rearranged nor was it abnormally expressed in IGF 1 responsive cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The double life of the IGF 1 receptor . ^^^ The IGF 1 receptor is expressed in many cell types , and its activation by its ligands is a required step for the proliferation of many cells in vivo and in vitro . ^^^ In most cells in culture , requiring more than one growth factor for growth , the IGF 1 receptor can be found in one of two different modes : in the first mode , although it is autophosphorylated by its ligands and induces the expression of specific genes , it does not transmit a mitogenic signal . ^^^ In the alternative mode , i . e . , after priming with an unrelated growth factor , the IGF 1 receptor responds to its ligands with a mitogenic stimulus . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor that is a tyrosine kinase and closely related with the insulin receptor and the IGF II / mannose 6 phosphate ( IGF II / Man 6 P ) receptor that is identical with the cation independent mannose 6 phosphate receptor . ^^^ The mitogenic and metabolic actions of IGF 2 are propagated by the IGF 1 receptor . ^^^ In this scenario IGF 2 promotes the growth of the embryo through the IGF 1 receptor , whereas the IGF II / Man 6 P receptor balance the activity by controlling the extracellular level of IGF II . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The actions of the IGFs are mediated through their activation of specific cell surface receptors , primarily the IGF 1 receptor , although some effects may be mediated through the IGF 2 receptor and the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Steady state levels of IGF 1 mRNA as well as IGF 1 receptor and IGF II / mannose 6 phosphate receptor mRNAs were increased 3 to 4 fold in immature remnant kidneys , but not in adult kidneys . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The tyrosine kinase activity of the IGF 1 receptor beta subunit was stimulated by IGF 1 , IGF 2 , and insulin , in order of potency , suggesting that these peptides exert a regulatory function in the choroid plexus epithelium . ^^^ In conclusion , we propose that the IGF 1 receptor tyrosine kinase on the surface of the epithelial cells in the pig choroid plexus mediates effects of IGF 1 and IGF 2 , whereas IGF 2 receptors are down regulated due to the synthesis and secretion of IGF 2 in these cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study describes the expression of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) genes in the mouse uterus during the peri implantation period ( Days 1 6 of pregnancy ) , as well as effects of estradiol ( E ) and progesterone ( P ) on cell specific IGF 1 gene expression in the uterus of the ovariectomized adult mouse . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Stimulation by insulin like growth factor 1 ( IGF 1 ) of LISN C 4 cells , a mouse fibroblast cell line that overexpresses human IGF 1 receptors , led to an increase in the amount of a phosphatidylinositol kinase that could be immunoprecipitated by anti IGF 1 receptor or anti phosphotyrosine antibodies . ^^^ The identity of the lipid produced in phosphatidylinositol kinase assays of anti IGF 1 receptor or anti phosphotyrosine immunoprecipitates indicated that IGF 1 selectively increased the amount of immunoprecipitated phosphatidylinositol 3 kinase activity . ^^^ The amount of immunoprecipitated phosphatidylinositol 3 kinase activity that was increased by IGF 1 followed a time course that paralleled the stimulation of IGF 1 receptor beta subunit autophosphorylation . ^^^ The amount of phosphatidylinositol 3 kinase activity detected in anti IGF 1 receptor immunoprecipitates represented only 2 % of that which was immunoprecipitated by anti phosphotyrosine antibody . ^^^ Taken together , these results suggest that the stimulation of the IGF 1 receptor tyrosine kinase leads to an increase in the amount of phosphatidyl inositol 3 kinase activity immunoprecipitated by antiphosphotyrosine and anti IGF 1 receptor antibodies and to a limited association with the IGF 1 receptor itself , even though these cells express very high levels of IGF 1 receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Preincubation of intact cells with TSH increased by 2 fold insulin and IGF 1 receptor autophosphorylation and phosphorylation of the p 175 endogenous substrate for the receptors . ^^^ At variance with TSH , cell incubation with either 8 bromo cAMP or the protein kinase C activator 12 O tetradecanoylphorbol 13 acetate inhibited insulin and IGF 1 receptor kinases . ^^^ In intact cells , TSH stimulation of insulin and IGF 1 receptor kinases was accompanied by enhanced turnover of phosphate on autophosphorylated receptors , increased receptor tyrosine phosphorylation , and decreased receptor serine / threonine phosphorylation in response to insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast when alpha IR 3 , a monoclonal antibody that recognizes typical IGF 1 receptor , was employed over 60 % of 125I insulin binding was inhibited . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similar assays were used to measure the levels of IGF 1 receptor mRNA and GH receptor mRNA , while the IGF 1 concentration in wound fluid and serum was determined by radioimmunoassay ( RIA ) after acid ethanol extraction . ^^^ There was no significant effect of GH on IGF 1 receptor mRNA and GH receptor mRNA levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The pattern of IGF 1 receptor expression in normal skin is distinct from that of the epidermal growth factor ( EGF ) receptor , suggesting that these receptors might be differentially regulated . ^^^ The purpose of this study was to obtain a better understanding of IGF 1 receptor function in the skin by examining IGF 1 receptor expression in psoriatic epidermis and in cultured human keratinocytes . ^^^ Our findings indicate that IGF 1 receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF 1 receptor specific monoclonal antibody . ^^^ Unlike EGF receptor expression , which is also increased in psoriatic epidermis , the pattern of IGF 1 receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis . ^^^ Biochemical agents that diminish EGF receptor ligand binding ( phorbol ester or calcium ionophore treatment ) produce opposite effects on the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The existence of specific and functional IGF 1 receptors on circulating bovine mononuclear cells would provide an easily accessible source for studying IGF 1 receptor changes in the bovine , both in physiologic and pathologic states . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effect of a growth hormone releasing factor antagonist on compensatory renal growth , insulin like growth factor 1 ( IGF 1 ) , and IGF 1 receptor gene expression after unilateral nephrectomy in immature rats . ^^^ In addition , insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor mRNA levels were elevated 3 fold in the remnant kidneys of GRF AN treated rats , despite the suppression of pulsatile GH release . ^^^ These findings suggest that the initial phase of CRG is GH independent in the immature rat and , further , that CRG is associated with an increase in IGF 1 and IGF 1 receptor gene expression that is independent of episodic GH secretion . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effect of testosterone on insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression in the hypophysectomized rat . ^^^ This study was designed to determine whether T has a direct effect on IGF 1 serum levels , liver IGF 1 gene expression , and epiphyseal growth plate IGF 1 and IGF 1 receptor gene expression . ^^^ IGF 1 receptor mRNA abundance was not significantly different in the T group compared to that in the control group . ^^^ GH decreased IGF 1 receptor mRNA by 2 . 3 fold , but T treatment before GH injection did not change this effect . ^^^ T alone also does not have a stimulatory effect on IGF 1 or IGF 1 receptor gene expression in the epiphyseal growth plate region . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An antibody that blocks the IGF 1 receptor does not inhibit either peptide activity , while an antibody specific for the IGF 2 receptor suppresses the IGF 2 induced motility . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody to the T cell receptor increases IGF 1 receptor content in normal T lymphocytes : comparison with phytohemagglutinin . ^^^ It has been previously reported that mitogenic activation of T lymphocytes by phytohemagglutinin ( PHA ) is associated with increased IGF 1 receptor content . ^^^ However , the mechanisms which regulate IGF 1 receptor expression during T lymphocyte activation are unknown . ^^^ To explore further the regulation of IGF 1 receptor expression in T cells , we investigated IGF 1 receptor content and mRNA abundance in T lymphocytes after stimulation either by PHA or OKT 3 , the latter being a monoclonal antibody directed against the CD 3 antigen of the T cell receptor . ^^^ IGF 1 binding in T cells demonstrated increased IGF 1 receptor content after stimulation by both PHA and OKT 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To approach the question of why insulin like growth factor 1 ( IGF 1 ) and insulin have different physiological actions , we developed antibodies directed against cytoplasmic regions of the IGF 1 receptor exhibiting a low degree of homology with the corresponding sequences of the insulin receptor . ^^^ We found that an antipeptide antibody directed against the beta subunit carboxyl terminal sequence ( 1232 1246 ) of the IGF 1 receptor significantly reduced the in vitro receptor autophosphorylation . ^^^ The ability of the synthetic peptide corresponding to the IGF 1 receptor sequence 1232 1246 to abolish this inhibitory effect reflects the specific nature of the antibody interaction with the targeted domain in the receptor . ^^^ Antipeptide antibody to IGF 1 receptor sequence 1232 1246 also decreased receptor phosphorylation activity toward the exogenous substrate poly ( Glu / Tyr ) . ^^^ Taken together our data suggest that the beta subunit carboxyl terminal domain of the IGF 1 receptor plays a key role in regulating its kinase activity and that the particular sequence recognized by our antipeptide antibody could be involved in negative regulation of receptor functioning . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have isolated and characterized human genomic DNA clones containing the entire coding sequence of the IGF 1 receptor . ^^^ Results of restriction analysis and sequencing of multiple overlapping clones were consistent with the existence of a single IGF 1 receptor gene . ^^^ Knowledge of the structure of the IGF 1 receptor gene should facilitate further studies on the structural determinants of receptor function , the relationships between insulin and IGF 1 receptors , and the molecular basis for multiple IGF 1 receptor species . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Preimplantation parthenogenetic mouse embryos expressed mRNA for the IGF 2 receptor but not for either IGF 2 ligand or the IGF 1 receptor , indicating that the latter genes are not expressed when inherited maternally . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , IGF 1 receptor , and epidermal growth factor receptor mRNAs were seen in both the tumor cells of the gastric cancer specimens and in nonmalignant mucosa . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) stimulates the production of 3 inositides and markedly increases the phosphatidylinositol 3 kinase activity that is immunoprecipitated by anti phosphotyrosine antibodies , a portion of which is also associated with the IGF 1 receptor . ^^^ In this study , recombinant p 85 , the regulatory subunit of phosphatidylinositol 3 kinase , and fusion proteins containing various subdomains were used to investigate the association of p 85 with the IGF 1 receptor and to demonstrate that p 85 is a direct in vitro substrate of the IGF 1 receptor kinase . ^^^ Solubilized IGF 1 receptor was immobilized on antireceptor antibody agarose beads . ^^^ A fusion protein containing the SH 2 domains of Ras GTPase activating protein also inhibited the association of phosphatidylinositol 3 kinase activity with immobilized IGF 1 receptor , although less effectively than p 85 , whereas a similar construct containing the SH 2 domain of pp60src was without effect . ^^^ When immobilized phosphorylated IGF 1 receptor was incubated with intact p 85 or the SH 2 containing fusion proteins , it became associated with and phosphorylated these proteins . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Subtypes of insulin growth factor 1 ( IGF 1 ) receptors , including hybrid receptors containing insulin receptor alpha beta dimers associated with IGF 1 receptor alpha beta dimers , have been described in a number of systems . ^^^ IGF 1 receptors containing 102 kDa beta subunits are immunoprecipitated by the IGF 1 receptor specific antibody alpha IR 3 . ^^^ The inability of antibody alpha IR 3 to recognize these complexes suggests that their IGF 1 receptor alpha subunits must differ from typical IGF 1 receptor alpha subunits either in primary sequence or conformation . ^^^ Therefore , KB cells may contain more than one type of IGF 1 receptor alpha subunit . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Three IgG mAbs were specific for the human IGF 1 receptor and displayed negligible crossreactivity with the human insulin receptor . ^^^ With the purified IGF 1 receptors , both inhibitory and stimulatory mAbs were shown to activate autophosphorylation of the IGF 1 receptor beta subunit and to induce microaggregation of the receptors . ^^^ These results suggest that conformational changes resulting from receptor dimerization in the presence of either type of mAb may affect the signal transducing function of the IGF 1 receptor differently . ^^^ These additional mAbs and alpha IR 3 immunoprecipitated nearly 90 % of IGF 1 binding activity from Triton 10 100 solubilized human placental membranes , indicating that IGF 1 receptor reactive with these mAbs is the major form of the IGF 1 receptor in human placenta . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This suggests that , in isolated humans , endometrial cell modulation of IGF 1 receptor function by estrogen and P does not occur . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have previously shown , using truncated soluble recombinant receptors , that substituting the 62 N terminal amino acids of the alpha subunit from the insulin like growth factor 1 receptor ( IGFIR ) with the corresponding 68 amino acids from the insulin receptor ( IR ) results in a chimeric receptor with an approximately 200 fold increase in affinity for insulin and only a 5 fold decrease in insulin like growth factor 1 ( IGFI ) affinity ( Kjeldsen , T . , Andersen , A . ^^^ Furthermore , this domain can be subdivided into two regions ( amino acids 1 27 and 28 68 of the IR alpha subunit ) that , when replacing the corresponding IGFIR sequences , increases the insulin affinity of truncated soluble receptor chimeras 8 and 20 fold , respectively , with only minor effects on the IGFI affinity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin / IGF 1 receptor hybrids : a mechanism for increasing receptor diversity . ^^^ Cells expressing both receptors also express hybrid receptors that contain one insulin receptor alpha and beta subunit , and one IGF 1 receptor alpha and beta subunit . ^^^ Although not yet examined in detail , both the hormone binding and the signaling properties of the hybrid receptor appear to be different from that of either insulin or IGF 1 receptor . ^^^ Regulatory mechanisms that involve either insulin or IGF 1 receptor , at the level of expression or subsequently , could alter the expression or function of the hybrid receptor or the other receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptors on the cells were characterized by competitive binding assays , chemical crosslinking and northern blot hybridization of IGF 1 receptor mRNA . ^^^ The IGF 1 binding was inhibited by the IGF 1 receptor antibody ( alpha IR 3 ) . ^^^ Northern blot hybridization indicated that IGF 1 receptor mRNA was being produced by all SCLC and NSCLC cell lines . ^^^ The data indicate that the IGF 1 receptor thus appears to be the common pathway for the mitogenic activity of IGF 1 and IGF 2 with regard to human lung cancer cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The biological activity of insulin like growth factor 1 ( IGF 1 ) is mediated by a transmembrane glycoprotein ( type 1 IGF receptor or IGF 1 receptor ) that shows considerable sequence homology with the insulin receptor . ^^^ In order to detect the expression of this gene in chicken liver tissue , a plasmid was constructed containing a fragment of chicken IGF 1 receptor cDNA . ^^^ The cDNA fragment corresponded to nucleotides 326 599 of the human IGF 1 receptor cDNA and showed 86 . 1 and 69 . 3 % homology at the nucleotide level and 96 . 7 and 80 . 2 % homology at the amino acid level with the human IGF 1 receptor and insulin receptor respectively . ^^^ The construct was used to generate an antisense RNA probe for the detection of IGF 1 receptor mRNA transcripts in 1 and 4 week old chick liver tissue . ^^^ IGF 1 receptor gene expression was initially detected by the reverse transcriptase polymerase chain reaction using synthetic chicken IGF 1 receptor oligonucleotides . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although the regulation of the insulin receptor tyrosine kinase has been extensively investigated , the mechanisms involved in phosphorylation / dephosphorylation of the IGF 1 receptor have received only little attention . ^^^ To obtain a better understanding of the mode of IGF 1 action , we have investigated the effects of protein phosphotyrosine phosphatases ( PTPases ) on the phosphorylation status of the IGF 1 receptor . ^^^ The dephosphorylation of the human IGF 1 receptor by membrane associated tyrosine phosphatases was studied by an immuno enzymic assay based on the recognition of phosphotyrosine residues by anti phosphotyrosine antibodies . ^^^ Tyrosine kinase activity and autophosphorylation of the IGF 1 receptor were decreased in a dose dependent manner by PTPases , indicating that partial dephosphorylation of the receptor was associated with a decrease in its intrinsic activity . ^^^ The sensitivity of the activated human IGF 1 receptor to dephosphorylation on tyrosine leads to the speculation that IGF 1 receptor activity might be regulated by mechanisms such as those described for the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Solution hybridization / RNase protection assays were used to study the developmental expression of the insulin like growth factor 1 ( IGF 1 ) , IGF 2 , IGF 1 receptor , and IGF II / mannose 6 phosphate receptor genes in the rat ovary between postnatal days 1 80 . ^^^ IGF 1 receptor mRNA levels increased 10 fold to a maximum in the 20 to 25 day postnatal period . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Roles of insulinlike growth factor 1 ( IGF 1 ) and the IGF 1 receptor in epidermal growth factor stimulated growth of 3T3 cells . ^^^ When BALB / c3T3 cells are transfected with plasmids constitutively expressing both EGF and the human IGF 1 receptor mRNAs , the cells are capable of growing in serum free medium without the addition of any exogenous growth factor . ^^^ BALB / c3T3 cells transfected with only the IGF 1 receptor expression plasmid ( p 6 cells ) do not grow in serum free medium but do grow if IGF 1 ( or insulin in supraphysiological concentrations ) is added . p 6 cells also grow in response to EGF , confirming that the combination of EGF and an overexpressed IGF 1 receptor is sufficient for the growth of 3T3 cells . ^^^ We have found that in EGF stimulated p 6 cells there is an increase in the expression of IGF 1 mRNA , that IGF 1 is secreted into the medium , and that the growth of p 5 cells and EGF stimulated p 6 cells is inhibited by exposure to antisense oligodeoxynucleotides to IGF 1 receptor RNA . ^^^ Finally , while cells constitutively expressing both EGF and EGF receptor RNAs grow , albeit modestly , in serum free medium , their growth is also inhibited by an antisense oligodeoxynucleotide to IGF 1 receptor RNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of growth hormone receptor , insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor mRNA and proteins in human skin . ^^^ In contrast , IGF 1 receptor mRNA were abundant in cultured keratinocytes and skin biopsies , as determined by Northern analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 exhibited a high affinity for the IGF 1 receptor ( apparent Kd approximately 3 nM ) . ^^^ The inhibitory effect of IGFs and insulin on EPO formation appears to be mediated via the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BALB / c3T3 cells that constitutively express IGF 1 and elevated levels of IGF 1 receptor ( IGF 1R ) are capable of growth in serum free medium without the addition of any exogenous growth factors . ^^^ BALB / c3T3 cells overexpressing only the IGF 1R plasmid required IGF 1 or insulin for serum free growth . ^^^ Antisense oligodeoxynucleotides complementary to IGF 1R mRNA inhibited IGF 1 mediated cell growth . ^^^ These findings indicate that constitutive expression of IGF 1 and IGF 1R allows 3T3 cells to grow in serum free medium without addition of those exogenous growth factors that are required by the parent cell line . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , a monoclonal antibody antagonist to the IGF 1 receptor ( alpha IR 3 ) did not suppress the proliferative response induced by Y 23 R NH 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity cross linking of [ 125I ] IGF 1 to microsomal membranes , under reducing conditions , revealed a binding moiety with an apparent molecular mass of 130 kDa in permissive cells and 140 kDa in inducible cells , which corresponded to the alpha subunit of the IGF 1 receptor . ^^^ It emerges from these experiments that C 2 cells express a putative alpha 2 beta 2 IGF 2 receptor structurally related to the insulin / IGF 1 receptor family . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Basal DNA synthesis of the early differentiated T cell lines HSB 2 and HUT 78 , as well as the B cell line REH , could be inhibited in a dose dependent manner by both monoclonal antibodies against IGF 1 ( ASC 41 ) and antibodies against the IGF 1 receptor ( alpha IR 3 ) , suggesting that IGF 1 acts as an auto or paracrine growth factor for these cells via the IGF 1 receptor . ^^^ These results suggest that insulin via the IGF 1 receptor or insulin receptor can function as an autocrine or paracrine growth factor in these T ALLs . ^^^ Proliferation of the most differentiated T ALL Jurkat and JMP was inhibited only by alpha IR 3 and 2C2 , an antibody directed against the IGF 2 receptor , suggesting that IGF 1 or IGF 2 acting via the IGF 1 receptor or IGF 2 receptor may be involved in proliferation of these cell lines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed that 2 , 3 , 7 , 8 TCDD did not alter the IGF 1 receptor mRNA levels or the KD values for binding of [ 125I ] IGF 1 to the IGF 1 receptor in MCF 7 cells . ^^^ However , 2 , 3 , 7 , 8 TCDD significantly decreased the number of IGF 1 induced IGF 1 receptor binding sites and this may play a role in the growth inhibitory properties of 2 , 3 , 7 , 8 TCDD and related compounds and in the ' cross talk ' between the two endocrine response pathways . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In particular , we used antisense oligodeoxynucleotides to study : ( 1 ) the role of the IGF 1 receptor in the control of cell proliferation ; and ( 2 ) the sequence of gene expression during the cell cycle . ^^^ Our results can be summarized as follows : ( 1 ) the activation of the IGF 1 receptor by its ligand , IGF 1 , is an obligatory step in the proliferation of fibroblasts and hemopoietic cells ; and ( 2 ) the expression of DNA synthesis genes , such as PCNA , DNA polymerase alpha , and cdc 2 , is dependent on the expression of previous genes . ^^^ A tentative temporal order is : c myc > c myb > IGF 1 receptor > DNA synthesis genes . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It has also been reported that the actions of both peptides are mediated through the IGF 1 receptor . ^^^ However , MCF 7 cells were stimulated 4 5 fold with IGF 1 and insulin , while IGF 2 was only slightly less potent . alpha IR 3 , a monoclonal antibody directed against the IGF 1 receptor , was stimulatory when added alone . ^^^ These data suggest that alpha IR 3 and IGF 1 are acting as agonists through the IGF 1 receptor , but that insulin and IGF 2 are acting through other receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These data demonstrated a 135 , 000 Mr peptide that specifically binds radiolabeled IGF 1 and corresponds to the alpha subunit of the type 1 IGF IR , and a 260 , 000 Mr peptide that specifically binds radiolabeled IGF 2 and corresponds to the type 2 IGFR . ^^^ We have additionally found that IGF 1 and IGF 2 ( in nanomolar concentrations ) produce as much as a threefold enhancement of T cell proliferation early in the activation process , correlating with the early appearance of IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Gene expression of insulin like growth factor 1 and IGF 1 receptor during wound healing in rats . ^^^ OBJECTIVE To measure the time course of changes in the concentrations of insulin like growth factor 1 ( IGF 1 ) , IGF 1 messenger RNA ( mRNA ) , and IGF 1 receptor mRNA during wound healing . ^^^ MAIN OUTCOME MEASURES Wet weight and concentrations of IGF 1 mRNA , and IGF 1 receptor mRNA of granulation tissue , and concentration of IGF 1 in wound fluid . ^^^ The concentration of IGF 1 receptor RNA remained constant throughout the study , and the concentration of IGF 1 in wound fluid remained constant until week 8 and then increased to a higher level at weeks 11 18 . ^^^ CONCLUSION There is a transient rise in the gene expression of IGF 1 but not of IGF 1 receptor mRNA during wound healing . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using the antisense strategy and the reverse transcriptase polymerase chain reaction ( RT PCR ) , we show that expression of the IGF 1 receptor is required for the entry into S phase of both stimulated lymphocytes and HL 60 cells . ^^^ The inhibition of DNA synthesis by antisense oligomers to the IGF 1 receptor RNA is accompanied by an inhibition of the expression of the mRNA for a DNA synthesis gene , proliferating cell nuclear antigen ( PCNA ) , the co factor of DNA polymerase delta . ^^^ Inhibition of c myb expression results in a decrease in IGF 1 receptor mRNA levels ; on the other hand , inhibition of IGF 1 receptor expression has no effect on c myb mRNA levels . ^^^ A tentative temporal relationship between these three genes ( c myb , IGF 1 receptor , PCNA ) is proposed . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Growth hormone and prolactin stimulate androgen receptor , insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor levels in the prostate of immature rats . ^^^ Quantitative analysis of RNAs shows that treatment with either PRL or GH increases significantly steady state mRNAs levels of the following genes in the prostate : androgen receptor ( AR ) ( respectively 3 . 5 and 4 . 8 fold above hypox controls ) , IGF 1 ( 5 and 2 . 7 fold ) , and IGF 1 receptor ( 2 . 9 and 2 . 3 fold ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Also , DTaI can competitively displace [ 125I ] insulin with an ED 50 of 1 . 1 10 10 ( 8 ) M , which is identical to the ED 50 of insulin ( 1 . 1 10 10 ( 8 ) M ) and showed limited cross reactivity with the IGF 1 receptor ( 12 % displacement of [ 125I ] IGF 1 with a DTaI concentration of 1 . 1 10 10 ( 8 ) M ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
T 3 treatment induced a large increase in the intensity of bands migrating at 135K and 280K , representing the alpha subunit of the IGF 1 receptor and an incompletely reduced alpha alpha dimer , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression during experimental demyelination and myelin regeneration , young mice were fed cuprizone ( ( bis ( cyclohexanone ) oxaldihydrazone ) ) . ^^^ At intervals during cuprizone treatment and recovery , brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF 1 and IGF 1 receptor mRNAs and peptides . ^^^ In untreated littermates , IGF 1 and IGF 1 receptor mRNAs and peptides were not detected in white matter . ^^^ In severely demyelinated areas , immature oligodendroglia exhibited a transient increase in IGF 1 receptor mRNA and peptide immunoreactivity during early recovery . ^^^ This highly specific pattern of IGF 1 induction in astrocytes during demyelination and the expression of the IGF 1 receptor in regenerating oligodendrocytes during recovery suggest that IGF 1 functions in the regulation of oligodendrocyte and myelin metabolism in vivo . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of the IGF 1 receptor in the regulation of cdc 2 mRNA levels in fibroblasts . ^^^ In p 6 cells , which constitutively overexpress the IGF 1 receptor , IGF 1 is sufficient . ^^^ The importance of the IGF 1 / IGF 1 receptor interaction in regulating the levels of cdc 2 mRNA was further confirmed by showing that an antisense oligodeoxynucleotide to the IGF 1 receptor RNA inhibited the IGF 1 mediated increase . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , incubation of bovine fibroblasts with IGFBP 3 had modifying effects on type 1 IGF receptor mediated signalling because 1 ) the bioeffectiveness of [ Gln 3 , Ala 4 , Tyr 15 , Leu 16 ] IGF 1 and insulin , IGF 1 receptor activators with little or no affinity for IGFBP 3 , was potentiated by preincubation with IGFBP 3 ; and 2 ) fibroblast responsiveness to IGF 1 analogs with different affinities for the type 1 IGF receptor was enhanced in direct relation to the ability of the peptide to bind to the receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Anatomical relationships in the patterns of insulin like growth factor ( IGF ) 1 , IGF binding protein 1 , and IGF 1 receptor gene expression in the rat kidney . ^^^ In order to identify which renal structures produce IGF 1 and the functionally related IGF binding protein 1 ( IGFBP 1 ) , and which structures are potential sites of circulating or endogenous renal IGF action , we have employed in situ hybridization to localize IGF 1 , IGFBP 1 , and IGF 1 receptor messenger RNAs ( mRNAs ) in the rat kidney . ^^^ The effects of hypophysectomy ( Hx ) and GH replacement on renal IGF 1 , IGFBP 1 , and IGF 1 receptor gene expression have also been evaluated . ^^^ IGF 1 receptor mRNA is also abundant in TALs , but , in addition , is distributed throughout the distal nephron and collecting duct , and in the glomerulus , with lowest levels found in proximal tubules . ^^^ In general , Hx resulted in decreased IGF 1 and increased IGFBP 1 mRNA levels , and GH treatment produced the opposite effects , while IGF 1 receptor mRNA levels were not significantly effected by either treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These antibodies promise to be valuable tools in resolving issues of IGF 1 receptor heterogeneity and in studying the structure and function of classical type 1 receptors and insulin / IGF receptor hybrids . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 2 gene is thus expressed at high levels in the mesenchymal stroma of the decidua to establish potentially short range communication with primarily IGF 1 receptor positive mesenchymal stroma cells . ^^^ Conversely , the glandular and surface epithelia coexpress the IGF 1 receptor and IGF 1 genes , while the IGF 2 gene is not detected above background levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of IGF 1 on IGFBP 2 levels and the synergistic action of IGF 1 and RA on IGFBP 3 levels in CM were blocked by alpha IR 3 , a monoclonal antibody to the human IGF 1 receptor , indicating that these effects required signal transduction through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have used in situ hybridization to test whether this inductive activity correlates with the developmental expression of genes encoding insulin like growth factors 1 and 2 ( IGF 1 and 2 ) and / or proteins that may mediate IGF action ( IGF binding protein 2 and the IGF 1 receptor ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Despite the presence of insulin like growth factor 1 ( IGF 1 ) to substitute for supraphysiological concentrations of insulin and to saturate IGF 1 receptor , GH was still required to induce terminal differentiation of a maximal number of cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 inhibition of GH secretion is enhanced 3 5 fold in GC rat pituitary cells overexpressing the wild type 950Tyr human IGF 1 receptor which autophosphorylates appropriately . ^^^ To determine the critical amino acid sequence responsible for IGF 1 signaling , insertion , deletion , and site directed mutants were constructed to substitute for 950Tyr in exon 16 of the human IGF 1 receptor beta subunit transmembrane domain . ^^^ All mutant transfectants , except the deletion mutant , internalized radioactive ligand similarly to 950Tyr wild type transfectants . 950Tyr of the human IGF 1 receptor is therefore required for IGF 1 signal transduction in the pituitary somatotroph , but not for IGF 1 mediated internalization . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We show that BALB 58 cells , at 34 degrees C , have a markedly increased expression of IGF 1 and IGF 1 mRNA and that their growth in 1 % serum ( at 34 degrees C ) is inhibited by an antisense oligodeoxynucleotide to the IGF 1 receptor RNA . ^^^ When this tsA plasmid is stably transfected into cells constitutively overexpressing the human IGF 1 receptor cDNA , the resulting cell lines show a constitutively phosphorylated IGF 1 receptor and grow in serum free medium at 34 degrees C ( but not at 39 . 6 degrees C ) . ^^^ We conclude ( 1 ) that the SV 40 T antigen induces the expression of IGF 1 and IGF 1 mRNA , at least in part by a transcriptional mechanism , thus altering the growth factors requirements , and ( 2 ) that , in BALB / c3t3 cells , the SV 40 T antigen necessitates a functional IGF 1 receptor for its growth stimulating effect in low serum ( or PDGF ) . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that insulin ( probably through the IGF 1 receptor ) and IGF 1 modulate the levels of TTF 2 , which results in an increased expression of the Tg gene . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An analysis of the processes involved revealed that progestins increased the biosynthesis of a ligand for IGF 1 receptor , IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In view of results suggesting that IGF 1 is a more potent mitogen than estradiol for breast cancer cells and data demonstrating a positive correlation between estrogen receptor level and IGF 1 receptor level of breast cancer cells , the IGF 1 lowering effect of tamoxifen may contribute to the cytostatic activity of the drug . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These analogues were able to inhibit the autophosphorylation of the IGF 1 receptor as well as the growth of several different cell types , including prostate carcinoma cells and SV 40 transformed cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Rat somatotroph insulin like growth factor 2 ( IGF 2 ) signaling : role of the IGF 1 receptor . ^^^ Fifty percent competition for [ 125I ] IGF 1 binding by IGF 1 and IGF 2 in GC rat pituitary cells demonstrated a 14 fold lesser affinity of the IGF 2 ligand for the IGF 1 receptor compared to IGF 1 ; therefore , the binding affinity of IGF 2 for the IGF 1 receptor correlates with the concentration of IGF 2 required for 50 % GH inhibition . ^^^ In contrast , cells transfected with a truncated IGF 1 receptor cDNA lacking the cytoplasmic receptor beta subunit ( 952STOP ) failed to transduce the IGF 2 signal , indicating that functional IGF 1 receptors are required for IGF 2 signaling . ^^^ In addition , a mutant IGF ligand , [ Leu 27 ] IGF 2 , which selectively exhibits high affinity for the type 2 receptor , but only minimal binding to the IGF 1 receptor , did not attenuate GH secretion . ^^^ However , the analog [ Arg 54 , Arg 55 ] IGF 2 , which exhibits high affinity to the IGF 1 receptor , but no binding to the type 2 receptor , appropriately suppressed GH secretion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This coincided with a reciprocal 25 % decrease in IGF 1 receptor mRNA content and a 40 % decrease in total 125I IGF 1 binding . ^^^ After denudation there was a relative decrease in IGF 1 receptor mRNA in the medial cells as compared to the neointima , suggesting that the site of IGF 1 action was predominantly in the medial layer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Hybrid receptors were studied in GC rat pituitary cells overexpressing either wild type 950Tyr ( WT ) human insulin like growth factor 1 ( IGF 1 ) receptors or mutant human IGF 1 receptors truncated at position 952 in the beta subunit transmembrane region ( 952STOP ) . 125I IGF 1 binding was increased in both 950Tyr ( WT ) ( 14 fold ) and truncated human IGF 1 receptor ( 952STOP ) stable transfectants ( 50 fold ) , when compared to untransfected cells that contained endogenous rat IGF 1 receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effects of tri iodothyronine and insulin like growth factor 1 ( IGF 1 ) on alkaline phosphatase activity , [ 3H ] thymidine incorporation and IGF 1 receptor mRNA in cultured rat epiphyseal chondrocytes . ^^^ The effects of tri iodothyronine ( T 3 ) and insulin like growth factor 1 ( IGF 1 ) on [ 3H ] thymidine incorporation , alkaline phosphatase ( ALP ) activity and IGF 1 receptor mRNA levels were studied in rat epiphyseal chondrocytes cultured in monolayer . ^^^ After preculture the medium was changed to Ham ' s F 12 medium containing 1 % ( v / v ) serum from hypophysectomized rats , and the effects of T 3 and / or IGF 1 on DNA synthesis ( [ 3H ] thymidine incorporation ) , ALP activity ( a late marker of differentiated epiphyseal chondrocytes ) and IGF 1 receptor mRNA levels were studied . ^^^ Furthermore , IGF 1 receptor mRNA levels were increased by 10 micrograms T3 / l ( 137 + / 4 . 2 % compared with control culture ) while no effect of hGH ( 50 micrograms / l ) or IGF 1 ( 25 micrograms / l ) was demonstrated . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibition of IGF 1 action by circulating IGF 1 receptor autoantibodies is a potential mechanism of IGF 1 resistance in growing children . ^^^ To define the prevalence of IGF 1 receptor antibodies in short statured children , we have examined serum and plasma samples from a well characterized group of 34 short , prepubertal , growth hormone sufficient children and three growth hormone deficient children . ^^^ IGF 1 receptor purified from human placental membranes was radioiodinated by the solid phase radioiodination method . ^^^ Serum from a patient with severe insulin resistance immunoprecipitated 28 . 9 44 . 7 % of the 125I labeled IGF 1 receptor . ^^^ The ranges ( mean + / 3 SD ) of 125I labeled IGF 1 receptor immunoprecipitated by 1 : 10 diluted and by undiluted nonimmune human serum were 1 . 99 + / 0 . 63 % and 4 . 42 + / 1 . 32 % , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGFs act through two types of specific membrane receptors : the so called `` type 1 ' ' or IGF 1 receptor , and the `` type 2 ' ' or IGF 2 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Diabetes induces feto placental overgrowth , but it is not known whether it modifies IGF 1 receptor activity in fetal and / or placental tissues . ^^^ In rats made hyperglycaemic and insulinopenic by streptozotocin injection on day 1 of pregnancy , placental IGF 1 receptor binding parameters were not different from controls on day 20 of pregnancy . ^^^ The present study indicates that the rat placental IGF 1 receptor possesses structural characteristics similar to that reported for fetal rat muscle , and suggests that the high molecular mass beta subunit could represent a type of receptor specifically expressed during prenatal development . ^^^ In addition , it clearly demonstrates that diabetes induces functional alterations in IGF 1 receptor kinase activity that may play a major role in the placental overgrowth in diabetic pregnancy . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to illuminate potential interactions between GH and insulin like growth factor 1 ( IGF 1 ) in regulating renal function , we compared the anatomical localization of GHR messenger RNA ( mRNA ) with that for the IGF 1 receptor and for IGF 1 in the rat kidney . ^^^ In contrast , IGF 1 receptor mRNA was concentrated in the glomerulus , distal nephron and collecting system . ^^^ The only point of convergence for GHR and IGF 1 receptor mRNAs was in the MTAL , where IGF 1 mRNA was localized . ^^^ This segregation of GHR and IGF 1 receptor gene expression in the kidney suggests that each hormone has distinct spheres of action along the nephron , with GH acting directly on the proximal straight tubule , whereas IGF 1 may act on the glomerulus , distal nephron , and collecting duct . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The abundance of insulin receptor mRNA exceeded that for IGF 1 receptor mRNA in liver and yolk sac at all times studied . ^^^ This difference was greater in liver , where insulin receptor mRNAs were three to more than 50 times more abundant than IGF 1 receptor mRNA on gestation days E 13 E16 , times which antedate the development of significant hepatic metabolic actions of insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the mouse , IGF 2 ligand and receptor mRNAs were not expressed until the 2 cell stage , and the insulin and IGF 1 receptor mRNAs were not detectable until the 8 cell stage . ^^^ Colloidal gold immunocytochemistry with antibodies directed against the insulin receptor , IGF 1 receptor and IGF 1 ligand has confirmed the presence of these molecules in bovine blastocysts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin stimulated PDH activity 3 4 fold in cells that overexpressed normal human insulin receptors , but not in cells expressing TMI receptors , composed of the ligand binding domain of the insulin receptor coupled to the transmembrane and intracellular components of the IGF 1 receptor , or CEX receptors , in which the carboxy terminal 110 amino acid portion of the insulin receptor was exchanged for the corresponding portion of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of continuous or acute administration of insulin or insulin like growth factor 1 ( IGF 1 ) on IGF 1 mRNA and IGF 1 receptor mRNA were studied in the skeletal muscle ( gastrocnemius ) , heart muscle and vascular smooth muscle ( aorta ) of non diabetic and diabetic rats using a solution hybridization assay . ^^^ The levels of IGF 1 mRNA in the different types of muscle markedly decreased by diabetes , whereas changes in IGF 1 receptor mRNA were less consistent . ^^^ Continuous infusion of diabetic rats with insulin ( 28 or 35 nmol / day ) for 4 days normalized the altered levels of IGF 1 mRNA and IGF 1 receptor mRNA . ^^^ Infusion of equimolar concentrations of IGF 1 did not affect IGF 1 mRNA , but decreased the level of IGF 1 receptor mRNA in skeletal muscle . ^^^ Insulin did not significantly affect levels of IGF 1 mRNA , but decreased levels of IGF 1 receptor mRNA in skeletal muscle and aorta . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , a monoclonal antibody to the IGF 1 receptor suppressed DNA synthesis when determined by a [ 3H ] thymidine incorporation assay . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Responses of both growth factors were measured in the presence and absence of alpha IR 3 , and IGF 1 receptor blocking antibody . ^^^ The significant inhibition of growth responses to high concentrations of insulin and to IGF 1 by alpha IR 3 suggests mediation of these effects through the IGF 1 receptor . ^^^ Thus , both insulin and IGF 1 receptor effector mechanisms are involved in the growth of virally transformed T lymphoblasts , whereas the IGF 1 receptor effector mechanism appears to play a more significant role in the growth of normal , mitogen activated T lymphocytes . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Upon preincubation with IGF 1 , 97 / 90K polypeptides were phosphorylated , corresponding to the IGF 1 receptor beta subunits , and were immunoprecipitated with both PY 20 and anti IGF 1 receptor antibodies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The temporal patterns of endometrial expression for mRNAs encoding insulin like growth factor 1 ( IGF 1 ) , IGF 2 , IGF binding protein 2 ( IGFBP 2 ) , and the type 1 IGF receptor ( IGF IR ) were elucidated in cyclic and pregnant pigs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Finally , we found that IGF 1 and insulin , probably acting through the IGF 1 receptor , increase GLUT 1 expression and stimulate glucose transport activity in epidermis reconstituted in culture . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
All these effects were achieved with EC50s of approximately 60 pM IGF 1 , which is in the range for IGF 1 receptor mediation ; however , cross reaction with insulin , IGF 2 , or other unknown receptors is not excluded . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate a possible link between the effects of oestradiol and IGF 1 , a specific IGF 1 receptor antibody ( alpha IR 3 ) , 10 micrograms / ml was used . ^^^ This synergistic effect on the IGF 1 growth response was totally abolished by the IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tertiary structure similarities further explain the interactions of each ligand with the heterologous receptor ; thus insulin receptors bind insulin with high affinity and IGF 1 with lower affinity , and the opposite is true for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , yisoIGF 1 demonstrated a severely reduced ability to bind to the IGF 1 receptor ( 19 % ) and was less potent in provoking a mitogenic response in Balb / C 3T3 fibroblasts ( 50 % at doses 10 100 ng / ml ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) reduced ChAT activity at concentrations 10 fold lower than insulin , suggesting that insulin ' s effect on ChAT may involve the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 stimulated at concentrations consistent with its acting through the IGF 1 receptor ; however , insulin stimulated at concentrations higher than expected for its acting through its receptor and this its action may be mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , chimeric receptors containing exon 3 of the IGF IR could also bind with high affinity both IGF 1 and IGF 2 . ^^^ These results indicate that ( 1 ) the high affinity of binding of insulin to its receptor can occur in the absence of insulin receptor specific residues encoded by exon 3 , the cysteine rich region ; ( 2 ) the cysteine rich region of the IGF 1 receptor can confer high affinity binding to both IGF 1 and IGF 2 ; and 3 ) the IRR is unlikely to be a receptor for either IGF 1 , IGF 2 , or relaxin . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Phosphorylation of both p 175 and receptors exhibited almost identical time courses and insulin dose responses , suggesting that p 175 may serve as a substrate for the insulin and IGF 1 receptor kinases . ^^^ Thus , a receptor phosphatase activity from insulin stimulated FRTL 5 cells is retained on an antiphosphotyrosine affinity matrix and correlates with phosphorylation of the p 175 substrate for the insulin and IGF 1 receptor kinases . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In CSV 3 1 cells insulin appears to act on its own receptor rather than on the IGF 1 receptor , because at comparable dosages IGF 1 is 10 to 100 fold less effective than insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
AM expressed IGF II / M6P receptors as detected by [ 125 ] IGF 2 surface binding that was not reduced by recombinant IGF 1 or IGF 1 receptor monoclonal antibody ( alpha IR 3 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Receptor studies revealed a similar binding capacity for des IGF 1 and IGF 1 to the IGF 1 receptor ( s ) in Ob cells , although at 0 . 2 nM des IGF 1 was slightly more effective than IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expression of mRNAs encoding insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor in the developing rat brain from embryonic day 16 to postnatal day 82 was analyzed using solution hybridization RNase protection assays . ^^^ In contrast , IGF 1 receptor gene expression did not exhibit any region specific developmental changes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and insulin like growth factor 1 ( IGF 1 ) initiate their metabolic , growth , and differentiation effects through binding to the insulin receptor and the IGF 1 receptor , two members of the tyrosine kinase family of receptors . ^^^ To study the role of these peptides and receptors in early development , we used the polymerase chain reaction and embryo derived RNA to generate partial cDNA sequences of the insulin receptor and IGF 1 receptor from the amphibian Xenopus laevis . ^^^ The third sequence , XTK 2 , corresponds to a peptide that has 92 % amino acid identity with the human IGF 1 receptor but only 80 % identity with XTK 1a and XTK 1b . ^^^ On the basis of these similarities , the pattern of conserved amino acids , and the tetraploid nature of the Xenopus genome , we suggest that XTK 1a and XTK 1b most likely represent the product of two different nonallelic insulin receptor genes , while XTK 2 may be one of the probable two Xenopus IGF 1 receptor genes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Fibroblast growth factor inhibits insulin like growth factor 2 ( IGF 2 ) gene expression and increases IGF 1 receptor abundance in BC3H 1 muscle cells . ^^^ We have previously reported that muscle cell differentiation is associated with down regulation of the IGF 1 receptor at the level of gene expression that is concomitant with an increase in the expression and secretion of IGF 2 . ^^^ Furthermore , treatment of myoblasts with IGF 2 resulted in a similar decrease in IGF 1 receptor mRNA abundance , suggesting an autocrine role of IGF 2 in IGF 1 receptor regulation . ^^^ To explore further the role of IGF 2 in IGF 1 receptor regulation , BC3H 1 mouse muscle cells were exposed to differentiation medium in the presence of basic fibroblast growth factor ( FGF ) , a known inhibitor of myogenic differentiation . ^^^ Scatchard analyses and studies of gene expression demonstrated that the increased IGF 1 binding induced by FGF reflected parallel increases in IGF 1 receptor content and mRNA abundance . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Treatment of T47D cells with either progesterone or the synthetic progestin promegestone ( R 5020 ) decreased IGF 1 receptor content by approximately 50 % , as measured by Scatchard analysis and receptor biosynthesis studies . ^^^ In contrast to progestins , estradiol , dexamethasone , and dihydrotestosterone did not influence IGF 1 receptor content . ^^^ R 5020 decreased IGF 1 receptor mRNA abundance , indicating that progestins acted at the level of gene expression . ^^^ However , progestins also increased the secretion of IGF 2 , a ligand for the IGF 1 receptor . ^^^ The addition of exogenous IGF 2 to T47D cells down regulated both IGF 1 receptor binding and IGF 1 receptor mRNA abundance . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This conclusion is supported by the following observations . 1 ) Myogenin mRNA is elevated by IGF 1 , with a concentration dependency that parallels the stimulation of differentiation , including a decrease in stimulation at higher concentrations . 2 ) The time course of elevation of myogenin mRNA is consistent with its acting as an intermediate in the signalling pathway between occupancy of the IGF 1 receptor and induction of expression of muscle specific genes . 3 ) Inhibitors of myogenesis also inhibit elevation of myogenin mRNA in response to IGF 1 . 4 ) An antisense oligonucleotide to the N terminus of myogenin prevents the stimulation of differentiation by IGF 1 and IGF 2 , but has no effect on other actions of IGF 1 on myoblasts . ^^^ However , the relatively long time period between addition of the IGFs and elevation of myogenin mRNA as well as the inhibition of this process by several inhibitors indicate that increased myogenin mRNA levels are not a simple direct result of occupation of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A radioimmunoassay for the human insulin like growth factor 1 ( IGF 1 ) receptor was developed using a rabbit polyclonal antibody to the human IGF 1 receptor and a highly purified IGF 1 receptor . ^^^ Purified IGF 1 receptor concentrations as low as 5 ng / 0 . 5 mL inhibited the radiolabeled IGF 1 receptor binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The radioimmunoassay was sensitive ( limit of detection less than 17 fmol ) , reproducible ( inter and intra assay coefficients of variation 12 . 5 % and 1 . 6 % respectively ) and specific ( no crossreactivity with pure placental IGF 1 receptor , insulin and glucagon ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , a monoclonal antibody ( MoAb ) directed against the human IGF 1R ( alpha IR 3 ) inhibited IGF 1 but not IL 3 induced proliferation and these cells contained 20 to 200 fold more IGF 1 receptors than uninfected FDC P 1 cells . ^^^ These results demonstrate that IGF 1 can replace IL 3 for growth when FDC P 1 cells overexpress the IGF 1R . ^^^ Growth promoting effects of insulin like growth factor 1 ( IGF 1 ) on hematopoietic cells : overexpression of introduced IGF 1 receptor abrogates interleukin 3 dependency of murine factor dependent cells by a ligand dependent mechanism . ^^^ To further examine the effects of IGF 1 on hematopoietic cells , FDC P 1 cells were infected with a retroviral construct ( LISN ) containing the human IGF 1 receptor ( hIGF 1R ) and neo genes . ^^^ Given the fairly ubiquitous expression of the IGF 1 receptor , these and additional experiments might help to determine whether increased expression of endogenous receptors by cells can lead to leukemogenesis and tumorigenesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
They exert their mitogenic effects by binding to the IGF 1 receptor and activating its tyrosine protein kinase . ^^^ This effect is inhibited by antibodies directed against the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The presence of the IGF 1 receptor messenger RNA and IGF 1 receptor as well as the role of IGF 1 in the amplification of gonadotropin action in luteinized rat ovarian cells were assessed in the present study . ^^^ Binding studies performed with ovarian luteal cell membranes in the ovary revealed a dissociation constant of 0 . 94 nM for the IGF 1 receptor . ^^^ Northern blot analysis showed the presence of a major transcript at approximately 11 kilobases , which agrees with the size of the IGF 1 receptor messenger RNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PMA stimulated phosphorylation of a single major IGF 1 receptor phosphoserine peptide which was phosphorylated to a lesser extent after IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Covalent cross linking followed by SDS PAGE analysis demonstrated a radioactive band of Mr 135 , 000 which corresponds to the alpha subunit of the IGF 1 receptor . ^^^ Solution hybridization / RNase protection assay produced a single protected band corresponding to IGF 1 receptor messenger RNA , further confirming the presence of these receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Identification and in situ localization of the insulin like growth factor II / mannose 6 phosphate ( IGF II / M6P ) receptor in the rat gastrointestinal tract : comparison with the IGF 1 receptor . ^^^ In the present study we investigated pharmacological , biochemical , and immunological characteristics as well as the tissue distribution of the insulin like growth factor II / mannose 6 phosphate ( IGF II / M6P ) receptor in the rat gastrointestinal tract , and compared the data with those from corresponding experiments for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that replacement of the amino terminal 137 amino acids of the insulin receptor ( IR ) with the corresponding 131 amino acids of the IGF 1 receptor ( IGF 1R ) resulted in loss of affinity for both ligands . ^^^ Further replacement of the adjacent cysteine region with IGF 1R sequences fully reconstituted affinity for IGF 1 , but only marginally for insulin . ^^^ Unexpectedly , replacement of the IR cysteine rich domain alone by IGF 1R sequences created a high affinity receptor for both insulin and IGF 1 . ^^^ Our chimeric receptor data , in conjunction with IR amino terminal domain point mutants , strongly suggest major contributions of structural determinants in both amino and carboxyl terminal IR alpha subunit regions for the formation of the insulin binding pocket , whereas , surprisingly , the residues defining IGF 1 binding are present predominantly in the cysteine rich domain of the IGF 1R . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The increased expression of IGF 1 receptor mRNA also results in an increased number of IGF 1 binding sites per cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The design , expression , and characterization of human insulin like growth factor 2 ( IGF 2 ) mutants specific for either the IGF II / cation independent mannose 6 phosphate receptor or IGF 1 receptor . ^^^ Five mutants of recombinant insulin like growth factor 2 ( rIGF 2 ) that bound with high affinity to either the IGF II / cation independent mannose 6 phosphate ( IGF II / CIM6 P ) or the IGF 1 receptor were prepared by site directed mutagenic procedures , expressed as fusion proteins in the larva of Bombyx mori or Escherichia coli , purified to homogeneity , renatured , and characterized in terms of their receptor binding affinities and specificities as well as their biological activities . ^^^ In two biological assay systems , i . e . the stimulation of DNA synthesis in Balb / c 3T3 cells and glycogen synthesis in HepG 2 cells , the Kd ( app ) of the rIGF 2 mutants for the IGF 1 receptor but not the IGF II / CIM6 P receptor correlated with their abilities to produce biological responses . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These effects of PGF 2 alpha on IGF 1 receptor number and IGFBP secretion may play a role in the synergism between PGF 2 alpha and IGF 1 that results in the stimulation of DNA synthesis in MC3T3 E 1 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We , therefore , isolated neomycin resistant stable GC cell transfectants over expressing human IGF 1 receptor cDNA ( IGFIR cDNA ) cloned in an Rous sarcoma virus directed expression vector . ^^^ Immunoprecipitation of metabolically labeled [ 35S ] methionine stably transfected cells revealed a 200 kDa human IGF 1 receptor precursor protein . ^^^ These results demonstrate that transfectants overexpressing human IGF 1 receptor are hyperresponsive to exogenous IGF 1 . ^^^ These data indicate that IGF 1 receptor number plays an important role in mediating the signal transduction of IGF 1 to the GH gene . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using the ribonuclease protection assay , we found that hCG and 8 bromo cAMP could increase IGF 1 receptor mRNA expression as early as 2 h before the increase in IGF 1 binding . ^^^ The induction by hCG was over 3 . 5 fold at 4 h and decreased to about 2 fold at 6 h . 4 beta Phorbol 12 beta myristate 13 alpha acetate had a very small effect on IGF 1 receptor mRNA levels ( 1 . 5 fold increase at 2 h and no changes at 4 and 6 h ) . ^^^ The up regulation of IGF 1 receptor number is associated with transient increases in IGF 1 receptor mRNA levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression , action , and steroidal regulation of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor in the rat corpus luteum : their differential role in the two cell populations forming the corpus luteum . ^^^ The overall aim of this investigation was to examine the expression and steroidal regulation of insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor in the rat corpus luteum and to examine the specificity of IGF 1 action in the two luteal cell populations . ^^^ We first examined whether the corpus luteum expresses the IGF 1 and IGF 1 receptor genes . ^^^ Using a solution hybridization / RNase protection assay , IGF 1 and IGF 1 receptor mRNAs were represented by protected bands 224 and 265 bases in length , respectively . ^^^ In addition , Northern blot analysis showed that , as in liver , rat IGF 1 and IGF 1 receptor cDNAs hybridized with 7 . 5 , 1 . 8 , and 0 . 8 to 1 . 2 kilobase transcripts and an 11 kilobase transcript , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results of these experiments established that 1 ) hIGF 2 and appMr 15 , 000 hIGF 2 bind to the IGF 1 receptor with the same affinity as rIGF 1 , e . g . with Kd and Ki values between 0 . 03 0 . 07 nM ; 2 ) the total binding capacity , i . e . ^^^ Measurements of the stimulation of IGF 1 receptor autophosphorylation at low ligand concentrations established that appMr 15 , 000 hIGF 2 and hIGF 2 were more effective than rIGF 1 in coupling receptor occupancy to the activation of its protein kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cellular pattern of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression in the developing and mature ovarian follicle . ^^^ We have employed in situ hybridization histochemistry to map the cellular pattern of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression in developing rat ovaries from the time of birth through adulthood , and in response to hypophysectomy and gonadotropin replacement . ^^^ From the early postnatal period , both IGF 1 and IGF 1 receptor messenger RNAs ( mRNAs ) were highly abundant and evenly distributed in granulosa cells of small , growing follicles . ^^^ IGF 1 receptor mRNA was evenly distributed in developing and mature follicles and was highly abundant in the luteinized granulosa cells of corpora lutea . ^^^ IGF 1 receptor but not IGF 1 mRNA was detected in growing oocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding of both hormones to their own receptors was highly specific as compared with binding to the respective other receptor ( insulin receptor : KD = 3 . 6 nM , KI of IGF 1 greater than 500 nM ; IGF 1 receptor , KD = 1 . 1 nM , KI of insulin = 191 nM ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Competition studies revealed [ 125I ] IGF 1 binding within the SCN and ME to have the pharmacological specificity characteristic of the brain IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both the basal growth rate in the absence of metal ions and the Zn2+ induced increases in cell proliferation could be inhibited by the monoclonal antibody alpha IR 3 , which blocks the binding site of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Chem . 264 , 9994 10001 ] that polylysine had no effect on the IGF 1 receptor TPK despite its 84 % identity to the insulin receptor TPK . ^^^ We report that the IGF 1 receptor TPK is stimulated by polycations and basic proteins in a manner similar to their effects on the insulin receptor TPK . ^^^ When effects of polylysine and polyarginine on both receptor TPKs were closely compared , subtle qualitative differences were found : Polylysine stimulated autophosphorylation and exogenous substrate phosphorylation activities of both insulin receptor TPK and IGF 1 receptor TPK similarly . ^^^ In contrast , another polycation , polyarginine , affected both TPKs in a manner quite different from polylysine : Polyarginine stimulated insulin receptor autophosphorylation to a greater extent than polylysine did while it had a very small effect on the IGF 1 receptor autophosphorylation as well as the exogenous substrate phosphorylation activities of the two receptor TPKs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The presence of the IGF 1 receptor and the absence of IGF 2 and insulin receptors are discussed in relation to the capacity of PA 3 cells to produce bone lesions on the L W rat . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using partially purified receptors we show that hormone stimulated insulin receptors induced a 40 % increase in IGF 1 receptor phosphorylation . ^^^ Remarkably , this transphosphorylation of IGF 1 receptors by insulin receptors resulted in a 2 . 5 fold augmentation of the IGF 1 receptor tyrosine kinase activity for substrates . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition to enhancing insulin and IGF 1 receptor autophosphorylation , all 3 peptides stimulate the tyrosine phosphorylation of a 70 kDa protein with a similar time course and dose response to receptor phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate possible changes in IGF 1 receptor binding sites in brain tissue of patients with these pathological conditions , the binding of [ 125I ] IGF 1 was determined in tissues obtained from control , Alzheimer ' s and / or patients with a history of alcoholism . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Pretreatment of the cells with EGF , concomitantly with IGF 1 , had no effect on [ 125I ] IGF 1 binding but it augmented the IGF 1 down regulation of IGF 1 receptor . ^^^ The time required to initiate the IGF 1 induced down regulation of IGF 1 receptor was reduced by 4 h in the presence of EGF . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An altered IGF 1 receptor is present in human leukemic cells . ^^^ Binding of 125I IGF 1 to partially purified plasma membrane proteins followed the characteristics of IGF 1 receptor binding . 125I IGF 1 binding , as determined by chemical cross linking , occurred to a 145 kDa protein . ^^^ Phosphorylation of pp 105 followed the dose response characteristics of the IGF 1 receptor . ^^^ These data suggest that pp 105 is the beta subunit of an IGF 1 receptor variant with a higher molecular weight , similar to that found in fetal tissue . ^^^ The HL 60 cell may acquire , at least in part , malignant growth characteristics through reexpression of the fetal version of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin stimulated a fourfold increase in release of the 24 , 000 Mr protein while inhibiting IGF BP 1 release comparable to IGF 1 , alpha IR 3 , a monoclonal antibody to the IGF 1 receptor , blocked approximately 33 % of the IGF 1 response but had no effect on insulin mediated IGF BP 1 inhibition . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , at concentrations of IGF 1 that caused maximal phosphorylation of the IGF 1 receptor , no displacement of insulin binding was observed . 2 . ^^^ In contrast , no increased phosphorylation of IGF 1 receptor was observed in cells treated with 100 ng of insulin / ml . 3 . ^^^ The increase in phosphorylation of insulin receptor in response to IGF 1 correlated with the dose response of IGF 1 stimulated phosphorylation of the IGF 1 receptor . 4 . ^^^ The IGF 1 stimulated phosphorylation of the insulin receptor could be blocked by preincubation with a monoclonal antibody that blocks IGF 1 binding to the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Conversely , endogenous insulin receptors in NIH 3T3 cells were unreactive with anti ( IGF 1 receptor ) antibodies alpha IR 3 and 16 13 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These data suggest that soluble bIGFBP 3 inhibits IGF 1 action by sequestering and preventing IGF 1 receptor binding , whereas surface associated bIGFBP 3 enhances the growth promoting effects of IGF 1 in bovine fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The data indicate IGF 1 specifically induces the expression of a FABP in 3T3 L 1 preadipocytes whereas the effect of insulin is likely via insulin ' s binding to the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor alpha subunit ( Mr 125 , 000 ) binds IGF 1 with a KD of 1 nM and IGF 2 with 10 times lower affinity . ^^^ Proliferation of neuronal precursor cells is stimulated by IGF 1 and IGF 2 via activation of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although regenerating liver cells continue to produce IGF 1 , we did not detect IGF 1 receptor mRNA during the first 24 h after hepatectomy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The biological activity of this variant is comparable in the patient ' s and normal fibroblasts , suggesting that the resistance to IGF 1 action can not be attributed to a defective IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that IGF 1 produced a specific stimulation of tyrosine kinase activity of the 97 kDa beta subunit of the IGF 1 receptor , resulting in autophosphorylation of the receptor and an increase in kinase activity toward a synthetic peptide substrate . ^^^ IGF 2 did not stimulate tyrosine phosphorylation of its own receptor , but was 25 % as active as IGF 1 in stimulating phosphorylation of the IGF 1 receptor . ^^^ Insulin also produced a delayed stimulation of IGF 1 receptor phosphorylation , but was unable to stimulate biological effects in these cells . ^^^ These data indicate that the IGF 1 receptor can be activated upon binding of IGF 1 , and to a lesser extent IGF 2 , in intact cells to mediate cellular events . ^^^ The nature of the signal generated by the IGF 1 receptor appears to vary depending on the ligand that occupies it . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report two chicken sequences that , by comparison with known tyrosine kinases , appear to correspond to the tyrosine kinase domain of the insulin receptor homologue ( CTK 1 ) and the IGF 1 receptor homologue ( CTK 2 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In combination with PdBu , however , IGF 1 or insulin , at concentrations sufficient to act through the IGF 1 receptor , were highly synergistic . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The Mr of pp 87 was identical to that of the insulin and IGF 1 receptor beta subunits . ^^^ The time course and dose dependence of pp 70 phosphorylation in response to hormone paralleled that of insulin and IGF 1 receptor autophosphorylation . ^^^ These results demonstrate that both insulin and IGF 1 receptors are active tyrosine kinases in fetal neurons , and that pp 70 represents a potential endogenous substrate for the insulin and IGF 1 receptor kinases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Xenopus oocytes carry IGF 1 receptors , and undergo meiotic maturation in response to binding of IGF 1 or insulin to the IGF 1 receptor . ^^^ Maturation is initiated upon activation of the IGF 1 receptor tyrosine kinase and requires tyrosine dephosphorylation of p34cdc2 , the kinase component of maturation promoting factor ( MPF ) . ^^^ In cell free systems , antibodies to phosphotyrosine recognized the oocyte IGF 1 receptor and modulated its ligand induced tyrosine kinase activity in a biphasic manner , with a stimulation at 40 micrograms / ml and an inhibition at higher concentrations . ^^^ Taken together , these results point to at least two levels of anti phosphotyrosine antibody action : ( 1 ) the IGF 1 receptor signalling system , and ( 2 ) a regulatory step of MPF activation , which might be distinct of the well documented inactivating phosphorylation of p34cdc2 . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Preincubation with 4 nM IGF 1 resulted in a 50 60 % decrease in IGF 1 receptor binding , accompanied by marked decreases in IGF 1 stimulated [ 3H ] aminoisobutyric acid uptake ( 50 60 % ) and [ 3H ] thymidine incorporation ( 80 90 % ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The high concentration ( 0 . 2 1 . 0 microgram / ml ) of insulin required for cell growth can be replaced by a low concentration of IGF 1 ( 10 20 ng / ml ) , indicating that insulin probably acts through a low affinity interaction with the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 induced change in IGFBP levels was not a type 1 IGF receptor mediated effect on IGFBP synthesis because ( a ) high concentrations of insulin did not mimic IGF 1 ' s effect ; ( b ) IGF 2 and IGF 1 analogues having reduced affinity for the IGF 1 receptor were equipotent with IGF 1 in increasing medium IGFBPs ; ( c ) [ QAYL ] IGF 1 , and IGF 1 analogue having normal receptor affinity and decreased affinity for IGFBPs , had no effect ; and ( d ) alpha IR 3 , a monoclonal antibody specific for the type 1 IGF receptor , did not block IGF 1 stimulated increases in IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These data , and the lack of linear growth in response to exogenous GH therapy in one patient , suggest a GH resistant state , either secondary to impaired bioactivity of IGF 1 , or a defect at or distal to the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The increase in [ 125I ] IGF 1 binding to bovine fibroblast monolayers was primarily due to association of hIGFBP 3E . coli with the cell surface ; there was no significant change in IGF 1 receptor number or affinity under these conditions . ^^^ Cell associated IGFBP 3E . coli ( 72 h preincubation conditions ) had a 10 fold lower affinity for IGF 1 compared to hIGFBP 3E . coli in solution and a 2 fold lower affinity compared to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , the IGF 1 receptor appears to function as an IGF 1 activated protein tyrosine kinase in chromaffin cells . ^^^ The tyrosine kinase activity of the IGF 1 receptor presumably mediates the effects of IGF 1 on chromaffin cell function . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mechanisms responsible for the transient increment in IGF 1 receptor number were not assessed , although it is likely that the decline in IGF 1 receptor content after 72 hours in differentiation medium was a consequence of down regulation by the IGF 2 that accumulated in the medium ( 35 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 2 binds to two receptors on the surface of many cell types : the IGF 1 receptor and the mannose 6 phosphate ( Man 6 P ) / IGF 2 receptor . ^^^ There is consensus that the cellular effects of IGF 2 are mediated by the IGF 1 receptor via activation of its intrinsic tyrosine kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our findings indicate that interaction of insulin with its own receptor , and not with IGF 1 receptor , triggers the proliferation of LB cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It thus appears that IGF 1 and IGF 2 are mitogens for normal and transformed human keratinocytes and that their actions are primarily mediated through the type 1 IGF receptor , whereas insulin is a mitogen through both the IGF 1 receptor and the insulin receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine the structural requirements for IGF 1 activated kinase activity , we have examined the effect of dissociation of the two alpha beta dimers of the IGF 1 receptor on beta subunit autophosphorylation . ^^^ The alpha beta dimers formed after treatment with 2 mM dithiothreitol ( DTT ) at pH 8 . 75 for 5 min were separated from IGF 1 receptor remaining as tetramers after DTT treatment by fast protein liquid chromatography on a Superose 6 gel filtration column . ^^^ Purification of the alpha beta dimers was confirmed by Western blot analysis using 125I labeled alpha IR 3 , a monoclonal antibody to the IGF 1 receptor . ^^^ Autophosphorylation of the IGF 1 receptor ( alpha beta ) 2 tetramer , treated without DTT or remaining after DTT treatment , is stimulated 1 . 6 2 . 9 fold by IGF 1 . ^^^ Both IGF 1 receptor dimers and tetramers exhibit similar kinase activities using the synthetic substrate Arg Arg Leu Ile Glu Asp Ala Glu Tyr Ala Ala Arg Gly , indicating that the failure to detect autophosphorylation of the IGF 1 receptor dimers does not result from inactivation of the kinase by DTT treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since the inhibitory action of insulin is duplicated by 100 fold lower concentrations of insulin like growth factor 1 ( IGF 1 ) , inhibition appears to be mediated by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A mAb directed against the human IGF 1 receptor blocked the enhanced secretion of O 2 by human PMN that was caused by IGF 1 , but not GH , indicating that neutrophil priming induced by GH was not mediated by inducing extracellular release of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Oocyte receptors were composed of alpha subunits of approximately 130 kDa and a doublet of beta subunits of 95 and 105 kDa , which both had ligand induced phosphorylation patterns compatible with IGF 1 receptor beta subunits . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor in BPH prostate tissue of untreated patients was mainly localized in the basal layer of the epithelium , as demonstrated by immunohistochemical staining , whereas in the tissue from treated patients positive staining was found also in the glandular epithelium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 or high dose insulin transmodulates keratinocyte EGF receptor expression via the IGF 1 receptor in a dose and time dependent manner , increasing EGF receptor binding an average of 1 . 8 times up to a maximum of fourfold without altering EGF binding affinity . ^^^ Staining of normal human epidermis with an IGF 1 receptor specific monoclonal antibody demonstrates that IGF 1 receptors localize to the basal proliferative cell compartment , suggesting that IGF 1 receptor and EGF receptor pathway interactions may play a role in the regulation of epidermal growth and in the pathogenesis of hyperproliferative skin diseases . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To explore autocrine / paracrine action of IGFs in muscle , we studied the regulation of the IGF 1 receptor and the expression of IGF peptides during differentiation of the mouse BC3H 1 muscle cell line . ^^^ Differentiation from myoblasts to myocytes was associated with a 60 % decrease in IGF 1 receptor sites determined by Scatchard analysis . ^^^ Analysis of mRNA abundance and protein labeling studies indicated that the decrease in IGF 1 receptor sites was associated with similar reductions in IGF 1 receptor gene expression and receptor biosynthesis . ^^^ IGF 2 peptide gene expression was detected in myoblasts and increased 15 fold with differentiation ; the increase in IGF 2 gene expression preceded the decrease in IGF 1 receptor gene expression . ^^^ To explore the potential role of endogenous IGF 2 in the differentiation associated decrease in IGF 1 receptor expression , we investigated the effects of IGF 2 treatment in myoblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor number for breast muscle although not statistically significant ( p greater than . 05 ) , indicated a trend towards differences between the slow growing Leghorn strain and the faster growing Cornish strain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
With these same in vitro methodologies , there was normal T lymphocyte line responsiveness to insulinlike growth factor 1 ( IGF 1 ) or insulin concentrations greater than 8 . 6 pM ; both of these responses could be completely blocked by preincubation with an antibody to the IGF 1 receptor . ^^^ These findings suggest that , despite resistance to physiological levels of insulin , the high circulating insulin concentrations present in the serum of these patients could mediate unwanted tissue specific growth through an intact IGF 1 receptor effector mechanism . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the total number of binding sites and IGF 1 receptor mRNA levels were 148 % and 240 % higher in astrocytes from 21 day old compared with 1 day old brains . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although normal AM did not have specific 125I labeled recombinant IGF 1 binding , AM activated by chrysotile asbestos or lipopolysaccharide in vitro or from individuals with ILD had detectable binding that could be inhibited by an anti IGF 1 receptor monoclonal antibody in a dose dependent fashion . ^^^ Autoradiography with 125I labeled recombinant IGF 1 revealed binding to the IGF 1 receptor on the surface of activated AM , and the percentage of labeled cells was reduced with anti IGF 1 receptor monoclonal antibody or excess unlabeled recombinant IGF 1 . ^^^ Hybridization of total AM RNA to a 32P labeled IGF 1 receptor riboprobe using solution hybridization demonstrated IGF 1 receptor mRNA transcripts in AM from an individual with asbestosis , consistent with active expression of the IGF 1 receptor gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Two color flow cytometric analysis of mononuclear cells stained with mouse monoclonal antibodies specific for the human IGF 1 receptor , the human insulin receptor , and monoclonal antibodies directed against specific monocyte and lymphocyte subset cell surface antigens revealed that both IGF 1 receptors and insulin receptors were present on nearly all monocytes and B lymphocytes , but were present on only 2 % of T lymphocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because of the sequence homology and tertiary structure similarities between proinsulin ( PI ) and insulin like growth factor 1 ( IGF 1 ) , it is possible that PI interacts with the IGF 1 receptor with higher affinity than insulin . ^^^ We conclude that in human liver , muscle , and adipose tissue , PI does not interact with the IGF 1 receptor at a higher affinity than insulin , and the affinity of IGF 1 receptors is several fold lower than that of insulin receptors . ^^^ It is , therefore , unlikely that if PI were to be administered to man any of its biological effects would be by interacting with the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Consistent with these findings , IGF 1 activates hexose uptake by Xenopus oocytes with a KA ( 3 nM ) identical with its KD , while IGF 2 and insulin activate hexose uptake with KA values of 50 nM and 200 250 nM , respectively , suggesting activation mediated through an IGF 1 receptor . ^^^ The IGF 1 receptor kinase is implicated in signal transmission from the receptor , since anti tyrosine kinase domain antibody blocks IGF 1 stimulated kinase activity in vitro and , when microinjected into intact oocytes , prevents IGF 1 stimulated hexose uptake . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
At the time at which these transcripts were maximally expressed ( embryonic day 20 ) , the regional analysis indicated that IGF 1 receptor transcripts were widely distributed in the brain . ^^^ In contrast , insulin receptor transcripts were restricted to certain areas in which they were coexpressed with the IGF 1 receptor transcripts . ^^^ However , astrocytes expressed preferentially IGF 1 receptor transcripts , while young progenitors for oligodendrocytes expressed high levels of insulin receptor transcripts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding studies revealed that a construct comprising an IGF 1 receptor in which the 68 N terminal amino acids of the insulin receptor alpha subunit had replaced the equivalent IGF 1 receptor segment displayed a markedly increased affinity for insulin . ^^^ In contrast , the corresponding IGF 1 receptor sequence is not critical for high affinity IGF 1 binding . ^^^ We have previously shown that exchanging exons 1 , 2 , and 3 of the insulin receptor with the corresponding IGF 1 receptor sequence results in loss of high affinity for insulin and gain of high affinity for IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Its effects in stimulating gonadotropin release were suppressed by administration of anti IGF 1 receptor antibody ( 1 mg / l ) . ^^^ These data suggest that IGF 1 enhances pituitary gonadotropin release via the IGF 1 receptor , but its effect on the hypothalamus was not confirmed . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using blocking anti receptor antibodies , it could be shown that the differentiation induced by these factors , in combination with PMA , was primarily mediated through the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to identify a possible interaction between androgens and these growth regulating factors , we investigated the effect of testicular suppression induced androgen withdrawal on both EGF and IGF 1 receptor concentrations in prostatic tissue from patients affected by BPH treated with a long acting luteinizing hormone releasing hormone analog . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The greater effects of IGF 1 compared with the effect of insulin are compatible with both effects being mediated through the IGF 1 compared with the effect of insulin are compatible with both effects being mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In BALB / c 3T3 cells pretreated with platelet derived growth factor ( PDGF ) and epidermal growth factor ( EGF ) ( primed competent cells ) , insulin like growth factors 1 and 2 ( IGF 1 and IGF 2 ) bind to their own receptors ( IGF IR and IGF IIR ) and stimulate calcium influx and DNA synthesis by a mechanism involving a 40 kDa pertussis toxin substrate . ^^^ Therefore , the IGF 1 signaling pathway may also be uncoupled between the IGF IR and Gi 2 alpha in quiescent cells and restored by PDGF and EGF . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , the p SMC and HV SMC expressed similar levels of message for the genes N myc , L myc , Ha ras , fos , sis , myb , LDL receptor , EGF receptor , IGF 1 receptor , IGF 2 , and HMG CoA reductase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Scatchard analyses and Northern blot hybridization revealed that both the EGF / TGF alpha receptor and the IGF 1 receptor were overexpressed in CE48T / VGH cells . ^^^ Furthermore , ligand dependent autophosphorylation of the EGF receptor and the IGF 1 receptor was clearly detected using antireceptor and antiphosphotyrosine antibodies . ^^^ Autocrine regulation was strongly indicated by the following evidence : ( a ) CE48T / VGH cells were found to express TGF alpha and IGF 1 genes , ( b ) serum free conditioned medium promoted the growth of CE48T / VGH cells and stimulated the autophosphorylation of the EGF / TGF alpha receptor and the IGF 1 receptor , and ( c ) the addition of IGF 1 receptor antibodies significantly suppressed CE48T / VGH cell growth under serum free conditions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In cell free systems , vanadate caused a 12 fold stimulation of autophosphorylation of the oocyte IGF 1 receptor in the absence , but not in the presence , of IGF 1 and inhibited largely , but not totally , receptor dephosphorylation induced by an extract of oocytes rich in phosphotyrosyl phosphatase activities . ^^^ These effects might result from a direct or indirect action of vanadate on the IGF 1 receptor kinase and on MPF activity . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The reduced affinity and biologic activity may result from several things : the presence of the unprocessed IGF 1 moiety , the large size of the IgG 3 IGF1 chimeric protein ( 160 kDa ) compared with IGF 1 ( 7 kDa ) , and three amino acid substitutions in rat IGF 1 compared with human IGF 1 , which may lead to decreased affinity for the human IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The relative affinities of IGF 1 and IGF 2 for the primary IGF 1 receptor correlate with their anabolic activities in bone cultures and suggest that the IGF 1 receptor mediates the growth promoting effects of both agents in bone . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A blocking antibody against the IGF 1 receptor ( alpha IR 3 ) significantly reduces IGF 1 stimulated proliferation in a dose dependent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Under reducing conditions , the labeling of proteins with Mr of 130 , 000 and 260 , 000 , corresponding to the alpha subunit of IGF 1 receptor and its dimer , respectively , was observed . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To assess the stability of the photoaffinity labeled IGF 1 receptor complex , quiescent monolayers of MG 63 cells were incubated with ANBz 125I IGF 1 at 2 C , photolyzed , and then warmed to 37 C . ^^^ Under these conditions the photoaffinity labeled IGF 1 receptor complex was relatively stable , with a half life of 11 + / 2 h in five experiments . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that Man 6 P containing proteins and IGF 2 act as mitogens in developing brain by interaction with the Man 6 P / IGF 2 receptor and the IGF 1 receptor , respectively . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 ( 5 50 nM ) had little effect on GPI hydrolysis in these cells as well as in CHO cells expressing the human IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The presence of insulin and IGF 1 receptor binding site subtypes is not correlated with structurally different receptor binding subunits since only a single population of binding subunits is observed ( apparent molecular weight of 125 + / 2 . 7 kD ) in embryonic and adult sclera . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that the beta subunit of the IGF 1 receptor comigrated on polyacrylamide gels with a component of the 95 kDa glycoprotein region from src transformed cells under both reducing and nonreducing gel conditions and had a very similar partial phosphopeptide map . ^^^ To further test the hypothesis that the beta subunit of the IGF 1 receptor becomes tyrosine phosphorylated in cells transformed by pp60src , a human cell line that expressed the IGF 1 receptor was transformed by src . ^^^ Comparison of IGF 1 receptors immunoprecipitated from normal and transformed cells revealed that the beta subunit of the IGF 1 receptor became constitutively tyrosine phosphorylated in src transformed cells . ^^^ Moreover , IGF 1 receptor phosphorylation induced by src was synergistic with that induced by the hormone : IGF 1 stimulated autophosphorylation of the receptor was much greater in src transformed cells than in untransformed HOS cells even at maximal concentrations of IGF 1 . ^^^ Our data demonstrate that the IGF 1 receptor becomes constitutively tyrosine phosphorylated in src transformed cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When autophosphorylation of the IGF 1 receptor was determined in [ 32P ] labelled cells , IGF 1 increased radioactivity in a 100 K Da phosphoprotein , presumably beta subunit of the IGF 1 receptor , both in quiescent and in primed competent cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have isolated genomic clones that contain the promoter region of the rat IGF 1 receptor gene . ^^^ The rat IGF 1 receptor gene promoter region appears to have some sequences similar to both `` housekeeping ' ' and highly regulated promoters and may be an example of an intermediary class of regulatory region . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cross linking of [ 125I ] IGF 1 demonstrated that glioma tissue expressed the same lower mol wt ( approximately 118 kDa ) alpha subunit as the normal brain confirming the neural origin of the cells expressing the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Specificity of the 125I IGF 1 binding sites was confirmed by analogue specificity studies and in experiments utilizing monoclonal antibody to the IGF 1 receptor , alpha IR 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The presence of high affinity , specific IGF 1 receptor binding in rabbit arteries suggests that IGF 1 plays an important role in regulating the multiplication of arterial smooth muscle cells ; a role that may prove important in different pathologic processes . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Based on the observation that insulinlike growth factor 1 ( IGF 1 ) can stimulate glucose utilization in nondiabetic subjects and that the action of the IGF 1 receptor is normal in the skeletal muscle of patients with non insulin dependent diabetes mellitus ( NIDDM ) , it seems possible that IGF 1 might provide an effective acute treatment for the hyperglycemia of NIDDM . ^^^ There was no change in IGF 1 binding in muscle from obese or diabetic subjects , and the structural characteristics of the IGF 1 receptor were not altered , as determined by electrophoretic mobility . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor alpha subunits ( Mr approximately 130 , 000 ) bound IGF 1 and IGF 2 with identical affinity ( Kd approximately 1 nM ) and insulin with about 1000 times lower affinity . ^^^ IGF 1 and IGF 2 stimulated tyrosine kinase activity and autophosphorylation of the IGF 1 receptor beta subunit ( Mr approximately 94 , 000 ) with equal potency ( ED 50 approximately 1 nM ) , whereas insulin was approximately 5 times less potent . ^^^ It is concluded that IGF 1 and IGF 2 can exert their biological effects in chromaffin cells by activation of the IGF 1 receptor tyrosine kinase or by interaction with the IGF 2 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , the alpha IR 3 antibody , which competes for IGFI binding , was found to interact with the same 52 amino acids of the IGFIR which determines hormone specificity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present studies , we show that a monoclonal antibody to the IGF 1 receptor , alpha IR 3 , inhibits the binding of IGF 1 but not IGF 2 to the expressed receptor in intact cells and after solubilization . ^^^ Moreover , this antibody inhibits the ability of both IGF 1 and 2 to stimulate the kinase activity of the IGF 1 receptor in intact cells . ^^^ These results indicate that alpha IR 3 binds to the IGF 1 receptor in such a way that it does not inhibit the binding of IGF 2 but does inhibit the subsequent ability of the receptor to be activated to transmit a signal . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By studying IGF 2 ' s growth promoting activity in these cells in a wide range of concentrations , we show that IGF 2 triggers its mitogenic response via IGF II / M6P receptor at low concentrations , whereas it is mainly acting via IGF 1 receptor at high concentrations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To study the involvement of IGF 1 and the IGF 1 receptor in the development of nephropathy , one of the major complications of diabetes mellitus , we measured the expression of these genes in the kidney and in other tissues of the streptozocin induced diabetic rat . ^^^ We observed a 2 . 5 fold increase in the steady state level of IGF 1 receptor mRNA in the diabetic kidney , which was accompanied by a 2 . 3 fold increase in IGF 1 binding . ^^^ In addition to this increase in IGF 1 binding to the IGF 1 receptor , there was also binding to a lower molecular weight material that may represent an IGF binding protein . ^^^ Because the IGF 1 receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain , we hypothesize that , among other factors , high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody for the IGF 1 receptor inhibited both motility and glycolytic CO 2 production , indicating that both processes are receptor mediated . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to precisely define sites of IGF 1 mRNA synthesis , and their relationship to IGF 1 receptor sites , we have applied the techniques of in situ hybridization and in vitro receptor autoradiography in rat brain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 is slightly more potent , paralleling its higher affinity for the IGF 1 receptor . ^^^ Antibody blockade of the IGF 1 receptor inhibits growth stimulation induced by both IGFs , suggesting that this receptor mediates the growth effects of both peptides . ^^^ However , IGF 1 receptor blockade does not inhibit estrogen ( E 2 ) induced growth suggesting that secreted IGFs are not the major mediators of E 2 action . ^^^ Blockade of the IGF 1 receptor inhibits anchorage independent and monolayer growth in serum of a panel of breast cancer cell lines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Measurements of explant radioactivity were performed in order to evaluate IGF 1 uptake and release as a function of time , medium concentration and patient , in tumors with low IGF 1 receptor levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To examine the role of the N terminal part of the insulin like growth factor 1 ( IGF 1 ) receptor and insulin receptor in determining ligand specificity , we prepared an expression vector encoding a hybrid receptor where exon 1 ( encoding the signal peptide and seven amino acids of the alpha subunit ) , exon 2 , and exon 3 of the insulin receptor were replaced with the corresponding IGF 1 receptor cDNA ( 938 nucleotides ) . ^^^ To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF 1 receptor and the insulin receptor , all three receptors were expressed in baby hamster kidney ( BHK ) cells as soluble molecules and partially purified before characterization . ^^^ The hybrid IGF I / insulin receptor bound IGF 1 with an affinity comparable to that of the wild type IGF 1 receptor . ^^^ These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF 1 receptor and , furthermore , that the binding specificity for IGF 1 is encoded within the nucleotide sequence from 135 to 938 of the IGF 1 receptor cDNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , antibodies to other cytoplasmic regions did not recognize the IGF 1 receptor as well as the insulin receptor . ^^^ In addition , these results suggest that a portion of the insulin receptor is highly homologous to that of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Evidence that receptor aggregation may play a role in transmembrane signaling through the insulin like growth factor 1 receptor . alpha IR 3 is a mouse monoclonal antibody that binds to an epitope on the human insulin like growth factor 1 ( IGF 1 ) receptor and inhibits [ 125I ] IGF 1 binding to this receptor on human skin fibroblasts ( HSF ) and Hep G 2 human hepatoblastoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity labeling of the 130 kDa protein , presumably the alpha subunit of the IGF 1 receptor , was blocked by excess amount of unlabeled IGF 1 . ^^^ These results suggest that relatively low concentrations of IGF 1 stimulate calcium influx in primed competent BALB / c 3T3 cells by activating a calcium permeable cation channel via the IGF 1 receptor and that calcium influx may be a critical intracellular message of the progression activity of IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , the mitogenic effects of insulin ( at concentrations where it activates the IGF 1 receptor ) or of IGF 1 neither were notably influenced by cycloheximide pretreatment nor were inhibited by IBMX ( in the presence of IBMX , the onset of S phase was delayed by several hours ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and insulinlike growth factor 1 ( IGF 1 ) receptors during central nervous system development : expression of two immunologically distinct IGF 1 receptor beta subunits . ^^^ Two dimensional tryptic phosphopeptide analysis showed that the 92 and 97 kDa subunits of the IGF 1 receptor are related but distinct proteins . ^^^ Thus , two distinct beta subunits may be present in a single IGF 1 receptor in brain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
For this purpose we characterized rat IGF 1 receptor cDNAs that were cloned from a simian virus 40 transformed rat granulosa cell cDNA library . ^^^ IGF 1 receptor gene expression was studied during the perinatal period and at various intervals until early adulthood . ^^^ Overall , steady state IGF 1 receptor mRNA levels decreased dramatically during postnatal development ; however , the extent of the decrease differed among the various tissues studied . ^^^ The molecular mechanisms underlying this apparent divergent transcriptional control of the IGF 1 and IGF 1 receptor genes warrant further study . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because IGF BPs are present in extracellular fluids and can modulate IGF 1 receptor interaction , induction of this protein may be an important mediator of IGF action . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Antibodies for six distinct epitopes reacted with a subfraction of IGF 1 receptors , as shown by inhibition of 125I IGF 1 binding , precipitation of 125I IGF 1 receptor complexes or immunodepletion of receptor from tissue extracts before binding assays . ^^^ After DTT treatment , the IGF 1 receptor was partially converted to a lower molecular mass form which was not immunoreactive . ^^^ It is concluded that the anti ( insulin receptor ) antibodies do not react directly with IGF 1 receptor polypeptide , and that the apparent immunoreactivity of a subfraction of IGF 1 receptors reflects their physical association with insulin receptors , both in cell extracts and in intact cells . ^^^ The most likely basis for this association appears to be a ' hybrid ' receptor containing one half ( alpha beta ) of insulin receptor polypeptide and the other ( alpha ' beta ' ) of IGF 1 receptor polypeptide within the native ( alpha beta beta ' alpha ' ) heterotetrameric structure . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , hybridization of a 32P labeled IGF 1 receptor probe to Northern blots of poly ( A+ ) RNA prepared from cells grown at 33 C and 40 C revealed an 11 kilobase rat IGF 1 receptor mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The possibility of a paracrine mitogenic activity of the fetal lung fibroblast produced IGF 1 in cultures was suggested by demonstrating a reduction in DNA synthesis in cultures incubated with either the IGF 1 monoclonal antibody or an IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that pp 175 is a common substrate for insulin and IGF 1 receptor kinases which , in FRTL 5 cells , is associated with the cytoskeleton . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Surprisingly , IGF 1 was not found to be more potent than insulin on a molar basis , which did not provide evidence for the exclusive involvement of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We previously demonstrated the presence of IGF 1 receptor and synthesis in glomerular mesangial cells . ^^^ Cross linking studies showed a single band of radioactivity with an estimated mol wt of 145K , consistent with the alpha subunit of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockade of the IGF 1 receptor of cytotrophoblasts with alpha IR 3 , a monoclonal anti IGF 1 receptor antibody , prevented the stimulation of 3 beta HSD activity by IGF 1 , but did not alter insulin ' s stimulatory effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor alpha subunits ( the IGF binding subunit ) migrated at : liver , 139 , 000 ; brain , 125 , 000 ; RPE , 125 , 000 and 135 , 000 ( two sizes ) ; and retina , 125 , 000 and 135 , 000 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The monoclonal antibody to the IGF 1 receptor ( alpha IR 3 ) inhibits 125I IGF 1 binding and immunoprecipitates the IGF 1 receptor . ^^^ In addition , the alpha subunit of IGF 1 receptor is approximately 10 , 000 Mr larger than the alpha subunit of insulin receptor , and IGF 1 stimulates phosphorylation of the beta subunit of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because IGF 1 binding to the fibroblasts from the patient was normal and alpha subunit of IGF 1 receptor was 135 KDa , the defect was specific to the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity labeling revealed that beta 2m enhanced IGF 1 receptor number , and Northern analysis and radioimmunoassay showed that beta 2m increased steady state IGF 1 transcripts and medium IGF 1 polypeptide levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Covalent crosslinking studies revealed that the human adrenal gland IGF 1 receptor binding subunit migrated on dodecyl sulfate polyacrylamide gels with Mr = 135 , 000 , which is identical to the migration of IGF 1 receptor binding subunits isolated from other tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , IGF 1 or Mn / MgATP , but not insulin , treatment of immunoaffinity purified alpha beta heterodimeric IGF 1 receptors induced the formation of an alpha 2 beta 2 heterotetrameric IGF 1 receptor complex . ^^^ Conversely , the IGF 1 receptor specific monoclonal antibody ( alpha IR 3 ) immunoprecipitated all the IGF 1 binding activity , but not insulin receptors . ^^^ The simultaneous treatment of pooled equal amounts of alpha beta heterodimeric insulin and IGF 1 receptors with a combination of insulin and IGF 1 resulted in the formation of alpha 2 beta 2 heterotetrameric insulin and IGF 1 receptor complexes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 2 ( IGF 2 ) : a potential autocrine / paracrine growth factor for human breast cancer acting via the IGF 1 receptor . ^^^ Affinity labeling studies revealed that IGF 2 could also compete for binding to the 130 , 000 mol wt alpha subunit of the IGF 1 receptor . ^^^ A monoclonal antibody to the IGF 1 receptor inhibited the mitogenic effects of IGF 2 in MCF 7L and MDA 231 cells , suggesting that this receptor mediates the growth effects of IGF 2 in these breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor alpha subunit ( MW 130 , 000 ) bind IGF 1 and IGF 2 with equal affinity ( Kd approximately 4 7 nM ) , and insulin with approximately 100 times lower affinity . ^^^ Tyrosine kinase activity and autophosphorylation of the IGF 1 receptor beta subunit ( MW 95 , 000 ) are stimulated by IGF 1 and IGF 2 with equal potency ( ED 50 approximately 0 . 5 nM ) . ^^^ Activation of thymocytes by concanavalin A increased the number of IGF 2 receptors 2 fold , whereas IGF 1 receptor binding and IGF stimulated amino acid transport were unaltered . ^^^ We conclude that the effect of IGF 1 and IGF 2 in thymocytes is mediated via binding to the IGF 1 receptor and stimulation of its tyrosine kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This increase in binding was associated with increased steady state levels of insulin receptor and IGF 1 receptor mRNA levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Comparison of receptor occupancy with stimulation of glucose uptake and GTmRNA expression suggests that insulin exerts its effects through the IGF 1 receptor . ^^^ These results demonstrate that the IGF 1 receptor mediates chronic regulation of transporter mRNA expression and protein synthesis and activity in cultured rat muscle cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The subunit sizes of the B 2 reactive IGF 1 receptor were similar to those of the insulin receptor . ^^^ The presence of two distinct binding and immunoreactive species of IGF 1 receptors in human placenta raises the possibility that cell or tissue specific isotypes of the IGF 1 receptor could mediate the different biological actions of IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Characterization of monoclonal antibodies to the IGF 1 receptor that inhibit IGF 1 binding to human cells . ^^^ A mouse monoclonal antibody directed against the human placental IGF 1 receptor is shown to completely inhibit IGF 1 binding to both human placental membranes and circulating human mononuclear leukocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The formation of the alpha 2 beta 2 heterotetrameric IGF 1 receptor complex from the partially purified alpha beta heterodimers was time dependent with half maximal formation in approximately 30 min at saturating IGF 1 concentrations . ^^^ In addition , IAN did not affect the Mn / MgATP dependent noncovalent association of IGF 1 receptor alpha beta heterodimers into an alpha 2 beta 2 heterotetrameric state . ^^^ These data indicate that IGF 1 induces the covalent association of isolated alpha beta heterodimeric IGF 1 receptor complexes into a disulfide linked alpha 2 beta 2 heterotetrameric state whereas Mn / MgATP induces a noncovalent association . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity labeling of receptors demonstrated that insulin and IGF 1 both bind to a 135 kDa protein that corresponds to the insulin and IGF 1 receptor alpha subunits . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These effects were blocked by the insulin receptor monoclonal antibody MA 10 , but not by the IGF 1 receptor antibody alpha IR 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The identities of the insulin and IGF 1 receptor beta subunits in the two immunoprecipitates were confirmed by binding affinity , by phosphopeptide mapping after trypsin digestion , and by the distinct patterns of expression of the two receptors during differentiation . ^^^ Similarly , stimulation of phosphorylation of the beta subunit of the IGF 1 receptor by IGF 1 correlated with IGF 1 receptor occupancy . ^^^ In contrast , insulin stimulated phosphorylation of the beta subunit of the IGF 1 receptor at hormone concentrations that were associated with significant occupancy of the insulin receptor but negligible IGF 1 receptor occupancy . ^^^ These findings indicate that the IGF 1 receptor can be a substrate for the hormone activated insulin receptor tyrosine kinase activity in intact L 6 skeletal muscle cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An MAb that specifically binds to the IGF 1 receptor ( but not to the insulin receptor ) mediates a dose dependent inhibition of cell growth in basal media as well as IGF 1 , IGF 2 , or insulin supplemented media . ^^^ The IGF 1 receptor thus appears to be the common pathway for the mitogenic activity by IGF 1 , IGF 2 , and insulin for human SCLC cell lines . ^^^ The demonstration of an IGF 1 precursor molecule , specific IGF 1 receptor binding , IGF 1 mediated growth stimulation , and inhibition of basal cell growth by an MAb to the IGF 1 receptor suggests that an IGF 1 like molecule can function in vitro as an autocrine growth factor for human SCLC cell lines . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It is suggested , therefore , that there exist in the FRTL 5 cell line at least two mechanisms for the regulation of growth , one activated at the level of the IGF 1 receptor and the other at the level of the TSH receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To identify structural characteristics of the closely related cell surface receptors for insulin and IGF 1 that define their distinct physiological roles , we determined the complete primary structure of the human IGF 1 receptor from cloned cDNA . ^^^ The 1337 residue , unmodified proreceptor polypeptide has a predicted Mr of 151 , 869 , which compares with the 180 , 000 Mr IGF 1 receptor precursor . ^^^ In analogy with the 152 , 784 Mr insulin receptor precursor , cleavage of the Arg Lys Arg Arg sequence at position 707 of the IGF 1 receptor precursor will generate alpha ( 80 , 423 Mr ) and beta ( 70 , 866 Mr ) subunits , which compare with approximately 135 , 000 Mr ( alpha ) and 90 , 000 Mr ( beta ) fully glycosylated subunits . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to gain insights into the substrate specificity of the structurally related insulin and IGF 1 receptor kinases , we have studied the action of highly purified receptors isolated from human placental membranes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the case of IGF 1 , alpha IR 3 potently inhibited AIB uptake at low hormone concentrations , but this inhibition was overcome by high hormone concentrations , consistent with impairment of IGF 1 action through the IGF 1 receptor . ^^^ In the case of insulin , the action of low concentrations ( i . e . 10 ng / ml ) was not inhibited , but that of higher insulin concentrations was , suggesting a dual receptor mechanism of cell stimulation by insulin . alpha IR 3 will be an important tool in further studies of the biology of the IGF 1 receptor in normal and abnormal human cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Monoclonal antibodies that preferentially recognize either the insulin receptor or the IGF 1 receptor were utilized to examine which receptors mediated the biological effects of these hormones . ^^^ The effects of insulin on both myoblasts and myotubes appeared to be mediated in part by the insulin receptor and in part by the IGF 1 receptor . ^^^ In myotubes , the effects of IGF 1 and 2 both appeared to be mediated through the IGF 1 receptor . ^^^ In myoblasts , the effects of the two IGFs appeared to be in part mediated by the IGF 1 receptor and in part mediated by either the IGF 2 receptor or another type of IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that these receptor preparations contained predominantly the IGF 1 receptor . ^^^ A monoclonal antibody that inhibits the insulin receptor kinase was found to inhibit the IGF 1 receptor kinase with the same potency with which it inhibits the insulin receptor . ^^^ In contrast , monoclonal antibodies to other parts of the insulin receptor only poorly recognized the IGF 1 receptor . ^^^ Thus , the IGF 1 receptor is structurally , antigenically , and functionally similar to but not identical with the insulin receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor was similar to the insulin receptor with respect to subunit structure ( beta alpha alpha beta ) , apparent sizes of deglycosylated alpha ( Mr = approximately 88 , 000 ) and beta ( Mr = approximately 67 , 000 ) subunits , and amino acid composition of the subunits . ^^^ Monoclonal antibody specific to each receptor recognized its own receptor whereas polyclonal anti human insulin receptor antibody cross reacted with the IGF 1 receptor , indicating that the receptors share one or more antigenic sites . ^^^ Further characterization of the purified IGF 1 receptor tyrosine protein kinase activity indicated that by analogy with the insulin receptor the monomeric alpha beta form of the IGF 1 receptor appears to have higher kinase activity than the intact receptor in the alpha 2 beta 2 form . ^^^ The IGF 1 receptor alpha subunit lacks residues corresponding to the N terminal 4 amino acids of the insulin receptor alpha subunit . ^^^ These results provide the first direct proof that the IGF 1 receptor is a molecule distinct from the insulin receptor despite numerous similarities . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , the brain IGF 1 receptor was not cleaved by neuraminidase , whereas , the placental IGF 1 receptor had increased mobility on SDS gels following neuraminidase treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The former represents a neuronal type of the IGF 1 receptor alpha subunit , whereas the latter probably represents an alpha dimer . ^^^ In contrast , the binding moiety in cultured glial cells was of Mr = 135 , 000 , which was identical to the IGF 1 receptor alpha subunit of placenta . ^^^ Thus mature brain , despite its cellular heterogeneity , expresses a structural subtype of IGF 1 receptor which appears to be unique to differentiated neurons . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Apparent molecular mass of the alpha subunits of the IGF 1 receptor was 125 kDa in neuronal and 135 kDa in glial cells . ^^^ IGF 1 induced autophosphorylation of the IGF 1 receptor beta subunit in lectin purified membrane preparations in a dose dependent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study demonstrates that transducin also serves as in vitro substrate for an endogenous IGF 1 receptor kinase isolated from ROS membranes . ^^^ The previously reported presence of IGF 1 in the vitreous , together with our present studies , strongly suggest that the IGF 1 receptor kinase , through phosphorylation of endogenous proteins like transducin , could play a role in mediating transmembrane signal transduction in ROS . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Skeletal muscle has receptors with relative specificity for insulin and IGF 1 respectively ; L 6 cells also have two classes of receptors , one is kinetically similar to the IGF 1 receptor from skeletal muscle ; the other , which binds insulin with relatively high affinity has even greater affinity for IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor beta subunit is represented by two phosphoproteins of molecular mass 95 and 105 kDa . ^^^ The finding of pp 185 in these neural related cells as well as in non neural tissues suggests that it may represent a ubiquitous endogenous substrate for both the insulin and IGF 1 receptor kinases . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have separated these sites and purified the high affinity IGF 1 receptor 1 , 300 fold , with an overall yield of 9 . 9 % , using wheat germ agglutinin Sepharose chromatography , insulin affinity chromatography , and IGF 1 affinity chromatography . ^^^ The high affinity IGF 1 receptor is composed of alpha and beta subunits with apparent molecular weights of 135 , 500 and 96 , 200 , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor in human testis : an immunohistochemical study . ^^^ The major positivity for the IGF 1 receptor was found in secondary spermatocytes and early spermatids , whereas Sertoli cells were less positive . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor was characterized on intact cells . ^^^ The Kd of the IGF 1 receptor was 1 . 47 10 10 ( 9 ) M , and the estimated number of sites was 64 , 000 receptors / cell . ^^^ The half maximal response to IGF 1 stimulation occurred at 1 . 3 10 10 ( 10 ) M , and a similar increase with insulin was observed at concentrations in the range of 10 ( 7 ) M , suggesting that this insulin action was mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor binds insulin with a 70 fold lower affinity than IGF 1 , and 30 70 fold higher levels of insulin are required to duplicate the effects of an optimal amount of IGF 1 . ^^^ In undifferentiated cells the IGF 1 receptor concentration is twice that of the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cross linking studies showed that 125I IGF 1 bound to a protein that had an Mr of approximately 125 , 000 , similar to the Mr of the alpha subunit of the IGF 1 receptor in other tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The binding characteristics and the size of the binding unit were found to be similar to those of the IGF 1 receptor found in cultured vascular smooth muscle cells . ^^^ Furthermore , insulin at high concentrations was found to interact with the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Triton 10 100 solubilization of the alkaline pH and DTT pretreated placenta membranes , followed by Bio Gel A 1 . 5m gel filtration chromatography , was found to effectively separate the alpha 2 beta 2 heterotetrameric and alpha beta heterodimeric IGF 1 receptor species , 125I IGF 1 binding to both the isolated alpha 2 beta 2 heterotetrameric and alpha beta heterodimeric complexes demonstrated a marked straightening of the Scatchard plots , compared to the placenta membrane bound IGF 1 receptors , with a 2 fold increase in the high affinity binding component . ^^^ Similar to the membrane bound IGF 1 receptor species , the 125I IGF 1 binding properties between the alpha 2 beta 2 heterotetrameric and alpha beta heterodimeric complexes were not significantly different . ^^^ IGF 1 stimulation of IGF 1 receptor autophosphorylation indicated that the ligand dependent activation of alpha beta heterodimeric protein kinase activity occurred concomitant with the reassociation into a covalent alpha 2 beta 2 heterotetrameric state . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using appropriate antibodies we were able to demonstrate that the IGF 1 receptor beta subunit has two subtypes of 95 kDa and 105 kDa . ^^^ Enzymatic digestion of IGF 1 receptor beta subunit subtypes by glycopeptidase F resulted in similar molecular masses ( 84 kDa and 86 kDa ) on SDS PAGE , which suggests that the difference in molecular masses between two subtypes is attributable to the differences in N linked complex type carbohydrate chains on the extracellular domain of beta subunits . ^^^ Analysis of IGF 1 receptor beta subunit subtypes in these cells may provide insights into the mechanism of action of IGF 1 on neural tissues . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The integrity of the IGF 1 receptor preparation in the two fiber types was identical as determined by affinity cross linking . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Covalent cross linking studies with [ 125I ] IGF 1 revealed an IGF 1 receptor alpha subunit with Mr congruent to 135 , 000 on dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions , as well as a smaller radiolabeled peptide , Mr = 116 , 000 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Competition studies with insulin , IGF 2 , and an anti IGF 1 receptor antibody are consistent with the presence of specific IGF 1 receptors , and SDS PAGE showed binding to a 130 kDa subunit identical to that of receptors from human placenta . ^^^ In addition , we show that IGF 1 is more potent than estradiol and comparable to EGF in stimulating in vitro proliferation of MCF 7 cells , and that IGF 1 stimulated proliferation of these cells is inhibited by a blocking monoclonal antibody against the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cultured , transformed T lymphocytes from an infant with leprechaunism fail to augment basal colony formation in response to physiologic insulin concentrations in vitro ( compared to a doubling seen in normal subjects ) , but respond normally to supraphysiologic insulin concentrations , the effect of which is competitively inhibited by a monoclonal antibody to the IGF 1 receptor . ^^^ Thus , insulin action mediated through the IGF 1 receptor may initiate growth promoting tissue effects in the face of limited insulin effect on glucose metabolism . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody specific for the human IGF 1 receptor inhibited IGF 1 binding to the expressed receptor and immunoprecipitated polypeptides of apparent Mr values approximately 135 , 000 and 95 , 000 from metabolically labeled lysates of the transfected cells but not control cells . ^^^ The human IGF 1 receptor expressed in these cells was capable of IGF 1 stimulated autophosphorylation and phosphorylation of endogenous substrates in the intact cell . ^^^ These results indicate that the isolated cDNA encodes a functional IGF 1 receptor and that there are no inherent differences in the abilities of the insulin and IGF 1 receptors to mediate rapid and long term biological responses when expressed in the same cell type . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Two types of IGF receptor are present in PC 12 cells and the dose response curves suggest that the mitogenic responses to IGF ' s are mediated by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Data from crosslinking experiments with and without neuraminidase treatment indicate that the binding subunits of the retinal IGF 1 receptor exist in two subpopulations ( Mr = 121 and 131 kDa ) , and that the larger of the two subunits has either a greater number or more exposed sialic acid residues . ^^^ In these characteristics , the retinal IGF 1 receptor is similar to the retinal insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that 1 ) the defect is specific to the insulin receptor binding in these patients , 2 ) insulin and IGF 1 activate glucose incorporation and alpha aminoisobutyric acid uptake mainly through their own specific receptors , but 3 ) the IGF 1 receptor appears to have a more important role in stimulating thymidine incorporation than the insulin receptor in physiological condition or , alternatively , an unknown postreceptor process with cascade signal transmission may overcome the decreased insulin receptor binding to produce a normal dose response curve . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have recently identified high and low affinity insulin like growth factor 1 ( IGF 1 ) binding sites in solubilized human placental membranes and purified the high affinity IGF 1 receptor by IGF 1 affinity chromatography ( Tollefsen , S . ^^^ To define the structural basis for high affinity IGF 1 binding , we have examined the effect of disulfide bond reduction on the binding parameters of the high affinity IGF 1 receptor . ^^^ We find that the disulfide bonds linking the two alpha beta dimers of the IGF 1 receptor heterotetramer are reduced by incubation at pH 8 . 75 with 2 mM dithiothreitol ( DTT ) for 5 min at room temperature . ^^^ Scatchard plots of IGF 1 binding to the IGF 1 receptor incubated at pH 8 . 75 with or without DTT indicate that the IGF 1 receptor alpha beta dimers have a 6 . 1 + / 1 . 6 ( mean + / S . ^^^ The total binding capacity of the IGF 1 receptor treated with DTT is 1 . 6 + / 0 . 3 ( mean + / S . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When IGF 1 receptor complexes were preincubated with unlabeled ATP for 10 min before addition of substrate , however , IGF 1 dependent 32P incorporation was observed within 2 min after addition of poly ( Glu , Tyr ) , 4 : 1 , and increased linearly for 20 min . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results demonstrate that [ 125I ] IGF 1 binding to erythrocytes can be used for clinical measurement of the IGF 1 receptor . . ^^^ Characterization of insulin like growth factor 1 receptor on human erythrocytes . [ 125I ] Insulin like growth factor 1 ( IGF 1 ) specifically bound to erythrocytes ; the binding was saturable , and time and temperature dependent . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Time , temperature , and pH dependence of peptide binding were characterized for the T cell IGF 1 receptor and the B cell insulin receptor and were consistent with previously described models for these receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Monoclonal antibody to the type 1 insulin like growth factor ( IGF 1 ) receptor blocks IGF 1 receptor mediated DNA synthesis : clarification of the mitogenic mechanisms of IGF 1 and insulin in human skin fibroblasts . ^^^ The mouse anti human IGF 1 receptor antibody alpha IR 3 binds with specificity to IGF 1 but not to insulin receptors in human placental membranes ; it also specifically inhibits the binding of 125I labeled IGF 1 but not 125I labeled insulin to suspensions of human skin fibroblasts in a dose dependent manner . alpha IR 3 competitively inhibits IGF 1 mediated stimulation of [ 3H ] thymidine incorporation into DNA . ^^^ However , the incremental effects of higher concentrations ( greater than 1 microgram / ml ) of insulin on [ 3H ] thymidine incorporation are inhibited by alpha IR 3 . alpha IR 3 is a highly specific antagonist of IGF 1 receptor mediated mitogenesis in human skin fibroblasts . ^^^ By using this antibody , it is shown directly that insulin can act through the IGF 1 receptor to stimulate DNA synthesis but can also activate this effect through the insulin receptor itself . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and IGF 1 dose responses for phosphorylation of the immunodepleted brain preparations suggested that the remaining tyrosine kinase activity was IGF 1 receptor mediated . ^^^ Thus , functional IGF 1 receptors are present in rat brain , and the doses of insulin typically used to evaluate insulin receptor tyrosine kinase activity will stimulate IGF 1 receptor tyrosine kinase activity as well . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody to the IGF 1 receptor ( alpha IR 3 ) inhibited IGF 1 binding by 50 % at a 1 : 1000 dilution and by 80 % at a 1 : 250 dilution . ^^^ IGF 1 receptor phosphorylation was studied in erythrocyte ghosts prepared by hypotonic lysis and solubilized in 1 % Triton . ^^^ This protein corresponds to the beta subunit of the IGF 1 receptor . ^^^ These data demonstrate that human erythrocytes have specific receptors for IGF 1 , and that this IGF 1 receptor , like the insulin receptor , undergoes ligand stimulated autophosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It is therefore not excluded that the IGF 1 receptor could be uncoupled by TPA , with persistent binding capacity for IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Unlabeled insulin competed poorly for the IGF 1 receptor , requiring 5000 ng / ml ( 667 nM ) to cause a 50 % reduction in binding , and did not compete at all for the IGF 2 receptor at concentrations up to 10 ( 5 ) ng / ml ( 17 . 8 microM ) . ^^^ The IGF 1 receptor was further characterized by reduced polyacrylamide gel electrophoresis of the disuccinimidyl suberate cross linked 125I labeled IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) 1 receptor was purified from Triton 10 100 solubilized human placental membranes by wheat germ agglutinin Sepharose chromatography followed by immunoaffinity chromatography using alpha IR 3 , a monoclonal antibody directed against the IGF 1 receptor . ^^^ It sedimented in glycerol gradients as a single species with a sedimentation coefficient of 13 . 7 S and gave three protein bands with Mr = approximately 300 , 000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis under nonreducing conditions , indicating that alpha 2 beta 2 is an intact form of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Adsorption specificity to this affinity matrix demonstrates that low coupling ratios of IGF 1 analog to agarose yield preparations that are highly selective in purifying IGF 1 receptor with minimal cross contamination by the insulin receptor present in the same placental extracts . ^^^ Incubation of the immobilized IGF 1 receptor preparation with [ gamma 32P ] ATP results in a marked phosphorylation of the receptor beta subunits , which appear as a doublet of Mr = 93 , 000 and 95 , 000 upon electrophoresis on dodecyl sulfate polyacrylamide gels . ^^^ The immobilized IGF 1 receptor preparation exhibits tyrosine kinase activity toward exogenous histone . ^^^ The characteristics of the IGF 1 receptor associated tyrosine kinase are remarkably similar to those of the insulin receptor kinase . ^^^ Thus , prior phosphorylation of the immobilized IGF 1 receptor preparation with increasing concentrations of unlabeled ATP followed by washing to remove the unreacted ATP results in a progressive activation of the receptor associated histone kinase activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody to the type 1 IGF 1 receptor ( alpha IR 3 ) prevented the inhibitory effects of IGF 1 on basal and GHRH stimulated GH secretion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These observations suggest that the thiol redox state of the IGF 1 receptor in vivo is an important determinant of receptor conformation and therefore of the biological responses to IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor is a tyrosine kinase capable of phosphorylating the receptor itself and other substrates . ^^^ A human polyclonal IgG ( pIgG ) , previously characterized as anti insulin receptor antibody , able to inhibit insulin receptor kinase activity , was used to further investigate subunit homologies and differences in antigenicity and functional regulation between IGF 1 and insulin receptors , IGF 1 receptor tyrosine kinase was stimulated by a IGF 1 analog ( aIGF 1 ) , produced by DNA recombinant technology , pIgG was able to inhibit IGF 1 receptor kinase activity , thus revealing antigenic homologies between the kinase domains of insulin and IGF 1 receptors . ^^^ However the more pronounced inhibition of IGF 1 receptor compared with insulin receptor kinase activity by pIgG suggests the existence of different regulatory mechanisms . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These observations indicate that MC express predominantly receptors for IGF 1 , and that growth stimulatory effects of physiological concentrations of IGF 1 and pharmacological concentrations of insulin are probably mediated through the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A large proportion of alpha DFMO arrested cells can be induced to progress to S phase by insulin ( 1 microM , acting via IGF 1 receptor ) plus putrescine in a serum free medium ( greater than or equal to 50 % of FCS effect ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cross linking of 125I insulin and 125I IGF 1 to their receptors , using disuccinimidyl suberate ( DSS ) , and identification of the receptor with sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography showed a band with a molecular mass of 135 kDa , probably corresponding to the alpha subunit of the insulin receptor and a major band with a molecular mass of 145 kDa for the alpha subunit of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Despite this high level of IGF 1 binding it is unlikely that non classical insulin binding represents insulin binding to an IGF 1 receptor because 1 ) anomalous binding is 30 times greater than that predicted from cross specificity , 2 ) low concentrations of unlabeled IGF 1 increase IGF 1 binding to the IGF 1 binding site but do not increase IGF 1 binding to the non classical insulin binding site and 3 ) the IGF 1 receptor ' s affinity for insulin ( and IGF 1 ) increases greatly during receptor purification . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of insulin on ovarian cells are mediated possibly through binding of the peptide to its own receptor or to the IGF 1 receptor ( the specificity spillover phenomenon ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockade of the IGF 1 receptor of cytotrophoblasts with alpha IR 3 , a monoclonal anti IGF 1 receptor antibody , prevented the suppression of aromatase activity by IGF 1 , but did not alter insulin ' s inhibitory effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our experiments using blocking antibodies to the IGF 1 receptor confirm that the Class 2 mitogens all act by binding to IGF 1 receptors . ^^^ Thus , growth factor induced DNA synthesis in WI 38 cells is apparently mediated by the glucocorticoid receptor ( Class 3 ) , the IGF 1 receptor ( Class 2 ) , and most interestingly any one of several Class 1 growth factor receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In one new approach , it has been noted that the 11E8 TBIAb can precipitate the phosphorylated beta subunit of the insulin and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By analogy to other biologic systems , these effects of insulin and of IGF 1 are probably mediated by occupancy of the IGF 1 receptor , which is cross occupied by insulin at superphysiologic concentrations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Serum from a patient with circulating autoantibodies to the insulin receptor competes for insulin but not IGF 1 binding , whereas alpha IR 3 , a monoclonal antibody directed toward the human IGF 1 receptor inhibits IGF 1 but not insulin binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Antibodies to deduced sequences of the insulin receptor distinguish conserved and nonconserved regions in the IGF 1 receptor . ^^^ An antibody directed to a cytoplasmic domain near the membrane spanning region of the proreceptor inhibited the protein tyrosine kinase activity of both receptors whereas an antibody directed to the C terminus of the insulin receptor showed no cross reactivity with the IGF 1 receptor . ^^^ The results establish that the cloned cDNA from the human placenta encodes the insulin receptor and not the closely related IGF 1 receptor , that the IGF 1 and insulin receptors share a specific amino acid sequence necessary for the expression of enzymatic activity , and that the C terminus of the insulin receptor is not conserved in the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tyrosine specific protein kinases have been reported to be associated with the transforming gene product of RNA tumor viruses , the EGF receptor , the IGF 1 receptor and a protein believed to be the receptor for PDGF . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These data indicate that rat bone cells possess a specific receptor for IGF 1 with binding characteristics similar to those reported in human fibroblasts , and that IGF 1 receptor concentrations are increased by exposure to glucocorticoids . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity cross linking of 125I IGF 2 to the Mr = 250 , 000 type 2 IGF receptor structure in rat liver membranes was blocked by the anti receptor Ig , while no effect on affinity labeling of insulin receptor with 125I insulin or IGF 1 receptor with 125I IGF 1 or 125I IGF 2 was observed . ^^^ Rat hepatoma H 35 cells contain insulin and IGF 2 receptor , but not IGF 1 receptor , and respond half maximally to insulin at 10 ( 10 ) M and to IGF 2 at higher concentrations with increased cell proliferation ( Massague , J . , Blinderman , L . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These findings in both placenta and fetal brain membrane are consistent with the proposed heterotetrameric structure of the Sm C / IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study examines 125I labeled insulinlike growth factor 1 ( IGF 1 ) binding to patient ' s and control fibroblasts . 125I labeled IGF 1 binds to a specific IGF 1 receptor in normal fibroblasts . ^^^ The ability of the patient ' s IGF 1 receptor to recognize insulin also appears to be altered . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since insulin and proinsulin are structurally homologous to IGF 1 , we investigated the ability of insulin analogues to compete for occupancy and to directly modulate IGF 1 receptor concentrations . ^^^ Bovine proinsulin and guinea pig insulin competed less potently than porcine insulin for the IGF 1 receptor , and produced receptor loss in proportion to their ability to occupy the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These studies indicate , therefore , that this monoclonal antibody binds preferentially to the insulin receptor but also crossreacts to a lesser extent with the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Early in gestation , a high concentration of a low affinity IGF 1 receptor was found . ^^^ After approximately the 17th wk of gestation a higher affinity IGF 1 receptor appeared , which then increased in concentration . ^^^ Around midgestation a separate IGF 1 receptor , indicated by the preferential displacement of iodinated IGF 1 by IGF 1 , appeared . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The close correspondence between an approximate 50 % effective dose ( ED 50 ) of phosphorylation and an approximate Kd for IGF 1 binding leads us to conclude that a high affinity IGF 1 receptor , not the structurally similar insulin receptor , is the mediator of IGF 1 stimulated kinase activity . ^^^ Immunoprecipitation indicates that both the beta subunit of the IGF 1 receptor and the beta subunit of the insulin receptor are targets for the IGF 1 stimulated protein kinase . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Control fibroblasts exhibited the usual affinity labeling of the disulfide linked Mr = 350 , 000 insulin and IGF 1 receptor structures . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that CC 139 cells possess at least two types of IGF receptors , an insulin insensitive IGF receptor with high affinity for MSA which apparently mediates its biological effect , and an insulin sensitive IGF 1 receptor . ^^^ Insulin appears to exert its mitogen potentiating activity in CC 139 fibroblasts by interacting with the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin and IGF 1 receptor proteins , like the receptor proteins for other growth promoting hormones such as EGF and PDGF , are closely associated with tyrosine specific protein kinase activities . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To identify injury responsive factors and cells , we examined the mRNAs for the following factors and some of their receptors : basic and acidic fibroblast growth factors ( bFGF , aFGF ) and FGF receptor 1 ( FGFR 1 ) ; ciliary neurotrophic factor ( CNTF ) and CNTF receptor alpha ( CNTFR alpha ) ; brain derived neurotrophic factor ( BDNF ) and its receptor trkB ; and insulin like growth factor 1 ( IGF 1 ) and IGFR 1 receptor ( IGF 1R ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor is highly expressed in SMCs in intact arteries and in cultured SMCs and is activated by binding of IGF 1 to the two alpha subunits . ^^^ Insulin and IGF 2 from the circulation can interact with the IGF 1 receptor at higher concentrations . ^^^ Insulin receptors are few or absent in SMCs and circulating insulin concentrations in vivo are probably too low for a direct action of insulin on the IGF 1 receptor in SMCs . ^^^ The effects of IGF 1 receptor activation on signal transduction pathways ( eg , the MAP kinase cascade ) implicated in DNA synthesis and proliferation are weak and this correlates with the meager mitogenic activity of IGF 1 in SMC . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Finally , specific changes occur in renal GH binding protein ( GHBP ) mRNA , IGF 1 receptor mRNA , and IGFBP mRNA expression in long term diabetes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mitogenic potential of insulin on lymphoma cells lacking IGF 1 receptor . ^^^ We have characterized an insulin dependent T cell lymphoma , LB , devoid of IGF 1 receptor , which undergoes insulin stimulation and cell proliferation both in vitro and in vivo . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The proximal promoter region of the rat IGF 1 receptor gene contains multiple Sp 1 consensus binding sites ( GC boxes ) . ^^^ Taken together , these results demonstrate that Sp 1 can regulate expression of the IGF 1 receptor promoter by acting both on GC boxes in the 5 ' flanking region of the promoter and on a CT element in the 5 ' untranslated region . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) binding proteins ( IGFBPs ) potently modulate the interactions of IGF 1 and 2 with the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine the effects of acute myocardial infarction on the expression of insulin like growth factor 1 ( IGF 1 ) and insulin like growth factor 1 receptors ( IGF 1R ) on the surviving myocytes of the left and right ventricles , large infarcts were produced in rats and the animals sacrificed 2 days later . ^^^ In order to establish whether the upregulation of IGF 1 and IGF 1R with infarction was coupled with induction of late growth related genes , which are known to be implicated in DNA replication and mitotic division , proliferating cell nuclear antigen ( PCNA ) and histone H 3 expression was assessed by Northern blot and RTPCR . ^^^ In conclusion , acute myocardial infarction is associated with enhanced expression of IGF 1 and IGF 1R on stressed myocytes , and this phenomenon may activate genes essential for DNA synthesis , possibly affecting myocyte growth . ^^^ Upregulation of IGF 1 , IGF 1 receptor , and late growth related genes in ventricular myocytes acutely after infarction in rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This stimulation occurred via an IGF 1 receptor independent mechanism because both [ QAYL ] IGF 1 ( an IGF 1 analogue with decreased affinity for the IGFBPs but normal affinity for the IGF 1 receptor ) and alpha IR 3 ( a blocking monoclonal antibody against the IGF 1 receptor ) had no effect on IGF 1 stimulated increases in IGFBPs . ^^^ These data suggest that the production of IGFBPs in human RPE cells is regulated by distinct mechanisms which include ( 1 ) an IGF 1 receptor independent interaction of IGF 1 with secreted IGFBPs and ( 2 ) de novo synthesis of IGFBPs by serum containing factors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) dependent phosphorylation of the IGF 1 receptor in MG 63 cells . ^^^ Insulin like growth factor 1 ( IGF 1 ) stimulates multiplication of the human osteosarcoma cell line , MG 63 . by acting through the IGF 1 receptor . ^^^ We have characterized IGF 1 stimulated phosphorylation of the IGF 1 receptor in this cell line . ^^^ Further immunoprecipitation with IGF 1 receptor monoclonal antibodies ( alpha IR 3 , 18E9 ) and analysis by sodium dodecylsulfate polyacrylamide gel electrophoresis and autoradiography demonstrated IGF 1 dependent autophosphorylation of the IGF 1 receptor . ^^^ Phosphoamino acid analysis of the IGF 1 receptor beta subunit and the observation that antiphosphotyrosine Agarose did not immunoprecipitate [ 35S ] methionine labeled receptor from unstimulated cells , demonstrated that in the absence of IGF 1 , the receptor was not phosphorylated on tyrosine residues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin ( 10 ( 5 ) mol / L ) , which binds to the IGF 1 receptor , but not to the IGF 2 receptor or IGFBPs , displaced 39 + / 8 % of [ 125I ] IGF 1 binding in glomeruli , 60 + / 7 % in the tubulo interstitial cortex , and 32 + / 7 % in the medulla . ^^^ In summary , [ 125I ] IGF 1 binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF 1 receptor in the tubulo interstitial cortex , with binding in the medulla more evenly divided . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF binding protein 5 and IGF 1 receptor regulation in hypophysectomized rat kidneys . ^^^ The lower molecular mass protein , which has been identified as the alpha subunit of the IGF 1 receptor , and the higher molecular mass species were both upregulated by HYPX . ^^^ Adaptations in the kidney after HYPX include an upregulation of the IGF 1 receptor as well as IGFBP 5 . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thiol redox reactions are known to play a role in regulating conformational changes in the insulin receptor and possibly also in the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to analyze the presence and the function of the `` insulin like growth factor 1 ( IGF 1 ) system ' ' in human non small cell lung cancer ( N SCLC ) we tested 5 cell lines of different histological sub types : A 549 , Ca Lu 6 , SK Lu 1 ( adenocarcinoma ) ; Ca Lu 1 , SK Mes 1 ( squamous carcinoma ) and one normal fibroblast like fetal lung cell line ( IMR 90 ) for expression of the IGF 1 peptide and its RNA transcribed from the IGF 1 gene ; IGF binding proteins ( IGF BP ) ; IGF 1 receptor ( IGF 1 R ) and its mRNA . ^^^ Finally , by thymidine uptake and colorimetric metabolic MTT assays , we found that most neoplastic cell lines react mitogenically to IGF 1 and that its physiological effect is abolished by an anti IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined the relationship between signal transduction and the expression of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor level , and IGF binding proteins ( IGFBPs ) in murine clonal osteoblastic MC3T3 E 1 cells . 12 O Tetradecanoylphorbol 13 acetate ( TPA ) , an activator of protein kinase C , decreased the secretion of immunoreactive IGF 1 into the medium , whereas dibutyryl cAMP ( Bt2cAMP ) augmented the secretion . ^^^ In contrast , Bt2cAMP affected neither IGF 1 receptor number nor the IGFBP secretion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that proteins corresponding to the two alternatively spliced human IGF 1 receptor transcripts are biologically active , but have distinct signaling properties . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The cell lines expressed luteinizing hormone receptor ( LH R ) ( a Leydig cell specific gene ) , insulin like growth factor 1 , insulin like growth factor 1 receptor ( IGF 1 R ) and insulin like growth factor binding protein 2 ( IGFBP 2 ) genes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 analogues with high affinity for the IGF 1 receptor and weak affinity for IGFBP paradoxically evoked a small increase in IGFBP 4 , probably through a general increase in protein synthesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Only upon treatment with pharmacological doses of insulin ( 1 microM ) , probably through IGF 1 receptor , did luciferase activity increase 4 . 3 + / 0 . 4 , 3 . 2 + / 0 . 4 and 3 . 5 + / 0 . 5 fold when transfected with 136 LUC , 110 LUC and 67 LUC plasmids , respectively ; there was no increase with 19 LUC . ^^^ These results indicate that the increased promoter activities observed are probably mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To elucidate this , the present study was undertaken to determine the presence and cellular distribution of IGF 1 , IGF 1 receptor ( IGF IR ) , and IGF binding proteins ( IGFBP ) 1 4 in human fallopian tubes during various reproductive stages , by means of immunohistochemical analysis with specific antibodies to IGF 1 , IGF IR and IGFBPs 1 4 . ^^^ There were also no differences in immunoreactivity of IGF 1 , IGF IR , and IGFBPs 1 4 present in ampullary vs . isthmus region of the tubes . ^^^ The immunostaining intensity of IGF 1 , IGF IR , and IGFBPs in fallopian epithelial cells was cycle dependent and considerably higher in late proliferative and early mid secretory compared to late secretory phases , with little immunostaining in the early proliferative phase of the menstrual cycle and postmenopausal period . ^^^ In summary , the immunohistochemical study reported here demonstrates the presence of IGF 1 , IGF IR , and IGFBPs 1 4 in the human fallopian tube during various reproductive stages . ^^^ Immunohistochemical localization of insulin like growth factor ( IGF 1 ) , IGF 1 receptor , and IGF binding proteins 1 4 in human fallopian tube at various reproductive stages . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using stably transfected NIH 3T3 cell lines , we now show that mutation of the analogous residues in the IGF 1 receptor abolishes all short , intermediate , and long term responses to IGF 1 . ^^^ Additionally , we have identified two parameters , induction of c fos gene expression and ornithine decarboxylase enzyme activity , which are extremely sensitive to IGF 1 stimulation and which will be particularly useful in evaluating the biological activity of other mutated versions of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These modifications dramatically reduce the ability of these analogues to bind to IGFBPs although they remain active at the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis of the interaction of IGF 1 analogs with the IGF 1 receptor and IGF binding proteins . ^^^ Distinct domains of IGF 1 are important for maintaining high affinity for the IGF 1 receptor and for the various species of IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The lower molecular weight species has been identified previously as the alpha subunit of the IGF 1 receptor and was upregulated by a 6 % LP diet . ^^^ The upregulation of the IGF 1 receptor was evident on 12 % polyacrylamide gels of both glomeruli and basolateral membranes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We therefore investigated the action of TGF beta 1 on the different components of the IGF system , namely , IGF 1 , 2 , IGF binding proteins ( IGFBPs ) and IGF 1 receptor present in testicular Leydig cells . ^^^ Affinity labeling of these receptors by covalently binding them to 125I IGF 1 with disuccinimidyl suberate and subsequent electrophoretic analysis of the labeled complex revealed that the inhibitory action of TGF beta 1 ( 2 ng / ml , 72 h ) occurs at the level of a 135 kDa protein which represents the classical form of the binding subunit of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Signal transduction pathways stimulated by insulin or insulin like growth factor 1 ( IGF 1 ) were compared in transfected NIH3T3 fibroblast cell lines expressing the human insulin receptor , IGF 1 receptor , or a chimeric IGF 1 receptor with its carboxy terminal tail replaced with that of the insulin receptor ( approximately 1 10 10 ( 6 ) receptors / cell ) . ^^^ The chimeric receptor stimulated significantly lower levels of phosphorylation of several proteins relative to the wild type IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The objective of the present study was to elucidate the presence and cellular distribution of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor ( IGF IR ) , and IGF binding proteins ( IGFBPs ) in human uterine tissue at various reproductive stages , and to determine the effect of IGF 1 and its interaction with epidermal growth factor ( EGF ) and platelet derived growth factor ( PDGF ) in endometrial stromal and myometrial smooth muscle cells in primary culture . ^^^ Using specific antibodies , immunohistochemical observations indicated that luminal and glandular epithelial cells were the major sites of immunoreactive IGF 1 , IGF IR , and IGFBPs 1 4 , followed by myometrial smooth muscle and endometrial stromal cells . ^^^ The immunostaining intensity of IGF 1 , IGF IR , and IGFBPs in endometrial but not myometrial tissue was cycle dependent and higher in the late proliferative and early / mid secretory periods than in the late secretory and postmenopausal periods , with little immunostaining at the early proliferative phase of the menstrual cycle . ^^^ Stromal and smooth cells in primary cell culture also contained immunoreactive IGF 1 , IGF IR , and IGFBPs . ^^^ The results indicate that human uterine tissue at various reproductive stages contains immunoreactive IGF 1 , IGF IR , and IGFBPs 1 4 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study was therefore undertaken to investigate the interaction of IgGs extracted from the sera of patients with Graves ' disease , with or without overt ophthalmopathy , with respect to IGF 1 receptor binding sites on fibroblasts from human orbital tissue . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , when expression of the IGF 1 receptor was analyzed by the Northern blot assay , we found that H 59 cells expressed significantly higher levels of mRNA transcripts encoding IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , the levels of IGF 1 receptor mRNA and 125I labelled IGF 1 binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys . ^^^ On the other hand , both the levels of IGF 1 receptor mRNA and 125I labelled IGF 1 binding were increased ( approximately 2 . 5 fold ( after 24 h ) and approximately 3 fold ( after 48 h ) respectively ) in prepubertal animals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our results show significantly increased levels of IGF mRNA in old healthy and BPH affected subjects ; the respective rises for IGF 1 , IGF 2 , and IGF 1 receptor mRNAs were 3 . 0 , 2 . 9 , and 1 . 5 fold ( BPH ) and 2 . 7 , 2 . 4 , and 1 . 8 fold ( old normal controls ) . ^^^ Together , these observations suggest that prostatic adenomas may result from at least two conjugate processes : one characterized by a drop in the mRNA levels of steroid hormone receptors , which might be associated with a lower epithelium / stroma ratio , and another characterized by normal aging phenomena , of which the increased production of IGFs and IGF 1 receptor transcripts could be biochemical markers . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis of the interaction of insulin like growth factor 1 ( IGF 1 ) analogs with the IGF 1 receptor and IGF binding proteins . ^^^ Distinct domains of IGF 1 are important for maintaining high affinity for the IGF 1 receptor and for the various species of IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunoprecipitation against phosphorylated tyrosine indicated that IGF 1 dependent autophosphorylation of IGF 1 receptor beta subunit was inhibited by simultaneous TGF beta stimulation . ^^^ These observations demonstrate that TGF beta acts synergistically with IGF 1 and regulates the IGF 1 autocrine / paracrine axis via a complex regulatory mechanism with decreased production of IGF 1 and IGFBPs and dephosphorylation of IGF 1 receptor , whereas there is an apparent up regulation of the binding of [ 125I ] IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor in src transformed cells . ^^^ It has not been clear , however , whether src induced phosphorylation altered the enzymatic or signaling properties of the IGF 1 receptor and thus whether the IGF 1 receptor could be a functionally significant target for pp60v src . ^^^ To examine the effect of src expression on the activity of the IGF 1 receptor , the human IGF 1 receptor was expressed in Rat 1 fibroblasts co expressing the temperature sensitive 5 src mutant , tsLA 29 . ^^^ The IGF 1 receptor exhibited an elevated level of tyrosine phosphorylation in src transformed cells even in the absence of IGF 1 treatment . ^^^ A kinase defective mutant of the IGF 1 receptor also became constitutively phosphorylated in src transformed cells , ruling out a possible autocrine mechanism for this phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of ethanol on IGF 1 receptor and insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation was determined by immunoprecipitation and Western blotting , as was the phosphatidylinositol 3 kinase content within IRS 1 immunoprecipitates . ^^^ The inhibition of IGF 1 mediated cell proliferation was accompanied by abrogation of IGF 1 receptor tyrosine autophosphorylation . ^^^ CONCLUSIONS : The data indicate that physiologically relevant concentrations of ethanol inhibit the responses of glial cells to IGF 1 , including IGF 1 receptor autophosphorylation , IRS 1 and phosphatidylinositol 3 kinase activation , and cell growth . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To circumvent this difficulty , QAYL , an IGF 1 analog that binds to the IGF 1 receptor but not to IGF binding proteins , was used . ^^^ QAYL increased LDL receptor number 56 72 % with half maximum effect at 0 . 6 ng / ml . alpha IR 3 , a monoclonal antibody directed toward the IGF 1 receptor , blocked this effect . ^^^ IGF 1 , acting through the IGF 1 receptor and modulated by IGF binding proteins , may contribute to the regulation of LDL metabolism by increasing translation of LDL receptor message . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Role of GH and IGF 1 in the regulation of IGF 1 , IGF 1 receptor and IGF binding protein gene expression in the rat spleen . ^^^ There were no changes in GH receptor or IGF 1 receptor mRNA levels in Hx or bGH or rhIGF 1 treated animals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To evaluate the molecular mechanism of these effects we studied the effect of hypophysectomy ( Hx ) and GH replacement therapy on the expression of IGF 1 , the IGF 1 receptor and IGF binding protein 2 ( IGFBP 2 ) in juvenile rats . ^^^ IGF 1 mRNA levels were reduced 30 % by Hx , IGFBP 2 mRNA levels fell 50 % whereas IGF 1 receptor mRNA levels were unaffected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The reduced growth factor requirements of murine fibroblasts transformed by simian virus 40 ( SV 40 ) have been attributed to insulin like growth factor ( IGF ) 1 induction by T antigen and consequent activation of IGF 1 receptor signaling . ^^^ The present study shows that the autonomous growth of SV 40 transformed human fibroblasts also requires type 1 IGF 1 receptor activation but that this is not due to de novo induction of IGF 1 gene expression since untransformed human fibroblasts , which fail to proliferate in the absence of serum , also showed IGF 1 gene expression under serum free conditions . ^^^ These findings suggest that loss of IGFBP 5 in SV 40 transformed fibroblasts facilitates interaction of endogenously produced IGF 1 with the IGF 1 receptor and increases their sensitivity to autocrine stimulation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
From 8 40 days postinoculation ( dpi ) , spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin like growth factor 1 ( IGF 1 ) , IGF binding protein 2 ( IGFBP 2 ) , IGF 1 receptor ( IGFR 1 ) , glial fibrillary acidic protein ( GFAP ) , and myelin basic protein ( MBP ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Erythrocyte IGF 1 SB showed a significant decrease by 6 months secondary to a decrease in IGF 1 receptor number , with no change in affinity . ^^^ The 6 month IGF 1 receptor binding correlated inversely with the increase in IGF 1 ( r = 0 . 88 ; P < 0 . 001 ) . ^^^ Erythrocyte IGF 1 SB at baseline did not correlate with the growth response , although there was an inverse trend between the 6 month IGF 1 receptor level and the growth rate . ^^^ IGF 1 and IGFBP 3 show progressive increases , whereas the erythrocyte IGF 1 receptor binding capacity decreases by 6 months , and GHBP shows little change during the first year of GH treatment . ^^^ Data from this study suggest that changes in IGFBP 3 and , to a lesser extent , IGF 1 are the major correlates of growth rate , and that down regulation of the IGF 1 receptor may have relatively little influence on growth rate compared with changes in IGFBP 3 and IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Des ( 1 3 ) IGF 1 is a naturally occurring IGF 1 analog with markedly reduced affinity for IGFBPs but with an affinity for the IGF 1 receptor that is comparable to that for native IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Levels of IGF 1 receptor and its mRNA were highest at perinatal ages and steadily decrease thereafter , although a partial recovery in IGF 1 receptor mRNA was found in adults . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The high affinity binding of IGF 1 and competition by insulin suggested that the [ 125I ] IGF 1 binding was to an IGF 1 receptor rather than to a membrane associated IGFBP , to which insulin does not bind . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In vitro , IGF 1 receptor mediated actions increased both steroidogenesis and DNA synthesis . ^^^ Insulin stimulated DNA synthesis at concentrations appropriate to cross react with the IGF 1 receptor , and this effect was greater in a testicular interstitial Leydig cell depleted cell population compared with a Leydig cell enriched cell culture . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine the impact of skeletal unloading on IGF 1 production and function , we assessed the mRNA levels of IGF 1 and its receptor ( IGF IR ) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation . ^^^ The mRNA levels for IGF 1 and IGF IR rose during hindlimb elevation , returning toward control values during recovery . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , transcripts for the IGF 1 receptor were evident in freshly isolated rat bone marrow cells and showed a 50 % down regulation during differentiation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The contribution of binding to the IGF 1 receptor was estimated by competition with unlabeled IGF 1 , IGF 2 , and insulin . ^^^
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Jejunal mRNA content for IGF 1 , IGF 1 receptor , and IGF binding proteins 3 and 4 ( IGFBP 3 , 4 ) were determined by Northern blotting . ^^^
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These findings indicate that Crk 2 is an endogenous substrate of the IGF 1 receptor tyrosine kinase and provide the first demonstration that a mitogenic growth factor induces tyrosine phosphorylation of endogenous c Crk . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptor mRNA and IGF 1 receptor mRNA were both present and showed a similar , widespread pattern throughout retina development . ^^^ These findings suggest a near constitutive expression of insulin receptor and IGF 1 receptor genes , while IGF 1 and IGFBP 5 showed a highly focal spatiotemporal regulation of gene expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine whether this microglial response upregulates astrocytic expression of IGF related proteins , we induced EAN and used in situ hybridization and immunocytochemistry to examine the mRNAs and peptides for glial fibrillary acidic protein ( GFAP ) , insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor ( IGFR 1 ) and IGF binding protein 2 ( IGFBP 2 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The human insulin like growth factor ( IGF ) binding protein 3 inhibits the growth of fibroblasts with a targeted disruption of the IGF 1 receptor gene . ^^^ We have asked whether the IGFBP 3 has an effect on cell growth , which is independent of its ability to bind IGF 1 and thus inhibit the activation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Solution hybridization RNAase protection assays showed that renal IGF 1 mRNA , IGF 1 receptor ( IGF 1R ) mRNA , and IGF binding protein 1 ( IGFBP 1 ) mRNA were unaffected by exogenous IGF 1 , but this treatment significantly increased renal IGF 1 in ARF rats compared with normal rats and ARF rats not receiving IGF 1 . ^^^ After ARF renal mRNA for IGF 1 was decreased , IGF 1R was unchanged and IGFBP 1 was increased . ^^^ Insulin like growth factor 1 ( IGF 1 ) enhances recovery from HgCl 2 induced acute renal failure : the effects on renal IGF 1 , IGF 1 receptor , and IGF binding protein 1 mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Messenger RNA and peptide distributions of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor ( IGFR 1 ) , IGF binding protein 2 ( IGFBP 2 ) , glial fibrillary acidic protein ( GFAP ) , and myelin basic protein ( MBP ) were studied 3 56 days after CI by in situ hybridization and immunocytochemistry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have previously shown that circulating progenitor cells in patients with polycythemia vera ( PV ) are hypersensitive to insulin like growth factor 1 ( IGF 1 ) with respect to erythroid burst formation in serum free medium , and that this effect occurs through the IGF 1 receptor . ^^^ To investigate the molecular basis of this IGF 1 hypersensitivity phenomenon , we examined tyrosine phosphorylation of the IGF 1 receptor beta subunit in peripheral blood mononuclear cells ( PBMNC ) from eight PV patients and six normals . ^^^ The IGF 1 receptor beta subunit was immunoprecipitated , and the protein was resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotted with antiphosphotyrosine antibody ( 4G10 ) . ^^^ We found that , in the absence of exogenous IGF 1 , there was a basal level of tyrosine phosphorylation of the IGF 1 receptor beta subunit , and it was substantially greater in PV than in normal . ^^^ In contrast , in PBMNC from three patients with erythrocytosis , no significant increase above normal was seen in either basal or induced tyrosine phosphorylation of the IGF 1 receptor beta subunit . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression in the kidney of the chronically hypoinsulinemic rat and hyperinsulinemic rat . ^^^ We studied IGF 1 and IGF 1 receptor gene expression in the kidney of rats with long standing STZ induced diabetes . ^^^ IGF 1 mRNA level in the chronically diabetic kidney was approximately 50 % of that in control rats , whereas IGF 1 receptor mRNA was increased approximately threefold . ^^^ Ten days ' treatment with insulin 65 days after induction of diabetes resulted in a glucose dependent decrease in IGF 1 receptor mRNA . ^^^ Chronic hyperinsulinemia with near normoglycemia did not change gene expression of either IGF 1 or IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , IGF 1 receptor mRNA abundance was unchanged . ^^^ However , plasma membrane IGF 1 receptor binding on day 2 and day 7 was near double the control values ( P < 0 . 01 ) . ^^^ In contrast to unchanged IGF 1 receptor mRNA levels , the abundance of mRNA levels of insulin like growth factor binding proteins ( IGFBP ) 2 , 3 , 4 and 5 fell approximately 14 to 62 % of control levels day 2 after injury ( P < 0 . 05 ) , suggesting reduced IGFBP production . ^^^ Thus , the renal response to ischemic ATN , namely , low IGFBP mRNA levels and high IGF 1 receptor number , may function to increase IGF 1 bioavailability and thereby enhance the reparative actions of local and circulating IGF 1 in ischemic ATN . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 2 ( IGF 2 ) is more potent than IGF 1 in stimulating cortisol secretion from cultured bovine adrenocortical cells : interaction with the IGF 1 receptor and IGF binding proteins . ^^^ Although both IGF receptors are present in adult bovine adrenocortical cells , the effect of IGF 2 seems to be mediated through interaction with the IGF 1 receptor , as [ Arg 54 , 55 ] IGF 2 , which only binds to the IGF 1 receptor , was equipotent to native IGF 2 , whereas [ Leu 27 ] IGF 2 , which preferentially binds to the type 2 IGF receptor , did not show any effect . ^^^ In conclusion , these results demonstrate that 1 ) IGF 2 stimulates basal as well as ACTH induced cortisol secretion from bovine adrenocortical cells more potently than IGF 1 ; 2 ) this effect is mediated through interaction of IGF 2 with the IGF 1 receptor ; 3 ) bovine adrenocortical cells synthesize various IGFBPs that are induced differentially by ACTH ; and 4 ) IGFBPs apparently play a modulatory role in IGF induced stimulation of adrenal steroidogenesis . ^^^ Therefore , bovine adult adrenocortical cells provide a useful tissue culture model in which the interactions among locally produced IGFs , IGFBPs , and the IGF 1 receptor can be evaluated . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In dexamethasone treated cells , the levels of IGF 1 receptor tyrosine phosphorylation and receptor associated phosphatidylinositol 3 kinase activity were increased . ^^^ Thus , distinct signaling pathways activated by the IGF 1 receptor in skeletal muscle cells are differentially regulated by dexamethasone . ^^^ Potentiation of IGF 1 action correlates with increased IGF 1 receptor associated phosphatidylinositol 3 kinase activity and tyrosine phosphorylation of Shc , but appears to be independent of activation of the IRS 1 / phosphatidylinositol 3 kinase signaling pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Likewise , the addition of insulin , which can not bind to IGFBPs , at supraphysiological concentrations that are adequate to activate the IGF 1 receptor resulted in a similar increase in migration . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have correlated the morphological features of 30 human thyroid carcinomas with the cellular localisation of insulin like growth factor 1 ( IGF 1 ) mRNA and IGF 1 receptor peptide using in situ hybridisation with digoxigenin labelled oligoprobes and immunohistochemistry . ^^^ Immunohistochemistry for IGF 1 receptor showed moderate positivity confined to the tumour epithelial cells in both follicular and the majority of papillary carcinomas . ^^^ However , in a subgroup of papillary carcinomas characterised by a diffuse stromal lymphoid infiltration ( n = 5 ) , the stromal cells showed a much stronger reactivity for IGF 1 mRNA than the tumour or background thyroid , and the tumour cells showed a uniformly high level of immunoreactivity for IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A flow cytometric method was used , with a biotinylated and functionally active IGF 1 analogue , namely des ( 1 3 ) IGF 1 , which binds well to IGF 1 receptor but poorly to IGF binding proteins , followed by phycoerythrin conjugated streptavidin ( PE SA ) staining . ^^^ Furthermore , the level of expression on resting CD4+ T lymphocytes was greater than on CD8+ cells , and the concentration of biotin des ( 1 3 ) IGF 1 required to demonstrate the binding to IGF 1 receptor on CD8+ cells ( 68 nmol / l ) was 200 fold higher than for CD4+ cells ( 0 . 34 nmol / l ) , indicating that most of the IGF 1 receptor on CD8+ cells represented lower affinity sites . ^^^ The level of IGF 1 receptor expression was increased several fold after concanavalin A stimulation on both CD4+ and CD8+ T cell subsets . ^^^ Kinetic analysis of the expression of IGF 1 receptor and its association with interleukin 2 receptors ( IL 2R ) following activation showed a similar pattern , with no significant differences in the ratio of IGF 1 receptor : IL 2R per cell during the 3 days of cell culture . ^^^ Our studies suggest that biological activities of IGF 1 include direct stimulation of immune cells , and that expression of IGF 1 receptor may have a role in regulation of T cell function . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor binding was highly specific and required at least 100 nM insulin to cause any displacement of the bound ligand . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor does seem to occupy a central role in these processes . ^^^ Whereas an overexpressed IGF 1 receptor is mitogenic for IGF 1 alone and is fully transforming and protects cells from apoptosis , the same can not be said for overexpressed EGF and PDGF receptors ( 205 , 206 ) . ^^^ An important distinction in this regard is that it is not so much an overexpressed IGF 1 receptor that is important in transformation but the lack of it that does not allow the transformed phenotype . ^^^ Returning to more basic questions , a mutational analysis of the IGF 1 receptor has shown that specific domains are involved in its mitogenicity or its ability to facilitate transformation and that these two processes can be separated at the level of the receptor itself . ^^^ Little is known about the mechanism ( s ) by which the IGF 1 receptor protects cells from apoptosis ; here again , some fundamental questions can be raised . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Brown adipose tissue constitutively expressed insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) mRNAs . ^^^
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The stimulatory effect of insulin and IGF 1 on 2 deoxyglucose uptake in GLUT 4 expressing oocytes occurred via activation of the IGF 1 receptor . 3 . ^^^
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DN was found to inhibit IGF 1 dependent phosphorylation of the artificial substrate poly ( Glu : Tyr ) 4 : 1 by intrinsic IGF 1 receptor kinase either from mouse cerebellum or from rat spinal cord . ^^^ IGF 1 dependent autophosphorylation of the IGF 1 receptor was also inhibited as a function of DN concentration ( 10 100 microM ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To elucidate the possible mechanism of glibenclamide on clonal growth , chondrocytes were incubated with the sulfonylurea and the IGF 1 receptor antibody alpha IR 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using polyclonal antibodies against four regions of the IGF 1 receptor , we searched for putative conformational changes occurring in purified receptors . ^^^ We studied the ability of the antipeptide antibodies to immunoprecipitate the native , ligand occupied , or autophosphorylated IGF 1 receptor . ^^^ These data demonstrate that the IGF 1 receptor undergoes an autophosphorylation induced conformational change detectable in the kinase domain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Interaction of the p 85 subunit of PI 3 kinase with the insulin receptor ( IR ) and the IGF 1 receptor ( IGF 1R ) was investigated using the two hybrid system by assessing for his 3 and lacZ activation in S . cerevisiae . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both responses were completely blocked after incubation with alpha IR 3 , an MAb to the IGF 1 receptor ( by analysis of variance , p = 0 . 015 between full response curves ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In skeletal muscle of rats with chronic renal failure , we observed reduced IGF 1 and IGF 1 mRNA levels , resistance to the rhIGF 1 induced suppression of protein degradation , and stimulation of protein synthesis , increased IGF 1 receptor mRNA and IGF 1 receptor number and impaired receptor tyrosine kinase activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor studies performed in erythrocytes to assess IGF 1 receptor status at target cell tissues are potentially useful for clinical studies , since tissue biopsies or cultures are not required . ^^^ By correcting cell age for creatine , we studied IGF 1 receptor status in 24 normal subjects ( 11 adults and 13 children , eight prepubertal and five pubertal ) and 33 patients with pathologic conditions ( five adult acromegalics , six children with pituitary dwarfism , and 22 type 1 diabetic children , 15 prepubertal and seven pubertal ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In Rat 1 fibroblasts , stimulation of mitogen activated protein ( MAP ) kinase via the IGF 1 receptor and the Gi coupled receptor for lysophosphatidic acid ( LPA ) , but not via the EGF receptor , is sensitive both to pertussis toxin treatment and to cellular expression of a specific G beta gamma subunit binding peptide . ^^^ IGF 1 receptor ) and classical G protein coupled receptors ( e . g . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our data indicate that the structure and processing of the Drosophila insulin proreceptor are somewhat different from those of the mammalian insulin and IGF 1 receptor precursors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that higher IGF 1 receptor numbers rather than higher circulating IGF 1 may be a contributing factor to goiter formation in Graves ' disease . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Their anabolic and growth promoting actions are mediated via the IGF 1 receptor , present in all cells apart from liver and adipose cells , which contains the homologous insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A monoclonal antibody directed against the IGF 1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF 1 but not IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In CHO cells stably increasing V922E IGF IR , both IRS 1 phosphorylation and the IRS 1 associated phosphoinositide 3 kinase activity were stimulated in the absence of IGF 1 to the level attained by 1 nM IGF 1 stimulation of wild type IGF IR , whereas the Ras mitogen activated protein kinase pathway was not activated under the same condition . ^^^ In these CHO cells , V922E IGF IR significantly stimulated glucose uptake but did not promote mitogenesis in the absence of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we demonstrate an association between the IGF 1 receptor and p 85 , Syp , and GAP , but not with PLC gamma in lysates of cells overexpressing the human IGF 1 receptor . ^^^ We further investigated these interactions using glutathione S transferase ( GST ) fusion proteins containing the amino terminal SH 2 domains of p 85 or GAP , or both SH 2 domains of Syp or PLC gamma to precipitate the IGF 1 receptor from purified receptor preparations and from whole cell lysates . p 85 , Syp , and GAP GSTs precipitated the IGF 1 receptor , whereas the PLC gamma GST did not . ^^^ Using phosphopeptides corresponding to IGF 1 receptor phosphorylation sites , we determined that the p 85 and Syp GST association with the IGF 1 receptor could be inhibited by a carboxyl terminal peptide containing pY 1316 and that the GAP GST association could be inhibited by a NPXY domain peptide . ^^^ The GAP GST binding site was confirmed by showing that a mutant IGF 1 receptor with a deletion of the NPXY domain including tyrosine 950 was poorly precipitated by the GAP GST . ^^^ We conclude that p 85 and Syp may bind directly to the IGF 1 receptor at tyrosine 1316 , and that GAP may bind to the IGF 1 receptor at and PLC gamma was not evident . p 85 , Syp , and GAP are potential modulators of IGF 1 receptor signal transduction . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using primers derived from the human IGF 1 receptor ( IGF IR ) DNA sequence , constitutive expression of IGF IR mRNA in porcine conceptuses throughout early pregnancy was demonstrated . ^^^ IGF 1 treatment did not alter mRNA expression of the IGF IR gene in conceptuses of either morphology . ^^^ These results demonstrate that transient expression of P450arom and P 45017 alpha genes in perimplantation porcine conceptuses , document the constitutive expression of the conceptus IGF IR gene , and support the involvement of endometrial IGF 1 in modulation of embryonic P450arom mRNA abundance . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reverse transcription PCR was then used to assess the relative abundance of mRNAs for actin , glyceraldehyde 3 phosphate dehydrogenase , Na+ , K ( + ) ATPase , Sp 1 , TATA box binding protein TBP , IGF 1 , IGF 2 , IGF 1 receptor , and IGF 2 receptor in embryos that developed in vivo and in vitro using KSOM / AA . ^^^
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Cortisol at 1 microM for 2 48 h did not alter IGF 1 receptor transcripts , as determined by Northern blot analysis and ribonuclease protection assay . ^^^
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To determine the role of the IGF 1 receptor in breast cancer cell growth , we stably transfected MCF 7 breast cancer cells with a construct encoding an antisense RNA complementary to the region surrounding the translation initiation site of the IGF 1 receptor messenger RNA ( mRNA ) . ^^^ Clones expressing the antisense RNA exhibited a 30 % reduction in endogenous IGF 1 receptor mRNA levels and a significant reduction in receptor protein levels , as measured by both ligand binding assays and Western blot analysis . ^^^ These results strongly support a role for the IGF 1 receptor in the proliferation of human breast cancer cells and suggest that strategies using this type of technology may prove useful in cancer therapy . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , we determined the relative content of insulin / IGF 1 receptor hybrids in both tissues . ^^^ Renal cell carcinoma and adjacent normal tissue revealed similar amounts of insulin / IGF 1 receptor hybrids , i . e . , 44 + / 8 . 2 % of tracer IGF 1 binding in normal tissue and 46 + / 12 . 0 % in renal cell carcinoma . ^^^ When equal amounts of insulin and IGF 1 receptor protein were studied , we found significantly increased receptor autophosphorylation and elevated substrate phosphorylation in carcinoma tissue . ^^^ Our experiments show that renal carcinoma expresses an elevated amount of insulin and IGF 1 receptor protein with increased specific autophosphorylation and tyrosine kinase activity each . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
For this purpose , we stably transfected plasmids expressing mutant and wild type receptors into R cells , which are 3T3 like cells , derived from mouse embryos with a targeted disruption of the IGF 1 receptor genes , and therefore devoid of endogenous IGF 1 receptors . ^^^ These experiments show that the 1251 tyrosine residue is required for the transforming activity of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Chondrocyte IGF 1 receptor expression and responsiveness to IGF 1 stimulation in mouse articular cartilage during various phases of experimentally induced arthritis . ^^^ METHODS In situ IGF 1 receptor expression and responsiveness to IGF 1 stimulation were examined in murine articular cartilage at different phases in two models of experimentally induced arthritis . ^^^ IGF 1 receptor expression was visualised in joint sections with the use of anti IGF 1 receptor antibodies and quantified by confocal laser scanning microscopy . ^^^ Shortly after induction of arthritis , IGF 1 receptor expression initially declined , but it had returned to normal levels by day 1 and remained increased thereafter . ^^^ CONCLUSION The distribution of IGF 1 receptor expression in the different zones of normal articular cartilage reflects IGF 1 stimulation and metabolic activity of chondrocytes in these layers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To evaluate the effects of estrogen on the rat pituitary insulin like growth factor ( IGF ) system , binding of [ 125I ] IGF 1 and in situ hybridization for IGF 1 , the IGF 1 receptor and IGF binding protein 2 ( IGFBP 2 ) were coupled with quantitative autoradiography . ^^^ IGF 1 receptor messenger RNA ( mRNA ) was distributed diffusely through the anterior pituitary and was not different between the respective gonadectomized and estrogen treated groups . ^^^ In the neural lobe , [ 125I ] IGF 1 binding , IGFBP 2 mRNA , IGF 1 receptor mRNA , and IGF 1 mRNA were all uniformly distributed and did not differ between groups . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , both the IGF 1R / IR C 3 ' chimera and another chimera ( C 13 ' ) displayed high affinity binding properties for IGF 1 , which suggests distinct locations for major insulin and IGF 1 binding determinants in their respective receptors , in agreement with our previous findings ( Schumacher , R . , Mosthaf , L . , Schlessinger , J . , Brandenburg , D . , and Ullrich , A . ( 1991 ) J . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
While it has been demonstrated that this tyrosine kinase activity is necessary for the action of a number of transmembrane tyrosine kinase receptors , no evidence of this type has been adduced to date with respect to the signaling requirement of the IGF 1 receptor . ^^^ We have now shown that stably transfected NIH 3T3 cell lines overexpressing human IGF 1 receptors display increased responses to IGF 1 and an IGF 1 mimetic antibody , alpha IR 3 , in terms of short , intermediate , and long term actions initiated by activation of the IGF 1 receptor . ^^^ These results indicate that , for all parameters tested , the tyrosine kinase activity of the IGF 1 receptor is necessary for activation of the IGF 1 stimulated signal transduction cascade . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although specific receptors for each factor have been identified , blocking experiments using a mAb against IGF 1 receptor showed almost complete abolishment of the enhancing effect of these factors , indicating that the enhancing effect is exhibited via the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Normal freshly collected lymphocytes expressed mRNAs for both IGF 1 receptor and IGF 2 receptor but no expression of the corresponding growth factors was detectable . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Growing oocytes in infant and mature ovaries expressed transcripts for IGF 1 and IGF 2 , respectively , and all oocytes expressed abundant IGF 1 receptor transcripts , raising the possibility of autocrine IGF function in oocyte maturation . ^^^ IGF 1 receptor mRNA was abundant in GC of antral and atretic follicles , and was expressed at low levels in the thecal and interstitial compartments . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The electrophoretic migration of cross linked 125I IGF 1 to microsomal membranes revealed a complex with M ( r ) = 130 , 000 under reducing conditions corresponding to the alpha subunit of the IGF 1 receptor . ^^^
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Alternatively , the association of IGF 2 with another IGFBP would inhibit this binding and lead to its autocrine or intracrine mitogenic action via the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Oestrogen stimulates the expression of IGF 1 and IGF 1 receptor mRNAs , whereas progesterone induces the major endometrial IGFBP , IGFBP 1 , which is proposed to act as an inhibitor of IGF actions in normal endometrium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , the determinants of IGF 2 binding to IGFBPs partially overlap those for the IGF II / mannose 6 phosphate receptor and overlap those for the IGF 1 receptor to a lesser extent . ^^^
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Pretreatment of MDA MB 468 and MDA MB 231 cells with IGF 1 receptor antibody ( alpha IR 3 ) blocked the IGF 1 effect on IGFBP 3 levels in the media in both cell lines and IGFBP 2 and IGFBP 5 secreted levels in MDA MB 468 cell conditioned media . ^^^
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BACKGROUND : This study determined whether the resistance to the mitogenic effect of insulinlike growth factor 1 ( IGF 1 ) in AGS ( we found that IGF 1 had almost no effect on the growth of AGS ) cells is caused by the absence of IGF 1 receptor on the cells or by the interference of endogenous IGFs and IGF binding protein ( IGFBP ) . ^^^
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All NHM cells and mesothelioma cell lines expressed IGF 1 , IGF binding protein 3 ( IGFBP 3 ) , and IGF 1 receptor mRNA by either Northern blot or reverse transcription polymerase chain reaction analysis . ^^^ Exogenous recombinant IGF 1 stimulated cell proliferation of NHM cells , demonstrating the presence of a functional IGF 1 receptor . ^^^
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Overexpression of the IGF 1 receptor did not affect sensitivity or maximal responsiveness of glucose uptake or PI 3 kinase activation to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using both neuron and glial enriched cultures obtained from fetal rat hypothalami we found that addition of beta E 2 elicited a significant increase in IGF 1 receptor levels in neurons , without affecting its affinity . ^^^
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IGF 2 and IGF IIE 21 stimulated DNA synthesis via the IGF 1 receptor , whereas the IGF II / Man 6 P receptor mediated their rapid internalization and inactivation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor levels and the proliferation of young and senescent human fibroblasts . ^^^ We have investigated the role of the IGF 1 receptor in the proliferation of young and senescent human diploid fibroblasts . ^^^ Using WI 38 cells , we have established the following : 1 ) both young and senescent cells have IGF 1 receptors , which can be autophosphorylated by IGF 1 , the intensity of the autophosphorylation being roughly the same in both types of cells ; 2 ) the levels of IGF 1 receptor mRNA are also similar in young and senescent cells ; 3 ) both young and senescent cells have an absolute requirement for the IGF 1 receptor in order to be stimulated by either serum or SV 40 , respectively ; 4 ) despite these similarities , young cells respond to IGF 1 ( in combination with other growth factors ) with DNA synthesis and mitosis , and senescent cells do not . ^^^ We conclude that , although the IGF 1 receptor is still needed by senescent cells for a growth response to SV 40 , it is not , by itself , the determinant of senescence , at least in WI 38 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Exposure of rat GC pituitary cells to insulin like growth factor 1 ( IGF 1 ) resulted in a time and concentration dependent reduction in cell surface IGF 1 receptor binding . ^^^ Scatchard analysis revealed that the number of IGF 1 cell surface receptors decreased from 18 , 500 to 9 , 100 sites / cell , with no apparent alteration in the affinity of IGF 1 receptor for its ligand . ^^^ The level of IGF 1 receptor mRNA , however , was not altered by preincubating cells for up to 24 h with 6 . 5 nM IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study we provide support for the concept that heterogeneous IGF 1 receptors exist in the brain and that part of the heterogeneity is derived from IGF 1 receptor hybrids formed from different beta subunits . ^^^ The relationship of the two proteins to the IGF 1 receptor was further probed by an antibody ( a HF ) raised against a specific sequence in the beta subunit of the human IGF 1 receptor , and a polyclonal antibody raised against the liver insulin receptor ( L 1 ) which cross reacts with the IGF 1 receptor . ^^^ In conclusion , the brain IGF 1 receptor apparently has two structurally different beta subunits , one of 92 kDa and a second of 99 kDa . ^^^ Interestingly , at least a portion of the IGF 1 receptor population has both isoforms in the same receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) binding proteins and the IGF 1 receptor in rat kidney were studied to gain perspective on their potential roles in the control of renal cell mass . ^^^ IGF 1 affinity labeling studies demonstrated three proteins in both glomerular membranes and proximal tubule BLM ; molecular weight approximately 140 , 000 d , the alpha subunit of the IGF 1 receptor , a protein > 200 , 000 d , and a protein approximately 31 , 000 d that was immunostained with IGF binding protein 5 antibodies . ^^^ These studies suggest that cytosolic hypertrophy of proximal nephron structures is accompanied by membrane hypertrophy with a fixed density of IGF 1 receptor and IGF binding protein 5 . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis according to Scatchard revealed a decreased number of receptor sites on D NOD cells , although the structure of the IGF 1 receptor visualized by cross linking was identical for both cell types . ^^^
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These observations show that IGF 1 receptor mediates induction of specific proteins and suggest that these proteins may be involved in the neurotrophic activity of IGF 1 in the brain . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The function of the insulin receptor tyrosine kinase in signal transduction has been studied extensively in contrast to the IGF 1 receptor tyrosine kinase . ^^^ In the present study we have analyzed the regulatory function of the IGF 1 receptor tyrosine kinase and carboxyl terminal domains in mitogenic signaling by overexpression of mutant IGF 1 receptors in mouse NIH 3T3 fibroblasts . ^^^ A mutant IGF 1 receptor , in which 3 tyrosines ( Tyr 1131 , Tyr 1135 , and Tyr 1136 ) analogous to the three major autophosphorylation sites in the insulin receptor kinase were replaced by phenylalanines , was devoid of kinase activity in vivo and in vitro and inactive with respect to IGF 1 internalization and stimulation of thymidine incorporation . ^^^ Another mutant IGF 1 receptor , which lacks the 49 carboxyl terminal amino acids ( residues 1289 1337 ) of the beta subunit , was fully active . ^^^ Our data suggest that the structure function relationship of the IGF 1 receptor tyrosine kinase activation and signal transduction is similar to that of the insulin receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined rBP 1 effects on both IGF 1 binding to MCF 7 membranes and activation of type 1 IGF receptor ( IGFR 1 ) and found that 80 nM rBP 1 reduced IGF 1 receptor binding to levels of nonspecific binding and completely abolished ligand dependent IGFR 1 phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In previous studies , we have demonstrated that IGF 1 and IGF 1 receptor are expressed in rat uterus and that the expression is up regulated by estrogen . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor sub membrane domain is intact in GH secreting pituitary tumours . ^^^ We have previously shown that the 943 and 950 tyrosine residues in the IGF 1 receptor beta subunit are required for ligand signalling to the GH gene , as substitution of these residues abrogates IGF 1 signal transduction . ^^^ To determine whether a mutation within the IGF 1 receptor submembrane domain may be involved in the pathogenesis of GH secreting tumours , we studied this region in these tumours . ^^^ DESIGN : Exon 15 of the IGF 1 receptor containing both the 943 and 950 tyrosines was analysed in 19 GH secreting tumours by single strand conformation polymorphism ( SSCP ) analysis of polymerase chain reaction ( PCR ) products . ^^^ CONCLUSIONS : We conclude that mutations in the IGF 1 receptor sub membrane domain which disrupt the negative feedback loop are not involved in the pathogenesis of acromegaly . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , an mAb against the IGF 1 receptor , which has little direct effect on DiFi cell growth , can block the capacity of insulin / IGF 1 to delay apoptosis induced by mAb 225 , suggesting that the insulin / IGF 1 mediated delay of apoptosis is acting through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Specificity studies show insulin also binds the IGF 1 receptor with an affinity 20 fold lower than that of IGF 1 . ^^^ The 95 , 000 MW protein detected is equivalent to the molecular weight of the beta chain of the IGF 1 receptor described in other types of cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recent studies have indicated that both insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor mRNA are abundant in developing and adult olfactory bulbs , and that IGF 1 receptor mRNA is abundant in the prenatal cerebral cortex . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF IR ) is a heterotetramer composed of two cross linked extracellular alpha chains and two membrane spanning beta chains that contain a tyrosine kinase domain . ^^^ Several antibodies raised against linear epitopes within the CRR bound to solubilized and native rat and human IGF IR by ELISA , did not cross react with IR , but unexpectedly failed to inhibit 125I IGF 1 binding . ^^^ One of these , RAB 6 , directed against amino acids 38 44 of the IGF IR , inhibited 125I IGF 1 binding to rat aortic smooth muscle cells ( RASM ) and to IGF IR / 3T3 cells ( overexpressing human IGF IR ) by up to 45 % . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The treatment of wild type cells with antisense c myb or IGF 1 receptor oligonucleotides induces a late G 1 block in cell proliferation , which can be overcome by exposure to the calcium ionophore , 4 bromo A 27318 , in amounts sufficient to raise [ Ca2+ ] 1 to levels observed at the G1 / S interface . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , for all the effects measured in a cell free system , the chimeric receptor displayed an increased response to IGF 1 compared to the native IGF 1 receptor . ^^^ Conversely at 50 mM Mg2+ , the chimeric receptor behaved like the IGF 1 receptor , since the presence of Mn2+ decreased the stimulatory effect of IGF 1 on their kinase activity . ^^^ These data demonstrate that the replacement of the C terminal tail of the IGF 1 receptor by that of the insulin receptor has changed the receptor characteristics studied in a cell free system . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have investigated the mitogenic and transforming ability of an IGF 1 receptor with a 108 amino acid C terminal truncation in R cells , which are 3T3 like cells derived from mouse embryos in which the IGF 1 receptor genes have been disrupted by targeted homologous recombination . ^^^ R cells stably transfected with expression plasmids encoding either a wild type or a truncated human IGF 1 receptor were capable of growing in serum free medium supplemented solely with IGF 1 . ^^^ R cells overexpressing the wild type IGF 1 receptor also formed colonies in soft agar , and colony formation was augmented by coexpression of the SV 40 large T antigen . ^^^ However , all the examined clones of R cells expressing the truncated IGF 1 receptor exhibited a dramatically impaired ability to grow in soft agar , even in the presence of the T antigen . ^^^ The inability to form colonies in soft agar was not due to a quantitative impairment of signal transduction , because : ( 1 ) SV 40 transformed cells with a physiological level of the wild type IGF 1 receptor did not respond to IGF 1 with cell proliferation , but grew in soft agar ; ( 2 ) R cells stably transfected with both a truncated receptor and T antigen , on the contrary , responded with mitogenesis to IGF 1 but could not form colonies in soft agar ; ( 3 ) some clones with the truncated receptor expressed levels of receptor roughly 100 fold the level of wild type cells ; and ( 4 ) several parameters of IGF 1 receptor signal transduction were not impaired in cells stably transfected with a truncated receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We assessed the potential roles of insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor ( IGF IR ) in human pancreatic cancer . ^^^ IGF 1 enhanced the growth of ASPC 1 and COLO 357 human pancreatic cancer cells , and this effect was significantly inhibited by a highly specific monoclonal anti IGF IR antibody ( alpha IR 3 ) . ^^^ These findings suggest that IGF 1 may participate in aberrant autocrine and paracrine activation of IGF IR in pancreatic cancer in vivo . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To further evaluate the specific role of IGF 1 on luteal steroidogenesis , IGF 1 receptor was identified by chemical cross linking of [ 125I ] IGF 1 to mid CL membranes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of insulin was biphasic , suggesting some stimulation mediated directly by the insulin receptor and some by cross reaction with the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that measuring IGF 1 receptor levels using labeled IGF 1 may be misleading . ^^^ Estradiol caused a 2 . 5 fold increase in IGF 1 receptor levels . ^^^ This elevation in IGF 1 receptor levels and the decrease in IGFBP levels were accompanied by a 3 . 5 fold increase in IGF 1 receptor messenger RNA and a 2 . 5 fold decrease in IGFBP messenger RNAs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and IGF 2 receptor messenger RNAs ( mRNAs ) are both selectively concentrated in developing chondrocytes and osteoblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Nerve growth cones isolated from fetal rat brain are highly enriched in a 97 kDa glycoprotein , termed beta gc , that comigrates with the beta subunit of the IGF 1 receptor upon two dimensional PAGE and is disulfide linked to this receptor ' s alpha subunit . ^^^ Antibodies prepared to a conserved domain shared by the insulin and IGF 1 receptor beta subunits ( AbP 2 ) or to beta gc were used to study receptor distribution further . ^^^ Furthermore , the segregation of beta gc from AbP 2 immunoreactivity suggests that such neurons express an immunochemically distinct variant of the IGF 1 receptor beta subunit at the growth cone . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Clones MA5 / MA7 similarly showed a 54 % reduction in IGF IR number after confluence following exposure to 100 mumol / L ZnSO 4 and a 44 % and 58 % reduction in DNA synthesis , basally and in response to 10 ng / mL IGF 1 , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Suramin , like anti insulin like growth factor ( IGF ) or anti IGF 1 receptor antibodies , efficiently inhibits the growth of tumorigenic clones in defined medium . ^^^ These results indicate that autocrine growth stimulation of tumorigenic clones by IGFs through the IGF 1 receptor is essential for their ability to grow in defined medium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The priming of PMNLs by IGF 1 was dependent on time and concentration , and saturating amounts of a monoclonal antibody to the IGF 1 receptor blocked the priming of PMNLs by this peptide . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To study the role of the IGF 1 receptor in vascular smooth muscle cell growth , phosphorothioate oligonucleotides were used to modulate IGF 1 receptors . ^^^ Mismatch oligonucleotide had no effect , while surprisingly sense oligonucleotide increased IGF 1 receptor number and basal and serum induced DNA synthesis . ^^^ A 51 % reduction in IGF 1 receptor number following exposure to 5 microM antisense oligonucleotide markedly inhibited angiotensin 2 induced mitogenesis . ^^^ A 70 % increase in IGF 1 receptor number following exposure to 5 microM sense oligonucleotide resulted in a 4 fold increase in basal [ 3H ] thymidine incorporation , and angiotensin 2 ( 1 1000 nM ) had no additive stimulatory effect . ^^^ An antisense oligonucleotide targeting a sequence starting at +109 base pairs ( relative to ATG ) also reduced IGF 1 receptor number , however , the corresponding sense oligonucleotide was without effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : Insulin like growth factor 1 receptor ( IGF 1R ) and its ligand ( IGF 1 ) have been implicated in the growth of several cell types , including ventricular myocytes . ^^^ During early postnatal development , myocyte cell volume increases nearly 25 fold , and myocyte proliferation is markedly attenuated , so a progressive decrease in this signaling mechanism will indicate that the IGF 1 IGF 1R system is mostly involved in cell proliferation . ^^^ Conversely , a continuous increase in the expression of IGF 1 and IGF 1R in myocytes with maturation will suggest its involvement in cellular hypertrophy . ^^^ Total RNA was extracted from these cells , and the expression of IGF 1 , IGF 2 , IGF 1R , and DNA polymerase alpha was measured by reverse transcriptase PCR . ^^^ CONCLUSIONS : In conclusion , the decline in myocyte proliferation with cardiac development appears to be coupled with attenuation of the IGF 1 IGF 1R system , which may condition the changes in late growth regulated genes , DNA replication , and cellular mitotic division in the myocardium . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine if immunohistochemical detection of growth factors and / or their receptors correlates with morphological alterations in proliferative lesions of thyroid , we examined the localization of epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) and their common receptor , EGF receptor ( EGF R ) , insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor ( IGF R ) and IGF binding proteins ( IGFBP ) 1 , 2 , 3 , and 4 , nerve growth factor ( NGF ) , and its receptor NGF receptor ( NGF R ) , transforming growth factor beta ( TGF beta ) , and basic fibroblast growth factor ( bFGF ) , in normal thyroid tissue and various thyroid tumors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To understand the mechanism of activation of IGF 1 dependent PTK by DES , we investigated the relationship between the binding capacity of IGF 1 to membrane proteins and the level of IGF IR . ^^^ These findings suggest that an enhanced level of IGF IR coupled with qualitative changes may be responsible for the activation of IGF 1 dependent PTK on DES exposure . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
R cells are 3T3 like cells derived from mouse embryos in which the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) genes have been disrupted by targeted homologous recombination . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The distribution of IGF 1 receptor is reported in the odontogenic epithelium and mesenchyme of the continuously erupting mandibular incisor of the rat by immunohistochemistry using a polyclonal antibody specific to the IGF 1 receptor . ^^^ The distribution and intensity of IGF 1 receptor expression varied with the phenotypic stages of the ameloblasts . ^^^ Diffuse cellular staining for IGF 1 receptor was found during the active secretory phase of amelogenesis . ^^^ This transition is accompanied by programmed cell death ( apoptosis ) of approximately 25 % of the ameloblasts and cells in this zone did not stain for IGF 1 receptor . ^^^ Strong IGF 1 receptor immunoreactivity was observed in the stratum basale and stratum spinosum of the adjacent labial gingival epithelium . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Therefore , we evaluated 29 human sarcoma specimens for expression of IGF 1 receptor , IGF 1 , and IGF 2 by competitive binding and reverse transcription polymerase chain reaction ( RT PCR ) techniques . ^^^ Twelve of 29 sarcomas examined by RT PCR and 13 of 25 examined by affinity binding studies expressed IGF 1 receptor levels equal to or greater than levels determined in the IGF responsive MCF 7 breast carcinoma cell line . ^^^ DNA amplification of the IGF 1 receptor gene was not identified in this group of sarcomas that expressed high levels of IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that insulin and IGF 1 potentiate the glibenclamide sensitive K+ current by activating IGF 1 receptor and that pertussis toxin sensitive G protein may be associated with these effects . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The exact nature of how the insulin molecule interacts with the insulin receptor is obscure although chimeric receptors have shown that the ligand specificity of the insulin receptor and the IGF 1 receptor ( i . e . the sequences that discriminate between insulin and insulin like growth factor 1 ) reside in different regions of a common binding site and that the N terminal 68 amino acids of the insulin receptor are involved in conferring specificity for insulin on this receptor ( Kjeldsen , T . , Andersen , A . ^^^ Furthermore , replacement of the insulin receptor amino acid phenylalanine 39 with the corresponding IGF 1 receptor amino acid , serine 35 , decreased insulin affinity 8 fold . . ^^^ Using chimeric insulin / IGF 1 receptors to elucidate how the insulin receptor interacts with the insulin molecule we identified phenylalanine 39 of the insulin receptor as a major contributor in determining the receptor specificity for insulin , increasing insulin affinity 15 fold when replacing the corresponding amino acid in the insulin like growth factor 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we have measured the mRNA levels of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor ( IGF IR ) , alkaline phosphatase , and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS 54 and compared the results with those obtained from their ground based controls and from the bones of hindlimb elevated animals . ^^^ Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF 1 , IGF IR , and alkaline phosphatase but decrease the mRNA levels for osteocalcin . ^^^ The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation , whereas the rise in IGF 1 and IGF IR mRNA levels may indicate a compensatory response to the fall in bone formation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor prevent etoposide induced apoptosis . ^^^ The interaction of insulin like growth factors ( IGF ) with the IGF 1 receptor promotes cell proliferation and survival . ^^^ We examined the role of the IGF 1 receptor as a possible direct inhibitor of apoptosis induced by the topoisomerase 1 inhibitor etoposide . ^^^ When exposed to this agent , BALB / c 3T3 cells that constitutively overexpress the human IGF 1 receptor ( p 6 cells ) arrested in S phase and subsequently underwent apoptosis as determined by the appearance of a pre G 1 apoptotic peak when studied by flow cytometry and the characteristic internucleosomal fragmentation of DNA . ^^^ IGF 1 was less effective in preventing apoptosis in parental BALB / c 3T3 cells and had no effect on etoposide induced cell killing of mouse embryo fibroblasts that have a targeted disruption of the IGF 1 receptor gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that the activated IGF 1 receptor does not use pertussis toxin sensitive G proteins or diacylglycerol generation in a pathway leading to DNA synthesis in MG 63 cells . . ^^^ We have examined the roles of pertussis toxin sensitive G proteins and diacylglycerol generation in signaling by the insulin like growth factor 1 receptor in a cell line that is very responsive to IGF 1 , the human osteosarcoma cell line , MG 63 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Down regulation of the IGF 1 receptor by pre incubation with IGF 1 was demonstrated for syncytiotrophoblasts with a maximum decrease in IGF 1 binding of 67 per cent after 72 h pre incubation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , using wild type HTC cells , we investigated whether the activated IGF 1 receptor also forms a similar signaling complex . ^^^ To study the proteins present in IGF 1 receptor signaling complexes , we used immunoprecipitation and Western blotting analysis with appropriate antibodies . ^^^ These studies suggest , therefore , that the IGF 1 receptor , like the insulin receptor , induces the formation of multiple signaling complexes that most likely mediate the proliferative effects of these receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To identify domains in the IGF 1 receptor that are necessary for transformation , the tyrosine at residue 950 of the human IGF 1 receptor cDNA was mutated to phenylalanine , and the plasmid expressing the mutant receptor was stably transfected into R cells , which are mouse embryo fibroblasts with a targeted disruption of the type 1 receptor for the insulin like growth factors . ^^^ These experiments show , for the first time , that tyrosine 950 of the IGF 1 receptor is necessary for its mitogenic and transforming activities . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) stimulates the production of 3 phosphoinositides and increases the phosphatidylinositol 3 kinase activity that is immunoprecipitated by antiphosphotyrosine antibodies , a small portion of which are also associated with the IGF 1 receptor . ^^^ In vitro reconstitution experiments showed that p 85 associates with high affinity to the IGF 1 receptor and this interaction is mediated through the p 85 SH2 groups . ^^^ Moreover , in vitro , p 85 is a substrate for the IGF 1 receptor tyrosine kinase activity . ^^^ Only a small fraction of p 85 was associated with the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In a human breast cancer cell line MCF 7 , which expresses IGF 1 receptor ( IGF IR ) , stimulation with insulin or IGFs resulted in autophosphorylation of the IGF IR in an increased proportion of ras bound to GTP and in the association of phosphatidylinositol 3 ' kinase ( PI3K ) activity and of p 85 PI3K with M ( r ) 185 , 000 phosphotyrosinylated proteins corresponding in size to insulin / IGF IR substrates . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of insulin like growth factor ( IGF ) 2 and IGF 1 receptor during proliferation and differentiation of CaCo 2 human colon carcinoma cells . ^^^ Reduced IGF 2 expression was associated with a decrease in IGF 1 receptor number that was high in proliferating cells ( approximately 80 , 000 binding sites / cell ) and reduced by 4 fold in differentiated cells . ^^^ IGF 2 acted through the IGF 1 receptor , since both basal and IGF 2 stimulated cell proliferation was inhibited by the monoclonal antibody alpha IR 3 , which blocks the binding sites of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Prognostic value of IGF 1 receptors ( IGF 1R ) was evaluated and compared with circulating prolactin ( PRL ) in 59 patients with Dukes B or C colon / rectal cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mutation of a conserved amino acid residue ( tryptophan 1173 ) in the tyrosine kinase domain of the IGF 1 receptor abolishes autophosphorylation but does not eliminate biologic function . ^^^ To study the importance of this residue in IGF 1 receptor function , we mutated the analogous tryptophan residue at position 1173 of the IGF 1 receptor to serine and overexpressed the mutant receptor in NIH 3T3 cells . ^^^ In cell lines overexpressing this mutant IGF 1 receptor , beta subunit autophosphorylation was severely reduced . ^^^ Wheat germ agglutinin purified mutant receptors were as active in phosphorylating poly ( Glu , Tyr ) 4 : 1 as wild type IGF 1 receptors , suggesting that , in intact cells , additional factors are necessary in order for the IGF 1 receptor to phosphorylate IRS 1 . ^^^ Thymidine incorporation was severely reduced in one clone overexpressing the mutant IGF 1 receptor and abolished in a second clone . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here the role of IGF 1 and its receptor ( IGF 1R ) in metastasis was further investigated using H 59 cells transfected with a plasmid vector expressing IGF 1R cDNA in the antisense orientation . ^^^ The transfectants had a markedly reduced expression of IGF 1R and lost the ability to respond to IGF 1 in vitro . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor immunoreactivity showed a similar pattern to that for 125I IGF 1 binding , with immunoreactivity being found in the gray matter of the spinal cord and enhanced immunoreactivity occuring in ALS patients compared to controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin / insulin like growth factor 1 ( IGF 1 ) hybrid receptors are composed of an alpha beta heterodimer from an insulin receptor and an alpha beta heterodimer from an IGF 1 receptor . ^^^ The IGF 1 receptor in rodent fibroblasts has two receptor isoforms , one with a 95 kilodalton ( kDa ) beta subunit and one with an 105 kDa beta subunit . ^^^ The kinase defective insulin receptor heterodimer functions as a dominant negative , inhibiting phosphorylation by the kinase competent IGF 1 receptor heterodimer . ^^^ Despite an increasing percentage of insulin / IGF 1 hybrid receptors in the three cell lines studied , the rates of IGF 1 internalization and degradation remain similar to those mediated by the IGF 1 receptor and distinct from those of insulin receptor heterotetramers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using R cells , i . e . , mouse embryo cells in which the IGF 1 receptor genes have been disrupted by homologous recombination , we show here that the functional integrity of the IGF 1 receptor is obligatory for the PDGF induced increase in PCNA mRNA levels . ^^^ However , PCNA pre mRNA levels are increased by PDGF even in the absence of the IGF 1 receptor . ^^^ These experiments confirm the importance of the IGF 1 receptor in the control of cellular proliferation in animal cells , and suggest that one of its functions may be in the processing of certain pre mRNAs required for orderly cell cycle progression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF 1R ) are required for cell proliferation in vitro , raising the possibility that an autocrine IGF 1 IGF 1R system may be present in vivo and become activated in the viable ventricular myocytes shortly after infarction . ^^^ Therefore , following the in vivo documentation of left ventricular failure in rats subjected to occlusion of the left coronary artery , the unaffected myocytes of the left ventricle were enzymatically dissociated and the expression of IGF 1R and IGF 1 mRNAs were measured at 12 h and at 1 , 2 3 , and 7 days after surgery . ^^^ Thus , the IGF 1R IGF 1 autocrine system may modulate myocyte cellular hyperplasia in the failing heart . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In PCO ovaries associated with hyperinsulinemia , no expression of insulin receptors was detected in granulosa or thecal stromal cells , while IGF 1 receptor expression increased in thecal stromal cells but decreased in granulosa cells compared to those in normal ovaries . ^^^ However , in PCO ovaries from patients without hyperinsulinemia , insulin receptor expression was apparent in both granulosa and thecal stromal cells , with a similar intensity to that observed in normal ovaries , while IGF 1 receptor expression was negligible in granulosa cells but sustained in thecal stromal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In vivo treatment with antibody against IGF 1 receptor suppresses growth of human rhabdomyosarcoma and down regulates p34cdc2 . ^^^ In addition , we demonstrated that the inhibition of binding of IGF 2 to the IGF 1 receptor , mediated by suramin , blocked the growth of RMS cells in vitro . ^^^ We now report that , in vivo , a specific IGF 1 receptor blocking antibody ( alpha IR 3 ) , but not suramin , suppresses RMS tumor growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor autophosphorylation was also markedly reduced in 15 day and 22 day old lurcher cerebella . ^^^ These results suggest that the process of cerebellar degeneration in human OPCA and lurcher mutant mouse may be associated with altered IGF 1 receptor binding and protein tyrosine phosphorylation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The monoclonal antibody alpha IR 3 , which binds to the alpha subunits of the IGF 1 receptor , was used for specific binding and the peroxidase antiperoxidase method was used for staining . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , IGF 1 bound to the partially purified IGF 1 receptor with an apparent affinity ( ED 50 = 3 . 7 nM ) that was similar to the concentrations of IGF 1 which caused half maximal activation of 3 O methylglucose uptake ( ED 50 = 2 . 4 nM ) and GLUT 4 translocation ( ED 50 = 2 . 5 nM ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) is a useful therapeutic agent in insulin resistant diabetes mellitus due to insulin receptor disease because of its hypoglycaemic effects through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF II / mannose 6 phosphate receptor was purified from rat placental membranes , the IGF 1 receptor was solubilized from human placental membranes and IGF binding proteins were partially purified from adult and three day old rat sera by sequential gel filtration on Sephadex G 200 ( pH 8 . 0 ) and Sephadex G 50 ( acid pH ) . ^^^ The dose / response curves of the two IGF 2 species were indistinguishable in radioreceptor assays utilizing the IGF II / mannose 6 phosphate receptor and the IGF 1 receptor and in IGF competitive binding assays utilizing partially purified IGF binding proteins . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is the major substrate of insulin receptor and IGF 1 receptor tyrosine kinases ; it has an apparent relative molecular mass of 160 190 , 000 ( M ( r ) , 160 190K ) on SDS polyacrylamide gel . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Radioreceptor cross linking indicated that IGF 2 interacted principally with the IGF 1 receptor , although low levels of the IGF II / mannose 6 phosphate receptor were also expressed on the cell surface . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 IGF 1 receptor system modulates myocyte proliferation but not myocyte cellular hypertrophy in vitro . ^^^ Therefore , to determine the role of IGF 1 receptors on myocyte growth , cells were exposed to antisense oligodeoxynucleotides to IGF 1 receptor mRNA and the effects of this intervention on DNA synthesis , nuclear mitotic division , and changes in the number of myocytes were measured . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Bioactivity must be similar to that of insulin without any enhancement of mitogenic properties due to an increase of the affinity for IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reintroduction into these cells ( null for the IGF 1 receptor ) of a wild type ( but not of a mutant ) IGF 1 receptor restores EGF mediated growth and transformation . ^^^ Our results indicate that at least in mouse embryo fibroblasts , the EGFR requires the presence of a functional IGF 1 receptor for its mitogenic and transforming activities . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
While hCG had no effect on EGF receptor binding parameters , it increased the Ka of the IGF 1 receptor and enhanced the effect of E 2 on IGF 1 receptor number . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An insulin like growth factor 2 ( IGF 2 ) analog with highly selective affinity for IGF 2 receptors stimulates differentiation , but not IGF 1 receptor down regulation in muscle cells . ^^^ IGF 2 , the principal IGF peptide expressed by differentiating muscle cells , has been implicated in at least two autocrine / paracrine actions in this tissue : stimulation of differentiation and down regulation of the IGF 1 receptor . ^^^ IGF 1 receptor down regulation was assessed by receptor binding and mRNA abundance . ^^^ In IGF 1 receptor down regulation studies , IGF 2 pretreatment significantly decreased binding of IGF 1 to the IGF 1 receptor and decreased IGF 1 receptor mRNA , whereas the IGF 2 analog had only minimal effects . ^^^ Thus , in addition to the IGF 1 receptor which has been previously found to signal IGF induced myogenesis , these results implicate a role for the IGF 2 receptor in this process . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present work , we report that while the IGF 1 receptor exhibits negative cooperativity like the insulin receptor , the concentration dependence of the dissociation kinetics is distinct from that of native human insulin by not being bell shaped , but monophasic like that of insulin analogues mutated at the hexamer forming surface ; it is changed to an insulin type curve by substitution of IGF 1 receptor ' s sequence including residues 382 565 with the homologous insulin receptor domain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Undifferentiated cells around fat cell clusters were reactive for the IGF 1 receptor , but fat cells showed no reactivity . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mechanisms of insulin like growth factor ( IGF ) 2 induced IGF 1 receptor down regulation in BC3H 1 muscle cells . ^^^ We have previously demonstrated that treatment of myoblasts with IGF 2 decreased IGF 1 receptor biosynthesis and steady state mRNA levels . ^^^ In addition , muscle cell differentiation was associated with a marked increase in the expression and secretion of IGF 2 followed by similar down regulation of the IGF 1 receptor , suggesting an autocrine role for IGF 2 in this process . ^^^ To explore further the mechanisms by which IGF 2 decreases IGF 1 receptor expression in BC3H 1 muscle cells , dose response studies of IGF 1 and 2 treatment on the amount of IGF 1 receptor mRNA were carried out . ^^^ In addition , to determine whether IGF 2 decreases IGF 1 receptor expression by stimulating receptor protein degradation , pulse / chase experiments with [ 35S ] methionine / cysteine were carried out . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Stimulation of insulin receptors alone , with 2 . 5 pg / mL insulin receptor specific antibody , stimulates glucose transport by 20 % , suggesting transport can be stimulated by an IGF 1 receptor independent mechanism . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate this phenomenon , we studied the IGF 1 responsiveness of human marrow cells expressing IGF 1 receptor ( IGF IR ) , a direct strategy not used previously . ^^^ Accordingly , if IGF 1 plays a role in hematopoietic colony formation , it is probably and results from stimulation of IGF IR positive ancillary cells to secrete growth factors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Northern blot hybridization using a rat type 1 IGF 1 receptor gene riboprobe showed that although dexamethasone alone did not increase IGF 1 receptor mRNA concentrations , it did prevent a decrease in receptor mRNA concentrations caused by IGF 1 . ^^^ In addition , we used synthetic primers from conserved regions of the rat type 1 IGF 1 receptor gene with total RNA from porcine granulosa cells and polymerase chain reaction to isolate a 615 base pair porcine type 1 IGF 1 receptor cDNA clone . ^^^ Ribonuclease protection assay results were similar to those found with the rat IGF 1 receptor riboprobe . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity cross linking of cell membranes using disuccinimidyl suberate as a cross linking agent under reducing conditions revealed a single polypeptide band ( relative mol wt 133 , 000 ) representing the alpha subunit of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To define domains that might contribute to differences between IGF 1 and insulin receptors , we cloned the rat IGF 1 receptor cDNA and performed a comparative sequence analysis of specific functional domains in the two receptor types of rats and humans . ^^^ In the region corresponding to the CAG+ / alternative splicing site of the human IGF 1 receptor , a nucleotide change in the rat eliminates the alternative acceptor splice site . ^^^ The rat IGF 1 receptor has no equivalent to the alternatively spliced exon 11 of the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PURPOSE : To clarify the specific signalling pathway of IGF 1 , we studied the functional role of heterodimers composed of IGF 1 receptor and insulin receptor for the IGF 1 signalling . ^^^ Heterodimers between rat IGF 1 receptor and exogenous insulin receptors were identified by a human specific anti insulin receptor monoclonal antibody after ligand affinity labeling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To further define the IGF 1 postreceptor events occurring in GH secreting cells , we investigated the activity of ERKs in response to IGF 1 in GC cells following stable transfection with either wild type human IGF 1 receptor cDNA ( WT cells ) or a mutant cDNA encoding a truncated , kinase defective IGF 1 receptor with a dominant negative effect on endogenous receptor function ( 952STOP cells ) . ^^^ In contrast , 12 O tetradecanoylphorbol 13 acetate stimulated ERK activity to the same degree in all three cell types regardless of their IGF 1 receptor status . ^^^ The rapid , dose dependent , and IGF 1 receptor dependent activation of ERKs and the attenuation of this effect by cAMP suggest an interrelated role for both molecules in IGF 1 signal transduction in GH secreting cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Virtually all members of the GH / IGF axis are present in the kidney , comprising : 1 ) GH receptors ; 2 ) IGF 1 and IGF 2 mRNA ; 3 ) distinct receptors for IGFs : the IGF 1 receptor and the IGF 2 / mannose 6 phosphate receptor , and 4 ) specific binding proteins ( IGFBPs ) , indicating that GH and IGFs may affect the kidney in both an endocrine and autocrine / paracrine fashion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The growth of human melanoma cells FO 1 in nude mice is strongly inhibited or even abrogated when the cells are stably transfected with a plasmid expressing an antisense RNA to the insulin like growth factor 1 receptor ( IGF 1R ) RNA , which causes a marked reduction in the number of IGF 1 receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Preincubation of bovine fibroblasts with concentrations of insulin that did not bind to the IGF 1 receptor resulted in complete but reversible cellular desensitization to IGF 1 stimulated mitogenesis . ^^^ Neither serum stimulated mitogenesis nor IGF 1 stimulated glucose uptake were affected by insulin pretreatment . 125I labeled IGF 1 affinity cross linking experiments indicated that preincubation with insulin did not affect labeling of the 130 , 000 M ( r ) alpha subunit of the IGF 1 receptor , but was associated with the loss of IGF 1 and insulin inhibitive bands at M ( r ) = 100 , 000 , 85 , 000 , 58 , 000 , and 34 , 000 . ^^^ These studies suggest that insulin , via interaction with insulin receptors on bovine fibroblasts , regulates IGF 1 action at a step distal to IGF 1 receptor binding and are consistent with desensitization occurring at an intracellular step in the mitogenic pathway shared by insulin and IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Interestingly , this alternative splicing occurs at a position at which alternative splicing of the homologous IGF 1 receptor mRNA also occurs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since the effective dose of insulin ( 0 . 5 microgram / ml or higher ) is much higher than the physiological concentration , the effects of insulin may be via IGF 1 receptor . ^^^ These data suggest that insulin , probably via IGF 1 receptor , attenuates [ Ca2+ ] 1 responses and cell contraction of mesangial cells induced by vasoactive agents . ^^^ The modification of mesangial cell function through IGF 1 receptor may play a role in the regulation of glomerular hemodynamics . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine whether the capacity to produce and respond to these growth factors changes during skeletal development , we measured the protein and mRNA levels for IGF 1 , IGF 2 , and their receptors ( IGF IR and IGF IIR , respectively ) in the tibia and femur of rats before and up to 28 mo after birth . ^^^ However , after 6 wk , both IGF 1 and IGF IR mRNA levels recovered toward the levels observed at birth . ^^^ In the prenatal bones , the signals for the mRNAs of IGF 2 and IGF IIR were stronger than the signals for the mRNAs of IGF 1 and IGF IR , although the content of IGF 1 was three to fivefold greater than that of IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In dominant follicles , no IGF 1 mRNA was seen in either thecal or granulosa cells ( GC ) , but IGF Ir mRNA was expressed in GC . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To stimulate growth , therapy with rhGH was initiated , the rationale being to stimulate hepatic IGF 1 production and IGF 1 receptor signaling , and bypass the inherited block in insulin receptor signaling . ^^^ The lack of efficacy of IGF 1 treatment may be related to multiple factors , such as the poor metabolic state of the patient , the deficiency of serum carrier protein for IGF 1 , an increased clearance of the growth factor , IGF 1 resistance in target cells at a receptor or postreceptor level , or an inhibitory action of the mutant insulin receptors on IGF 1 receptor signaling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To assess directly the role of the IGF 1 receptor in rhabdomyosarcoma cell growth and tumorigenicity , a human alveolar rhabdomyosarcoma cell line with high IGF 1 receptor expression was transfected with an amplifiable IGF 1 receptor antisense expression vector . ^^^ Four unique , transfected clones were analyzed and found to have reduced IGF 1 receptor expression relative to the parental line . ^^^ Reduced IGF 1 receptor surface expression in the transfectants was shown by decreased immunofluorescence with an IGF 1 receptor monoclonal antibody and by decreased IGF 1 binding as measured by Scatchard analysis . ^^^ These results demonstrate that reduction of IGF 1 receptor expression can inhibit both the in vitro and in vivo growth of a human rhabdomyosarcoma cell line and suggest a role for the IGF 1 receptor in mediating neoplastic growth in this mesenchymally derived tumor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor densities in white matter were significantly higher in neonates than in adults ; during adult life there was no further decline . ^^^ There was no significant decrease in IGF 1 receptor densities in the cortical mantle with age , suggesting that the cells containing IGF 1 receptors in frontal cortex are maintained during the entire life span . ^^^ There were no significant alterations in IGF 1 receptor densities in frontal cortex and white matter from patients with Huntington ' s disease and Alzheimer ' s disease compared with controls from the same age groups . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , in a subset of experiments acid prewashes with acetate also decreased binding of [ 125I ] IGF 1 to the IGF 1 receptor by 20 % . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor , which binds IGF 1 with the highest affinity and which is very similar to the insulin receptor , is thought to mediate most , if not all , of the IGF induced biological functions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IRS 1 has a central role as an adaptor molecule that links the insulin receptor and IGF 1 receptor kinases with enzymes that regulate cellular metabolism and growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By using cells overexpressing the IGF 1 receptor , and cells with a targeted disruption of the IGF 1 receptor genes , we show that : 1 ) the activation of the IGP 1 receptor by its ligand ( s ) plays a major role in the ability of the SV 40 large T antigen to promote growth in low serum ; and 2 ) the IGF 1 receptor plays a role in the progression of cells not only through G 1 , but also through the S and G 2 phases of the cell cycle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since muscle IGF 1 receptor gene expression did not decrease in parallel with receptor number , an alteration in IGF 1 receptor messenger RNA ( mRNA ) translation or receptor degradation may be hypothetized . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , enhancement by GH was not mediated by IGF 1 , because enhancement was blocked by anti GH antibody ( Ab ) , but not by Ab to IGF 1 or IGF 1 receptor . ^^^ Conversely , the enhancement by IGF 1 was blocked by either Ab to IGF 1 or IGF 1 receptor , but not by anti GH Ab . ^^^ Again , enhancement by GH was specifically blocked by anti GH Ab , whereas enhancement by IGF 1 was specifically blocked by either Ab to IGF 1 or IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RA mediated inhibition of IGF 1 stimulated growth is not associated with either a decrease in IGF 1 receptor number or affinity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the 4 5 week placentas , IGF 1 and IGF 1 receptor were almost exclusively localized in cytotrophoblasts and IGF 1 augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL . ^^^ By contrast , in the 6 12 week placentas , IGF 1 and IGF 1 receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF 1 stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of cytotrophoblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although mouse preimplantation embryos express transcripts for the insulin like growth factor 1 receptor ( IGF IR ) , IGF 1 transcripts were not detected by reverse transcription PCR ( RT PCR ) at any stage of preimplantation development in a previous study ( Rappolee et al . , Genes Dev 6 : 939 952 , 1992 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The half maximal concentration for migration is similar to the Kd for IGF 1 receptor interaction . ^^^ An IGF 1 receptor blocking antibody blocks the effects of IGF 1 , IGF 2 , and insulin , indicating that the effects are indeed mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In situ hybridization was used to investigate the cellular distribution of IDE mRNA and to compare it with insulin receptor ( IR ) and IGF 1 receptor ( IGFR ) gene expression in serial thin sections from a variety of tissues in embryonic and adult rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We therefore transfected wild type and truncated beta subunit mutant ( 952STOP ) human IGF 1 receptor cDNAs into Rat 1 fibroblasts . ^^^ Rat 1 transfectants expressed 2 . 5 to 7 fold increased IGF 1 receptor mass , while the Kd for IGF 1 binding was unchanged . ^^^ Therefore , 952STOP behaves as a dominant negative inhibitor of endogenous IGF 1 receptor function , probably by assembling nonfunctional hybrid rat / mutant human receptor tetramers . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that IGF 1 and its homologues are potent stimulators of phagocytosis and that this action is modulated by IGFBP , and may require extracellular Ca2+ and / or IGF 1 receptor G protein coupling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) , IGF 2 , and the type 1 IGF receptor ( IGF IR ) gene transcripts were localized in sections of ovine uterus collected from 53 ewes at different stages during the estrous cycle and the first 3 weeks of pregnancy using in situ hybridization with synthetic oligonucleotides . ^^^ Binding studies on cryostat sections using [ 125I ] IGF 1 or [ 125I ] des ( 1 3 ) IGF 1 were carried out to assess whether binding sites for IGF 1 colocalized with sites of IGF IR gene transcription . ^^^ Transcription in the deep glands remained high throughout the cycle , but in the superficial glands and myometrium , a small peak occurred in the early luteal phase ( days 1 2 ) , 24 48 h after peak IGF 1 gene transcription . [ 125I ] IGF 1 and des ( 1 3 ) IGF 1 binding sites colocalized with sites of IGF IR gene transcription . ^^^ Comparisons between pregnant and nonpregnant ewes on days 2 15 after estrus did not reveal any clear pregnancy associated differences in either the sites or levels of IGF 1 , IGF 2 , or IGF IR gene transcription . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The interaction of insulin like growth factors ( IGFs ) with the IGF 1 receptor is an important step in the control of cell proliferation and development . ^^^ Treatment of growth arrested cells with PDGF or temperature shift was accompanied by a transient increase in the expression of the mRNA for the IGF 1 receptor . ^^^ Transfection with a plasmid constitutively expressing the full cDNA for the human IGF 1 receptor allowed autonomous growth in serum free medium at 34 degrees C . ^^^ By contrast , growth induction by growth factors or temperature shift was abrogated by transfection of the cells with a plasmid expressing a 300 bp segment of mRNA antisense to the IGF 1 receptor mRNA . ^^^ Cloning in soft agar was also inhibited by expression of antisense IGF 1 receptor mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We show here that PDGF also increases the levels of IGF 1 receptor mRNA . ^^^ Using cell lines stably transfected with an expression plasmid in which the reporter luciferase gene is under the control of the rat IGF 1 receptor gene promoter , we find that PDGF increases the activity of this promoter . ^^^ A short IGF 1 receptor gene promoter , comprising about 100 base pairs of the sequence immediately upstream of the initiation of transcription site , is sufficient for a response to the stimulatory action of PDGF . ^^^ These results suggest that an increase in RNA levels and in promoter activity may play an important role in the increase in IGF 1 receptor levels that occurs after stimulation by PDGF . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Northern analysis for RNAs of the insulin like growth factor ( IGF ) regulatory system indicates that RNAs for IGF 1 , IGF 1 receptor , and IGF binding proteins ( IGFBP ) 2 6 , but not IGFBP 1 , are expressed in MDG2 . 1 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Alanine substitution for the positively charged residues in the C and D regions of IGF 1 led to 15 and 10 fold losses , respectively , in binding potency for the human IGF 1R , but they increased the potency of binding to the human IR 29 and 6 fold , respectively . ^^^ These data suggest that the positive charges in the C and D regions of IGF 1 contribute significantly to the binding preference of the IGF 1R for IGF 1 . ^^^ In complementary experiments using chimeric receptors we have also shown that the IGF 1 receptor elements required to discriminate in favor of the positive charges in the C and D regions are contained in the N terminal 283 amino acids of the alpha subunit . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Iodine 125 labeled IGF 1 ( [ 125I ] IGF 1 ) binding was characteristic of the IGF 1 receptor , and binding kinetics as well as receptor densities were similar in cortical and medullary membranes . ^^^ Affinity cross linking experiments displayed a band at an apparent molecular weight of 135 kD , corresponding to the size of the alpha subunit of the IGF 1 receptor . ^^^ In both regions of the bovine adrenal gland the IGF II / M6P receptor is much more abundant than the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Comparison of insulin and IGF 1 effects on IR and IGF 1R cells , respectively , indicated that the IR is more efficient in stimulating glycogen synthesis and p44mapk activity than is the IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , each amino acid appears to independently contribute to the overall ligand stimulated IGF 1 receptor internalization rate . ^^^ The effect of receptor occupancy on IGF 1 receptor endocytosis was also tested . ^^^ The rate of 125I labeled IGF 1 internalization by transfectants overexpressing the wild type IGF 1 receptor was rapid but decreased markedly in the presence of increasing unlabeled IGF 1 ( ED 50 = 44 , 000 receptors / cell ) . ^^^ These results suggest that ligand mediated internalization of the human IGF 1 is consistent with saturable interactions between the IGF 1 receptor juxtamembrane region ( glycine 940 tyrosine 957 ) and components of the endocytic apparatus . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunofluorescence microscopy was carried out on twelve meningotheliomatous meningiomas using antibodies directed against insulin , IGF 1 , IGF 2 , insulin receptor and IGF 1 receptor . ^^^ In addition , the IGF 1 receptor was expressed in four of the tumors while the insulin receptor was expressed in 10 out of 12 meningiomas . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These data demonstrate that human osteogenic sarcoma cell lines are dependent on signaling through the IGF 1 receptor for in vitro survival and proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both antisense IGF 1R oligodeoxynucleotides and stable transfection with a plasmid expressing an antisense IGF 1R RNA inhibited IGF 1 mediated growth in monolayers and clonogenicity in soft agar . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The intraassay variation was 9 % ( n = 22 ) for the IGF 1 receptor concentration and 12 % ( n = 22 ) for the insulin receptor . ^^^ The interassay variation was 5 % ( n = 4 ) for the IGF 1 receptor and 10 % ( n = 4 ) for the insulin receptor . ^^^ The coefficient of variation of the dissociation constants ( Kd ) was 26 % ( n = 7 ) for the IGF 1 receptor and 24 % ( n = 7 ) for the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we purified the CT domain of 98 amino acids from bacterial cells over expressing the CT domain and examined its effect on insulin and IGF 1 receptor protein kinases . ^^^ The purified CT domain stimulated the kinase activities of purified insulin receptor transmembrane / cytoplasmic domain ( IRTMTPK ) and its CT domain deletion mutant ( IRTMTPK delta CT ) , 3 . 3 fold and 2 . 3 fold , respectively , while it was less effective in stimulating the kinase activity of purified IGF 1 receptor transmembrane / cytoplasmic domain ( IGFIRTMTPK ) ( 1 . 4 fold ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We believe that several medium components contribute to the suppression of IGF 2 expression in myoblasts incubated in high serum `` growth ' ' medium , and conclude that the IGF 1 receptor mediates the feedback inhibition of IGF 2 gene expression in muscle cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor gene expression , however , describes an apparently identical pattern in the tissues of both rat and human , suggesting that , although local sources and presumably regulation of IGF expression vary between the species , the ultimate functions served might be the same . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thirteen tissue specimens from primary ovarian cancers , 1 specimen from a primary peritoneal carcinoma , 10 specimens from metastatic lesions of ovarian carcinomas , and 4 specimens from recurrent ovarian cancers together with 13 normal ovaries were tested for their content of insulin and IGF 1 receptors , by the application of specific insulin and IGF 1 receptor radioimmunoassays . ^^^ The insulin receptor ( IR ) and IGF 1 receptor ( IGF R ) content in the primary tumors varied between 23 . 8 321 . 4 and 16 . 4 554 . 2 ng / 0 . 1 mg DNA , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
At an IGF 1 concentration of 1 ng / ml , this response appeared specific for the IGF 1 receptor and was sensitive to pretreatment with pertussis toxin , thus implicating a role for a G protein . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Human osteosarcoma ( U 2 OS ) cells express both insulin like growth factor 1 ( IGF 1 ) receptors and insulin like growth factor II / mannose 6 phosphate ( IGF II / M6P ) receptors and synthesize IGF 2 : autocrine growth stimulation by IGF 2 via the IGF 1 receptor . ^^^ In addition , in Northern blotting experiments using total RNA from U 2 OS cells IGF 1 receptor RNA of 11 kb and IGF II / M6P receptor RNA of approximately 9 kb were detected . ^^^ Solution hybridization experiments confirmed the presence of IGF 1 receptor and IGF II / M6P receptor RNA . ^^^ The anti IGF 1 receptor antibody alpha IR 3 blocked the IGF 1 and IGF 2 stimulated increase of 3H thymidine uptake . ^^^ In addition , basal DNA synthesis was partially inhibited by the anti IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have localized and quantified in situ IGF 1 receptor expression in intact articular cartilage of normal mice . ^^^ The IGF 1 receptor was detected immunohistochemically with antibodies to the IGF 1 receptor and visualized with conventional light microscopy and confocal laser scanning microscopy ( CLSM ) . ^^^ CLSM analysis enabled us to distinguish IGF 1 receptor immunoreactivity on the chondrocyte cell membrane from intracellular staining . ^^^ We have established two approaches to quantify in confocal images low levels of fluorescence intensity of the immunolocalized IGF 1 receptor at the chondrocyte membrane , i . e . , mean pixel measurement and area measurement . ^^^ The majority of IGF 1 receptor fluorescence intensity was localized on chondrocytes in the middle and deeper zones of cartilage , whereas chondrocytes in the surface zone exhibited negligible fluorescence . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The function of insulin receptor and IGF 1 receptor was investigated in placentas from 10 healthy control mothers , 8 diabetic mothers with appropriate for gestational age babies ( AGA group ) and 9 diabetic mothers with large for gestational age babies ( LGA group ) . ^^^ Autophosphorylation studies were performed with partially purified receptors equalized for similar binding capacity , then immunoprecipitated with anti insulin receptor antibody or anti IGF 1 receptor antibody . ^^^ Insulin stimulated tyrosine kinase activity of the receptor preparation for histone H2B phosphorylation was also significantly increased in the LGA group compared to the control . 32P incorporation into beta subunit IGF 1 receptor and IGF 1 stimulated tyrosine kinase activity did not show any significant differences among the three groups . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and IGF 1 receptor signaling in cultured neurons . ^^^ Activated insulin and IGF 1 receptor kinases phosphorylate a 70 kDa protein at early times in culture . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here we describe two additional mAbs , 1H7 and 2C8 , against the IGF 1 receptor that have characteristics different from either alpha IR 3 or our previously reported mAbs . ^^^ Both 1H7 and 2C8 bind to the alpha subunit of the IGF 1 receptor as determined by immunoblotting . ^^^ MAb 1H7 inhibited the binding of IGF 1 and IGF 2 to the IGF 1 receptor while 2C8 had no effect on the binding of either ligand to the receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cross linking studies showed that in cells from diabetic rats , the major band of 140 kd corresponding to the alpha subunit of the IGF 1 receptor increased in density by 50 % compared with those from control rats . ^^^ Since the biological effects of IGF 1 are initiated by its binding to the IGF 1 receptor , which is able to transduce mitogenic and metabolic signals , our results support the hypothesis that the IGF 1 receptor is involved in the development of diabetic vascular complications . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In 3T3 cells constitutively overexpressing the human IGF 1 receptor , called p 6 cells , IGF 1 by itself is fully mitogenic . ^^^ Although bFGF does not bind directly to the IGF 1 receptor , it induces its autophosphorylation . ^^^ Stimulation of p 6 cells by bFGF is not inhibited by an antibody to the IGF 1 receptor that inhibits IGF 1 mediated DNA synthesis , and IGF 1 is not detectable in the medium of bFGF treated p 6 cells . ^^^ Basic FGF also stimulates DNA synthesis in 3T3 cells overexpressing a mutant IGF 1 receptor that does not autophosphorylate in response to IGF 1 and has lost its mitogenic potential . ^^^ Although we were unable to demonstrate directly that bFGF causes transphosphorylation of the IGF 1 receptor , we conclude that in cells overexpressing the IGF 1 receptor , bFGF can stimulate DNA synthesis either by an unknown mechanism or through transphosphorylation of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Fibroblast cell lines were established from mouse embryos homozygous for a targeted disruption of the Igf1r gene , encoding the type 1 receptor for insulin like growth factor 1 ( IGF 1 ) and from their wild type littermates . ^^^ The cells from the wild type embryos ( W cells ) grow in serum free medium supplemented with platelet derived growth factor , epidermal growth factor , and IGF 1 , whereas the cells from Igf1r ( / ) embryos ( R cells ) do not , although they grow at a reduced rate in 10 % fetal calf serum . ^^^ The transformed phenotype is restored if the R cells carrying the SV 40 large tumor antigen are stably transfected with a plasmid expressing the human IGF 1 receptor . ^^^ These results demonstrate that signaling via the IGF 1 receptor is an indispensable component of the SV 40 transformation pathway . ^^^ This conclusion is further supported from the results of antisense RNA experiments with tumor cell lines showing that interference with the function of the IGF 1 receptor has a profound effect on anchorage independent growth , even under conditions that only modestly affect growth in monolayers . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Fetal brown adipocytes bear a high expression of insulin like growth factor receptor ( IGF IR ) , and show a high affinity IGF 1 specific binding to its receptor , and a high number of binding sites per cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Plasma IGF 1 concentrations and IGF 1 receptor binding on mononuclear cells have been studied on bovine leukemia virus ( BLV ) negative ( CO ) , BLV infected aleukemic ( AL ) cows or cows with persistent lymphocytosis ( PL ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Protein microsequencing of human placental IGF 1 receptors purified by immunoaffinity chromatography using IGF 1 receptor specific monoclonal antibody revealed amino acid sequences of both IGF 1 and insulin receptors . ^^^ Thus , the present studies indicate that hybrid receptors purified from human placenta have the functional properties of an IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor is a glycosylated heterodimer which , upon binding with IGF 1 , undergoes tyrosine autophosphorylation . ^^^ EXPERIMENTAL DESIGN : In this study , we have assessed the role of the IGF 1 receptor in the proliferation of ovarian carcinoma cell lines in culture . ^^^ Effects of anti sense and sense oligodeoxynucleotides to IGF 1 receptor RNA were tested . ^^^ Incubation of cells with anti sense oligodeoxynucleotides corresponding to the IGF 1 receptor RNA markedly inhibited cell proliferation both in serum free medium and in the presence of IGF 1 . ^^^ The inhibition of cell growth by the oligodeoxynucleotides corresponded to a reduction in the amount of detectable phosphorylated IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In each case , treatment with anti IGF 1 receptor antibodies blocked cell proliferation . ^^^ Similarly , serum deprivation increased IGF 1 receptor mRNA by 4 fold . ^^^ Collectively , these results support the concept that an IGF / IGF 1 receptor system at least partially mediates SH SY5Y cell proliferation and suggests the importance of IGFs in regulating neuronal growth . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have previously presented evidence for two IGF 1 receptor species in rat skeletal muscle . ^^^ One form of IGF 1 receptor is selectively expressed in fetal and early postnatal life , and the second is present in both fetal and adult animals . ^^^ Anti IGF 1 receptor beta subunit antibodies were generated against synthetic peptides corresponding to residues 1284 1293 and 1308 1318 of the cloned human IGF 1 receptor , and the capacity of these antibodies to interact with the two IGF 1 receptors was investigated . ^^^ The presence of a 95 , 000 M ( r ) IGF 1 receptor beta subunit distinct from the insulin receptor beta subunit in human muscle was confirmed by the demonstration of an IGF 1 sensitive receptor with a beta subunit of this size after insulin receptor immunodepletion . ^^^ The fetal receptor corresponds to the cloned and sequenced IGF 1 receptor , and the primary structure of the adult type receptor has not yet been established . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding of [ 125I ] IGF 1 was inhibited by IGF 1 ( half max . 7 . 5 ng / ml ) , IGF 2 ( half max . 60 ng / ml ) , and insulin and anti IGF 1 receptor antibody ( alpha IR 3 ) . [ 125I ] IGF 2 was inhibited by IGF 2 ( half max . 15 ng / ml ) , IGF 1 ( half max . 500 ng / ml ) , insulin ( half max . 250 ng / ml ) but not by alpha IR 3 . ^^^ Probes were labeled with [ 32P ] dCTP using a random prime labeling procedure : a Pst 1 700 bp fragment of the human IGF 1 cDNA , a 554 bp Pst 1 Sal 1 fragment of the IGF 2 cDNA , a 614 bp Pst 1 fragment of the IGF 1 receptor cDNA and a 663 bp Pst 1 fragment of the IGF II / M6P receptor . ^^^ No signal was detected with the IGF 1 receptor cDNA probe . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity crosslinking studies and immunoprecipitation with antibodies against the Type 1 IGF receptor identified the alpha subunit of the IGF 1 receptor as having a molecular mass of 140 kDa . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 was found to be 3 fold more potent than IGF 2 and 30 fold more potent than insulin , suggesting that the effects of these growth factors are mediated by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The ranking of the affinities of the three isomers for the human IGF 1 receptor was found to be Tyr 24 ( 125I ) > Tyr 31 ( 125I ) > > Tyr 60 ( 125I ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we investigated the status of the ECM proteins and sulfated PGs , and the expression and de novo synthesis of insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) in hypophysectomized ( Hx ) rats . ^^^ The analysis of IGF IR by specific binding studies revealed a decreased concentration of the receptors , but an increased IGF 1 binding affinity , the latter of which probably contributed to the IGF 1 induced accentuated synthesis of renal glomerular PGs in the Hx group . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cellular localisation of IGF 1 receptors was seen in the lamina propria by IGF 1 receptor immunostaining and ligand binding of biotinylated IGF 1 . ^^^ IGF 1 receptor immunostaining in the spleen showed receptor localisation to the splenic pulp thus pointing to macrophages as the possible IGF 1 receptor positive cells in the lamina propria . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The distribution and regulation of mRNA for the IGF 1 receptor ( IGF 1 R ) in the adult rat brain were studied by in situ hybridization with a 35S labelled cRNA probe . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor ( IGF 1 ) receptor contains an NPXY sequence ( residues 947 950 ) in the immediate submembranous domain , and we sought to determine whether these residues play a role in facilitating ligand mediated internalization of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
After short and long term IGF 1 administration the IGF 1 receptor binding capacity as well as the number of IGF receptor sites decreased to levels found in control subjects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ventricular IGF 1 receptor mRNA levels were unchanged over the time course studied . ^^^ CONCLUSIONS : We conclude that ( 1 ) hypertension induces significant increases in cardiac IGF 1 mRNA and protein that occur coordinately with its onset and early in the development of hypertrophy , ( 2 ) IGF 1 mRNA levels normalize as the hypertrophic response is established , ( 3 ) in comparison to IGF 1 , both c myc and IGF 1 receptor genes are differentially controlled in experimental hypertension . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Introduction of the monoclonal antibody alpha IR 3 against human IGF 1 receptor reduced proliferation in the presence of fetal bovine serum ( FBS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To clarify the role of ligand mediated receptor internalization for IGF 1 signaling to GH , human IGF 1 receptor ( IGF IR ) cDNAs mutated in the beta subunit were stably transfected into GC rat pituitary cells . ^^^ Overexpression of wild type IGF IR markedly enhanced IGF 1 suppression of GH 4 fold ( P < 0 . 005 ) compared to that of untransfected cells . ^^^ A mutant IGF IR with a 943Tyr > Ala substitution in the IGF IR submembrane domain only partially suppressed GH ( 73 % of IGF IR wild type ) , while replacement of 957Tyr > Ala or 940Gly > Ala produced IGF IRs that retained enhanced IGF 1 signaling to GH . ^^^ Substitution of 950Tyr > Ala or 1003Lys > Ala in the human IGF IR beta subunit failed to enhance IGF 1 signaling to GH above that of untransfected cells . ^^^ In contrast , substitution of 957Tyr > Ala reduced the internalization of labeled IGF 1 to 35 % that of wild type IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We established HTLV 2 transformed cell lines from 1 Efe Pygmy , 1 African control , and 3 American controls , and quantified in vitro colony formation in response to IGF 1 , GH , and insulin , and assessed IGF 1 receptor binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since GH appears to be able to increase the in vitro effect of both IGF 1 and IGF 2 , we can hypothesize a sensitization of the granulosa cells to the IGF 2 produced by the cells themselves , which acts through the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGFR ) content and its prognostic significance were evaluated in human breast cancer specimens using a sensitive and specific radioimmunoassay ( 5 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of a monoclonal antibody against IGF 1 significantly reduced the effect of DHT , and simultaneous addition of a specific IGF 1 receptor antibody blocked the expected induction of 5 alpha R activity ( control , 4 . 9 + / 0 . 5 ; DHT , 8 . 0 + / 1 . 9 ; DHT plus IGF 1 receptor antibody , 3 . 7 + / 0 . 4 % ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The tryptic phosphopeptide map of the 95 kDa band suggests that it contains both insulin and IGF 1 receptor beta subunits . ^^^ Phosphorylation of the 101 kDa subunit is more responsive to IGF 1 than to IGF 2 or insulin , indicating that it is a second IGF 1 receptor beta subunit . ^^^ Its immunoreactivity and phosphopeptide map are virtually identical to those of the 101 kDa IGF 1 receptor beta subunit from permissive cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , monoclonal antibodies that interfered with the function of either the IGF 1 receptor ( alpha IR 3 ) or E cadherin ( HECD 1 , MB 2 ) blocked the effect of IGF 1 on aggregation . ^^^ The insulin effects were presumably not mediated by the IGF 1 receptor , since they could not be blocked by an antibody against this receptor ( alpha IR 3 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These include the events occurring after the IGF 1 receptor is activated by its ligand , the role of anti oncogenes in preventing the activation of growth factor receptors , the mechanism ( s ) by which some proto oncogenes may short circuit the cell cycle and the use of peptide analogues and the antisense strategy to study and to regulate cellular proliferation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Pituitary and hypothalamic insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor expression in food deprived rats . ^^^ Tissues were processed for measurement of steady state levels of : ( a ) IGF 1 and IGF 1 receptor mRNA ( by solution hybridization / RNase protection assay ) ; ( b ) IGF 1 in serum and tissue extracts ( by RIA ) and ( c ) IGF 1 displaceable [ 125I ] IGF 1 binding to plasma membrane preparations . ^^^ Kidney IGF 1 mRNA levels were reduced 80 % in food deprived rats with a concomitant increase in IGF 1 receptor concentration and mRNA levels . ^^^ A modest increase was seen in pituitary IGF 1 receptor concentration ; however , IGF 1 receptor mRNA levels were not changed . ^^^ Hypothalamic IGF 1 mRNA content was reduced in 72 h food deprived rats while IGF 1 receptor binding capacity and mRNA were unaffected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the cerebellum , for example , [ 125I ] IGF 2 receptor binding sites are concentrated in the granular cell layer , [ 125I ] insulin binding sites are localized primarily in the molecular layer , whereas [ 125I ] IGF 1 receptor binding sites are noted in relatively high amounts in granular as well as molecular cell layers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
High resolution microscopy in conjunction with colloidal gold labeled insulin like growth factor 1 ( IGF 1 ) has been used to provide evidence that the IGF 1 receptor is first detected in 8 cell stage mouse embryos , confirming the results of previous reverse transcriptase polymerase chain reaction ( RT PCR ) studies . ^^^ Specificity for the IGF 1 receptor was demonstrated by displacement with unlabeled IGF 1 and dual labeling experiments with colloidal gold labeled or unlabeled insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The increased up regulation on IGF 1 receptors and the absence of neuroprotection by IGF 1 suggest that the intracellular signal transduction chain activated by the IGF 1 receptor may be interrupted . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The peptide did not affect IGF 1 receptor autophosphorylation or ligand induced phosphorylation of an endogenous substrate , pp 185 , in vivo . ^^^ In conclusion , 1 ) the MHC 1 derived peptide Dk ( 62 85 ) inhibits IGF 1 internalization in a dose responsive fashion ; 2 ) Dk ( 62 85 ) does not affect receptor kinase activity , as IGF 1 receptor autophosphorylation and endogenous substrate phosphorylation are unaltered ; and 3 ) Dk ( 62 85 ) stimulates glucose transport by itself , but inhibits IGF 1 stimulated transport . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and insulin at equimolar concentrations ( 25 micrograms / l and 20 micrograms / l respectively ) were almost equipotent after 0 . 5 h but after 4 h incubation IGF 1 was 17 fold more potent , suggesting that this ' late ' effect was mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The increase in DNA synthesis was significantly inhibited either by antibody to the IGF 1 receptor or by the tyrosine kinase inhibitor , methyl 2 , 5 dihydroxycinnamate ( 2 , 5 MeC ) . ^^^ Whereas the increases in DNA synthesis and p 53 phosphorylation were inhibited by antibody to the IGF 1 receptor and by 2 , 5 Mec , the nuclear exclusion of p 53 was prevented by the antibody and also , although not significantly , by 2 , 5 Mec . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Detailed receptor assays performed on microsomal and plasma membranes gave evidence that 125I IGF 2 binds with high affinity ( 70 80 pM ) to the IGF 1 receptor and with low affinity ( 2 4 nM ) to the IGF 2 receptor , and not conversely . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Modulation of expression of insulin and IGF 1 receptor by Epstein Barr virus and its gene products LMP and EBNA 2 in lymphocyte cell lines . ^^^ In general , there was a correlation between total receptor concentration and the level of insulin or IGF 1 receptor mRNAs , although in one cell line insulin binding increased while receptor mRNA levels decreased slightly , suggesting posttranslational effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of GTP gamma S to the thyroid stimulating hormone primed cell membranes resulted in a decreased affinity of IGF 1 receptor binding , and the dissociation constant ( Kd ) increased from 0 . 46 nM to 3 . 1 nM . ^^^ Lithium lowered the affinity of IGF 1 receptor binding and the Kd ( 3 . 4 nM ) was in the same range as that in the presence of GTP gamma S . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Purified insulin receptor and IGF 1 receptor phosphorylated recombinant baculovirus produced IRS 1 on similar sites in vitro , and phosphorylated baculovirus produced IRS 1 bound PtdIns 3 ' kinase activity from lysates of quiescent cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Whereas only a small amount of PtdIns 3 kinase is found associated with the insulin and IGF 1 receptor , a considerable PtdIns 3 kinase activity is immunoprecipitated by an antibody raised against IRS 1 . ^^^ Since IRS 1 seems to be the connection between PtdIns 3 kinase and insulin or IGF 1 receptor , we used reconstitution experiments to characterize the implication of IRS 1 in the activation of PtdIns 3 kinase . ^^^ The interaction between PtdIns 3 kinase and IRS 1 phosphorylated by the insulin or the IGF 1 receptor results in the activation of PtdIns 3 kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , insulinlike growth factor 1 , ( IGF 1 ) , IGF 1 receptor , and IGF 2 receptor messenger RNAs were expressed in the epithelial cells of both the control , uninjured tissues and in tissue specimens obtained after injury . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since many of the actions of IGF 2 are mediated through activation of the IGF 1 receptor ( IGF IR ) , we have measured the levels of IGF IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization / RNase protection assays . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report here that non SCLC cell lines ( A 549 , A 427 , SK LU 1 ) expressed the IGF 1 receptor protein , and IGF 1 stimulated the proliferation of low density plated ( 2000 cells / cm2 growth area ) carcinoma cells by 1 . 6 to 3 fold above control after a 4 day incubation period under serum free conditions ( A 549 , A 427 ) or in the presence of 0 . 25 % serum ( SK LU 1 ) . ^^^ Both stimulatory effects were neutralized by an anti IGF 1 antibody , suggesting that the fibroblast derived factor mediated its activity via the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The potential role of insulin and IGF 1 receptor tyrosine kinases in the bovine luteal cell was investigated in terms of autophosphorylation of the receptor and phosphorylation of endogenous and exogenous substrates . ^^^ This phosphoprotein was further identified as the autophosphorylated beta subunit of the insulin / IGF 1 receptor by immunoprecipitation with an anti beta subunit receptor antibody . ^^^ These findings demonstrate a cascade of insulin and IGF 1 receptor tyrosine kinase mediated pathways in the bovine luteal cell , manifested as increased activity of signal transduction enzymes and increased DNA synthesis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Their actions are mediated primarily by their interactions with the type 1 IGF receptor ( IGF 1 receptor ) , a transmembrane tyrosine kinase . ^^^ The ligands and the IGF 1 receptor are structurally related to insulin and to the insulin receptor , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Pietrzkowski et al . ( Cell Growth Differ 92 : 199 205 , 1992 ) found that these cells , overexpressing the IGF 1 receptor , can also be induced to grow by the addition of EGF . ^^^ In 3T3 cells overexpressing the EGF receptor , a functional IGF 1 receptor is still required for growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mice carrying null mutations of the genes encoding insulin like growth factor 1 ( Igf 1 ) and type 1 IGF receptor ( Igf1r ) . ^^^ Igf 1 ( / ) / Igf1r ( / ) double mutants did not differ in phenotype from Igf1r ( / ) single mutants , while in Igf 2 ( ) / Igf1r ( / ) and Igf 1 ( / ) / Igf 2 ( ) double mutants , which are phenotypically identical , the dwarfism was further exacerbated ( 30 % normal size ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and the related growth factors , insulin and IGF 2 , inhibited PTH stimulated cAMP production with a rank order of potency of IGF 1 > or = IGF 2 > insulin , indicating that the actions of IGF 1 on SaOS 2 cells were probably mediated by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to determine possible targets for fallopian tube derived IGF 1 we examined the expression of IGF 1 receptor mRNA . ^^^ Northern blot analysis revealed that an 11 kilobase IGF 1 receptor transcript was expressed in the fallopian tube . ^^^ Using a reverse transcriptase polymerase chain reaction , IGF 1 receptor mRNA was also detected in the eight cell but not two cell preimplantation embryo . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Receptors for IGF 1 were visualized on the Schwann cell surface by indirect immunofluorescence staining using anti human IGF 1 receptor antibodies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor tyrosine autophosphorylation was completely prevented by ethanol both in intact cells and in immunopurified IGF 1 receptor preparations . ^^^ Ethanol also inhibited the stimulation of IGF 1 receptor autophosphorylation and the corresponding growth of p 6 cells induced by IGF 2 . ^^^ These findings demonstrate that ethanol at low concentrations markedly inhibits IGF 1 receptor autophosphorylation and IGF 1 mediated cell growth . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 was found to be 3 times more potent than IGF 2 and 30 times more potent than insulin , suggesting that the effects of these growth factors are mediated by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Xenopus oocytes from unprimed frogs possess insulin like growth factor 1 ( IGF 1 ) receptors but lack insulin and IGF 1 receptor substrate 1 ( IRS 1 ) , the endogenous substrate of this kinase , and fail to show downstream responses to hormonal stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In general , the dephosphorylation of IGF 1 receptor follows a pattern similar to that of insulin receptor except in red skeletal muscle in which it is not modified . ^^^ Pregnancy also induces alterations of liver PTP ases similar to those elicited by diabetes with a 50 % reduction of insulin and IGF 1 receptor dephosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our results indicate that the drug does not affect the IGF 1 receptor ( IGF 1 R ) , but binds directly to the IGF 1 peptide . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
At the time point and STZ dosages at which kidney IGF 1 mRNA induction was most dramatic , renal IGF 1 receptor mRNA was only minimally changed , and renal alpha tubulin mRNA was modestly reduced . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MAIN OUTCOME MEASURE : The expression of IGF 1 receptor and insulin receptor transcripts were analyzed by Northern blot . ^^^ RESULTS : In the separated thecal tissue both IGF 1 receptor and insulin receptor transcripts were detected . ^^^ CONCLUSION : The present study demonstrates that both insulin and IGF 1 receptor genes are expressed and that insulin and IGF 1 can stimulate steroid production in human thecal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Competitive binding studies and affinity labelling of brain membranes from Cottus scorpius ( sea scorpion ) , Raja clavata ( ray ) and Myxine glutinosa ( atlantic hagfish ) identified a mammalian type 1 or IGF 1 receptor by its binding specificity and the molecular size of its alpha subunit . ^^^ In all three species the binding of 125I IGF 1 and 125I IGF 2 was significantly higher in brain compared with liver and gastrointestinal tract , and the IGF 1 receptor could only be identified with certainty in Raja liver . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
All three cell lines produce substantial amounts of insulin like growth factor 1 ( IGF 1 ) that is secreted in the medium and they all display constitutively autophosphorylated IGF 1 receptors ; two of the cell lines overexpress IGF 1 receptor RNA . ^^^ The growth of all three cell lines is inhibited by an antisense oligodeoxynucleotide to IGF 1 receptor RNA or by peptide analogues of IGF 1 that compete with IGF 1 binding to its receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and IGF 1 receptor function among type 2 diabetic responders and nonresponders to glyburide . ^^^ Studies of the IGF 1 receptor likewise did not reveal differences between the two diabetic groups . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The extent of hybrid receptor formation was proportional to the molar ratio of the insulin and IGF 1 receptor expression plasmids used for transfection of cultured fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor mRNA ( 11 . 5 , 6 . 5 and 4 . 5 kb ) and affinity labeled receptor ( approximately 125 kDa ) protein levels declined during the neonatal stages of development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Preincubation with an IGF 1 receptor antibody ( alpha IR 3 ) completely prevented the proliferative effect of IGF 1 , IGF 2 , and hGH , indicating that hGH acts via autocrine or paracrine induction of IGF . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A 120 kDa band , the alpha subunit of the IGF 1 receptor , was specifically labeled in Rat 1 plasma membranes by this photoprobe . ^^^ The labeling of this band was reduced by hIGF 1 at 1 nM and completely abolished by hIGF 1 , but not insulin , at 100 nM , indicating the specificity of the photolabeling of the IGF 1 receptor by this fully active IGF 1 photoprobe . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have analysed the expression of the IGF 1 receptor gene in lymphocytes of patients with low levels of circulating IGF 1 ( four patients with isolated GH deficiency ( IGHD ) and one Laron type dwarf ( LTD ) ) in comparison with a control group exhibiting normal serum IGF 1 levels and endocrine profiles . 125I Labelled IGF 1 binding assays were performed on erythrocytes to determine the number of IGF 1 binding sites per cell and their dissociation constants . ^^^ The levels of IGF 1 receptor mRNA in circulating lymphocytes were determined by an RNA template specific reverse transcription / polymerase chain reaction method . ^^^ There was a statistically significant increase in IGF 1 receptor mRNA levels in lymphocytes from patients with LTD or IGHD when compared with controls ( 3108 . 1 + / 775 . 9 vs 576 . 0 + / 465 . 7 arbitrary units , P = 0 . 006 ) . ^^^ The increased level of IGF 1 binding due to increased IGF 1 receptor gene expression may represent a compensatory up regulation process activated in response to the low levels of IGF 1 in the circulation of patients with LTD or IGHD . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : Messenger RNA expression consistent with both known forms of the insulin receptor , the IGF 1 receptor , and the IGF 2 receptor was observed in human fetal ovaries and uteri at 10 , 15 , 19 , and 22 weeks ' gestation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor concentrations of androgen independent cell lines were significantly higher than those of the androgen dependent cell line . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We determined whether components of the ECM influence IGF 1 receptor expression in IEC 18 rat small intestine crypt cells . ^^^ Messenger RNA ( mRNA ) for IGF 1 receptor was quantified by Northern analysis . ^^^ A 130 , 000 molecular weight protein was identified by cross linking , consistent with the alpha subunit of the IGF 1 receptor . ^^^ Northern analysis revealed that IEC 18 cells cultured on Matrigel had less mRNA for IGF 1 receptor than cells cultured on plastic . ^^^ CONCLUSIONS : The rate of cell proliferation and the composition of the ECM influence IGF 1 receptor expression in IEC 18 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RA induced fast aggregation was not sensitive to cycloheximide , tyrosine kinase inhibitors or antibodies against IGF 1 or against the IGF 1 receptor . ^^^ RA did not stimulate IGF 1 receptor phosphorylation or alter the E cadherin / catenin complex , as evidenced by immunoprecipitation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To better understand the mechanisms responsible for the increase in numbers of fibroblasts and increased collagen synthesis in fibrotic intestitial lung diseases , platelet derived growth factor ( PDGF ) A and PDGF B , PDGF receptor alpha and beta , insulin like growth factor 1 ( IGF 1 ) , and IGF 1 receptor were evaluated immunohistochemically . ^^^ Interestingly , the cellular localizations of PDGF receptor alpha and beta , and of IGF 1 receptor were the same as those of the PDGF and IGF 1 proteins in early stage IPF , whereas these cells were not positive for any of these substances in late stage IPF or normal controls . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Despite the presence of phosphoproteins of the correct size , neither the IGF 1 receptor ( IGF 1 R ) nor the phospholipase C gamma isoform could be identified as tyrosine kinase substrates in either treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The purified proteins have kinase activity , demonstrating that the catalytic domain of IGF 1 receptor , like that of insulin receptor , is active independent of its ligand binding and transmembrane domains . ^^^ Insulin and IGF 1 receptors show distinct preferences for these peptides ; whereas insulin receptor prefers peptides based on Tyr 987 or Tyr 727 of insulin receptor substrate 1 , the IGF 1 receptor preferentially recognizes the Tyr 895 site . ^^^ The catalytic activity of IGF 1 receptor is stimulated approximately 3 . 4 fold by treatment with purified 5 Src , while insulin receptor shows very little effect of Src phosphorylation under these conditions . ^^^ This observation is relevant to recent findings of IGF 1 receptor activation in Src transformed cells , and may represent one method by which Src amplifies its mitogenic signal . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the most striking pattern was exhibited by IGF 1 receptor . ^^^ Our results suggest that induction of IGF 1 receptor mRNA by EGF may be an important event in the establishment of competence by EGF in long term density arrested WI 38 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To address this question we examined IGF 1 receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15 ( 15q26 . 1 > qter ) . ^^^ Quantitative Southern blot analysis of the IGF 1 receptor gene was performed on HindIII digests of fibroblast DNA . ^^^ Radioactivity in the 1 . 7 kilobase receptor fragment in the two patients was 55 % and 51 % of the values in controls , consistent with the absence of one copy of the IGF 1 receptor gene . ^^^ IGF 1 receptor messenger ribonucleic acid levels were quantitated by a solution hybridization / nuclease protection assay . ^^^ Northern blotting demonstrated normal size IGF 1 receptor transcripts and affinity crosslinking of [ 125I ] IGF 1 to Triton 10 100 solubilized fibroblasts demonstrated a normal size receptor in the patients . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The Pygmy T cell lines showed reduced clonal proliferation in response to high insulin concentrations known to act through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Primary cultures of cells from the oPT contained a widespread distribution of cells staining positively with a monoclonal antibody to the human IGF 1 receptor , with the strongest staining occurring over the small phase bright cells that predominate in this culture system and are thought to constitute the melatonin responsive cell type . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To achieve this purpose , we measured , in a model of primary culture of porcine Sertoli cells , the effects of TNF alpha on the IGF system that includes IGF 1 and IGF 2 , IGF binding proteins ( IGFBPs ) , and IGF 1 receptor ( IGF 1 R ) . ^^^ We report that while TNF alpha had no consistent effect on the levels of IGF 1 , IGF 2 , or on IGF 1 receptor ( protein and messenger RNA ( mRNA ) ] , it stimulated IGFBP activity and particularly IGFBP 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 significantly increased thymidine incorporation , and its effect was completely inhibited by IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis of the involvement of different growth factors and oncogenes in thyroid carcinogenesis suggests that genes related to the two receptors concerned with normal TSH stimulated growth , TSH receptor and the IGF 1 receptor may be involved in the progression of thyroid tumours of follicular pathology . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor is also capable of binding IGF 2 and insulin , whereas the EGF receptor is also capable of binding TGF alpha . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
No apparent change in tissue GH receptor , IGF 1 , IGF 1 receptor , IGF 2 , or IGF 2 receptor messenger ribonucleic acids occurred as a result of exercise after the 14 week pretreatment period or after treatment with rhGH or PL . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , thrombin doubled IGF 1 receptor density on vascular smooth muscle cells , without altering binding affinity ( Kd ) . ^^^ These data demonstrate that a functional IGF 1 IGF 1 receptor pathway is essential for thrombin induced mitogenic signaling and support the concept of cross talk between G protein coupled and tyrosine kinase receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In IGF 1 receptor competition studies , IGF 1 , but not relaxin , displaced [ 125I ] IGF 1 from the GC IGF 1 receptor . ^^^ They are the first to show 1 ) a stimulatory effect of relaxin on IGF 1 secretion ; 2 ) the necessity of IGF 1 activity for relaxin induced GC DNA synthesis ; and 3 ) the absence of an effect of relaxin on GC IGFBPs or IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MAIN OUTCOME MEASURES : Steroid hormones , IGF 1 , IGF binding protein ( IGFBP ) , and IGF 1 receptor levels , developmental rate , and cell numbers of embryos . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An overexpressed insulin like growth factor 1 receptor ( IGF IR ) allows cells to grow in IGF 1 only and to form colonies in soft agar . ^^^ Our results show that : ( 1 ) an overexpressed Grb 2 can not replace the IGF IR in IGF 1 mediated mitogenesis ; ( 2 ) Grb 2 also fails to transform either W or R cells ; ( 3 ) Grb 2 and SV 40 T antigen , singly transfected , can not transform R cells , but can do so when combined ; and ( 4 ) SH 3 domain mutants of Grb 2 act as dominant negatives , causing reversion of the transformed phenotype . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Resection resulted in increased steady state colonic IGF 1 mRNA ( 182 % of TX / V ; P < 0 . 01 ) without significantly affecting IGF 1 receptor mRNA expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 receptor mRNA was rarely seen in the glomeruli of control rats . ^^^ IGF 1 receptor mRNA was detected after induction of diabetes in glomerular mesangial , visceral epithelial , and parietal epithelial cells . ^^^ The number of IGF 1 receptor mRNA positive cells in a glomerulus increased significantly at 4 weeks as compared with the control rats . ^^^ Overexpression of IGF 1 receptor in glomerular cells may contribute to the glomerular hypertrophy in diabetic nephropathy . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An IGF 1 receptor blocking antibody inhibited IGF 1 stimulated migration in both cell types . ^^^ We conclude that : 1 ) IGF 1 stimulates migration of these two cell types through the IGF 1 receptor ; 2 ) interaction of vitronectin with the alpha 5 beta 5 integrin or collagen with the alpha 2 beta 1 integrin is necessary for the complete IGF 1 response in MCF 7 cells , and 3 ) because migration represents an in vitro model for metastatic spread , integrins , extracellular matrix proteins , and IGF 1 may play coordinated roles in the metastasis of breast cancer in vivo . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover we demonstrate the capacity of ICI 182 , 780 and ICI 164 , 384 to reduce , in a time dependent fashion , oestrogen and / or IGF 1 stimulated growth of ER+cell lines , possibly by negatively interfering with an IGF 1 like material secretion and IGF 1 receptor number . 4 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the presence of the IGF 1 receptor in muscle accounts for IGF physiological effects in vivo on glucose uptake and glycogen synthesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 produced in the kidney is one component of the intrarenal IGF 1 system comprising the IGF 1 receptor ( IGF IR ) and six IGF binding proteins ( IGFBP ) . ^^^ Because of the physiologic importance of IGF 1 and its potential therapeutic properties , the renal sites of mRNA synthesis for IGF 1 , IGF IR , and IGFBP 1 through IGFBP 5 were characterized in rat kidney by in situ hybridization . ^^^ IGF 1 mRNA was present in the thick ascending limb of Henle in the outer medulla , whereas IGF IR mRNA was diffusely present at low levels throughout the kidney . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factors ( IGFs ) are trophic factors whose growth promoting actions are mediated via the IGF 1 receptor and modulated by six IGF binding proteins ( IGFBPs ) . ^^^ In this study , we observed increased transcripts of both IGF 1 and IGF 1 receptor after rat sciatic nerve transection . ^^^ Northern analysis revealed that SCs expressed IGF 1 receptor and IGFBP 5 . ^^^ Collectively , these data support the concept that , in response to nerve injury , invading macrophages produce IGF 1 and SC express the IGF 1 receptor , to facilitate regeneration . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of tyrosine residues 1250 , 1251 , and 1316 in the carboxy terminus of the IGF 1 receptor . ^^^ Mutations in the human IGF 1 receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine ( yyFH ) , respectively , or replacement of the conserved distal tyrosine ( position 1316 ) with phenylalanine ( yCF ) . ^^^ The yyFH mutation results in an IGF 1 receptor with the amino acids found in the homologous position of the human insulin receptor . ^^^ However , one or both of the proximal tyrosine residues ( positions 1250 and 1251 ) in the carboxy terminus of the IGF 1 receptor are essential for IGF 1 stimulation of mitogenic and tumorigenic pathways . ^^^ Fibroblasts expressing this mutant IGF 1 receptor formed fewer tumors than the negative control cells , whereas cells expressing wild type IGF 1 receptors formed large tumors in all recipient mice injected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 , the IGF 1 receptor ( IGF IR ) , and all six IGFBPs was detected using an ribonuclease protection assay . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , two different IGF 1 analogues differing in the amino terminus that bind equally well to the IGF 1 receptor but poorly to IGFBPs are as effective as IGF 1 at 100 fold lower concentrations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Opposite regulation of IGF 1 and IGF 1 receptor mRNA and concomitant changes of GH receptor and IGF II / M6P receptor mRNA in human IM 9 lymphoblasts . ^^^ Antisense riboprobes for human IGF 1 , IGF 1 receptor , IGF II / M6P receptor , GH receptor and for comparison for human beta actin were synthesized and labeled with 32P . ^^^ Protected fragments of 379 bases and of 420 and 350 bases with the IGF 1 receptor and with the IGF 1 probe respectively and protected fragments of 670 bases and of 51 and 121 bases with the GH receptor and with the beta actin probe were detected . ^^^ Conversely , the expression of IGF 1 receptor mRNA and beta actin mRNA increased by more than 250 % after the withdrawal of serum within 2 and 8 h respectively , while GH receptor mRNA fell within 2 4 h . ^^^ We conclude that IGF 1 and IGF 1 receptor mRNAs are regulated in an opposite direction in serum deprived IM 9 lymphoblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These experiments indicate that certain IGF 1 receptor mutants with loss of function can be reactivated intracellularly by an overexpressed EGF receptor and confirm that the C terminus of the IGF IR is required for its transforming activity . . ^^^ However , if a wild type human IGF 1 receptor is stably transfected into R / EGFR cells , growth in EGF and colony formation in soft agar are restored . ^^^ To determine a possible interaction between the two receptors , we transfected into R / EGFR cells a number of IGF 1 receptor mutants with different impaired functions . ^^^ The only IGF 1 receptor that can not reverse the growth phenotype of R / EGFR cells is a receptor with a point mutation at the ATP binding site . ^^^ IGF 1 receptor mutants that are mitogenic but not transforming made R / EGFR cells grow in EGF only , but were incapable of inducing the transformed phenotype . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have previously determined that compensatory renal growth ( CRG ) during the initial 24 48 h after uninephrectomy ( UNX ) is GH independent in weanling animals , but associated with significant increases in insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression . ^^^ Rapid and sustained increases in steady state renal IGF 1 receptor and IGF 1 messenger RNA ( mRNA ) were observed at 1 and 6 h , respectively , and remained elevated in the remnant kidneys until 72 h post UNX . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The phenotype is reminiscent of those seen in syndromes of insulin resistance or IGF 1 and IGF 1 receptor deficiencies in higher organisms , suggesting a conserved function for this growth factor family in the regulation of growth and body size . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Taken together , these data suggest that the vav proto oncogene is a substrate for the IGF 1 receptor tyrosine++ kinase and may be involved in the signal transduction of IGF 1 in cells of hematopoietic origin . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In both cell lines , 25 mM glucose impaired receptor and insulin receptor substrate 1 phosphorylation by 34 % , but IGF 1 receptor phosphorylation was unaffected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Levels of messenger RNA ( mRNA ) encoding insulin like growth factor 1 ( IGF 1 ) , IGF 2 , IGF 1 receptor , and IGF binding proteins ( IGFBP 1 to 6 ) were determined after OP 1 treatment . ^^^ The level of IGF 1 receptor mRNA was not altered by treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin , IGF 1 and IGF 2 caused down regulation of IGF IR ; the effect is concentration and time dependent . ^^^ IGF 1 , IGF 2 and insulin induced tyrosine phosphorylation of IGF IR . ^^^ Our results indicate that IGF 1 and IGF IR mediate an autocrine growth mechanism in Y 79 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The actions of insulin like growth factor 1 ( IGF 1 ) on protein turnover and of the IGF 1 receptor ( IGF 1R ) were examined in skeletal muscle of rats with chronic renal failure ( CRF ) and sham operated ( SO ) , pair fed controls . ^^^ These data indicate that in skeletal muscle of CRF rats there is resistance to the IGF 1 effects on protein synthesis and degradation and decreased IGF 1 and IGF 1 mRNA levels ; IGF 1R mRNA and number are increased ; but activity of IGF 1R tyrosine kinase is impaired . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , prolonged , but not short term , stimulation with EGF resulted in autophosphorylation of the IGF 1 receptor , and coincubations with both EGF and IGFBP 5 attenuated this effect . ^^^ These data demonstrate that autocrine secretion of IGF 2 in HT 3 cervical cancer cells can participate in EGF induced mitogenesis and suggest that autocrine signals involving the IGF 1 receptor occur `` downstream ' ' of competence growth factor receptors such as the EGF receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reverse transcriptase polymerase chain reaction ( RT PCR ) showed that the TRTC G 1 C A 4 cells contained IGF 1 receptor mRNA with a sequence corresponding to that determined from rat uterus . ^^^ These results demonstrate that the IGF 1 receptor can be expressed in a thyroid carcinoma with an important contribution to cell growth . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We characterized mechanisms of growth control involving insulin like growth factor 1 ( IGF 1 ) , IGF 2 , and IGF 1 receptor ( IGF 1R ) by investigating their expression in human cervical cancer cell lines , primary cervical tumor cell cultures , and normal ectocervical epithelial cells maintained in short term culture . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding of 125I IGF 1 at 4 degrees C confirmed similar higher levels of expression of the IGF 1 receptor at the basolateral surface than at the apical surface . ^^^ These results indicate that the MPRs and the IGF 1 receptor are expressed in a polarized fashion in Caco 2 cells and that the IGF II / CI MPR present on apical membranes , unlike the IGF II / CI MPR expressed on the basolateral surface , is not functional in endocytosing lysosomal enzymes . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To characterize the mechanisms involved , we studied transcription of the IGF 1 receptor gene in rat aortic smooth muscle cells . ^^^ Angiotensin 2 ( 100 nM ) and basic fibroblast growth factor ( 5 ng / ml ) caused a marked increase in IGF 1 receptor messenger RNA ( mRNA ) levels , peaking at 3 h ( 215 + / 16 . 8 % and 85 + / 7 . 4 % above control , respectively ) . ^^^ Nuclear run on assays indicated that angiotensin 2 and fibroblast growth factor stimulated IGF 1 receptor gene transcription by 2 . 1 and 2 . 5 fold , respectively . ^^^ Down regulation of protein kinase C , a serine / threonine kinase that is important in growth factor activated signal transduction , completely inhibited fibroblast growth factor but not angiotensin 2 mediated up regulation of IGF 1 receptor mRNA . ^^^ The protein kinase C inhibitors chelerythrine ( 3 microns ) , calphostin C ( 100 nM ) , and staurosporine ( 10 nM ) also blocked fibroblast growth factor but not angiotensin 2 induction of IGF 1 receptor mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that bpV ( pic ) acts upstream of the Xenopus IGF 1 receptor in the induction of meiotic maturation , presumably by neutralizing an inhibitory protein tyrosine phosphatase ( s ) that may regulate the receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To evaluate whether differentiation of CaCo 2 cells depends on an IGF 2 related pathway , we treated cells with a blocking antibody to the IGF 1 receptor that mediates most IGF 2 biological effects . ^^^ Sustained expression of IGF 2 resulted in : ( a ) increased proliferative rate ; ( b ) high IGF 1 receptor number , even after reaching confluence ; ( c ) increased capability of anchorage independent growth ; ( d ) inhibition of the expression of apoA 1 and SI mRNAs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Myoblast death was prevented by IGF 1 , des [ 1 3 ] IGF 1 , IGF 2 , and insulin with a dose potency consistent with activation of the IGF 1 receptor ; death also could be blocked by the protein synthesis inhibitor , cycloheximide . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An IGF 1 analog with normal affinity for the IGF 1 receptor but reduced affinity for IGFBPs evokes a similar increase . ^^^ Another analog that binds to IGFBPs but not to the receptor has no effect , indicating that this effect of IGF 1 is mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 mRNA is barely detected in control myometrium , is significantly increased by E 2 treatment , and is augmented even more by the combination of E 2 and P 4 treatment , whereas little change is noted in myometrial IGF 2 or IGF 1 receptor mRNA levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF 1R ) in the stressed cells , large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 months of age , and the animals were killed 6 hours , 3 days , and 7 days later . ^^^ After the documentation of cardiac failure , the unaffected myocytes were enzymatically dissociated , and the expression of IGF 1 and IGF 1R was measured at these three time points after surgery . ^^^ Thus , aging may affect the hypertrophic response of myocytes after infarction but has no impact on the ability of the cells to enhance the expression of IGF 1 and IGF 1R , which may sustain only in part the growth reserve mechanisms of the pathological heart . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This event , which was dependent on MVA , took place late in the prereplicative period and was corrected to a significant increase in the expression of de novo synthesized IGF 1 receptor ( IGF 1R ) proteins at the cell membrane . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The inhibition of myogenic differentiation by high level expression of IGFBP 5 could be overcome by exogenous IGFs , with des ( 1 3 ) IGF 1 , an analogue with decreased affinity for IGFBP 5 but normal affinity for the IGF 1 receptor , showing the highest potency . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Chloroquine and ammonium chloride had no effect alone and did not inhibit IGF 1 receptor binding or action in the absence of rhIGFBP 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To localize mRNAs for insulin like growth factor ( IGF ) 1 , IGF 1 receptor ( IGF IR ) , and IGF binding protein ( BP ) 1 to IGFBP 6 in the rat eye . ^^^ METHODS . cDNA sequences for IGF 1 , IGF IR , and IGFBP 1 to IGFBP 6 were used to synthesize 35S CTP labeled antisense and sense probes for in situ hybridization on 5 microns sections of the rat eye , including the retina , choroid , sclera , ciliary body , and cornea . ^^^ Using in situ hybridization , we have demonstrated mRNAs for IGF 1 , IGF IR , and IGFBP 2 to IGFBP 6 in specific histologic layers of the retina , choroid , ciliary body , and cornea in the rat . ^^^ Localization of mRNAs for insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor , and IGF binding proteins in rat eye . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mouse preimplantation embryos express at least two functional cell surface growth factor receptors that are radiosensitive in other cell types , the epidermal growth factor receptor ( EGF receptor ) and the insulin like growth factor 1 receptor ( IGF 1 receptor ) . ^^^ These embryos also express ligands that bind to and activate these receptors , including transforming growth factor alpha ( TGF alpha ) and insulin like growth factor 2 ( IGF 2 ) , which bind to the EGF receptor and IGF 1 receptor , respectively . ^^^ In this work , we tested the hypothesis that IGF 1 receptor and / or EGF receptor function may be impaired to produce the radiation induced competitive cell proliferation disadvantage that is expressed by irradiated embryos that are aggregated with nonirradiated embryos in chimeras . ^^^ Collectively , these results support the following conclusions : ( 1 ) Ligands for the IGF 1 receptor can rescue irradiated embryos from competitive cell proliferation disadvantage in chimeras , while ligands for the EGF receptor can not ; ( 2 ) IGF 1 receptor function and EGF receptor function are affected differently by ionizing radiation with respect to competitive cell proliferation and are affected similarly by ionizing radiation with respect to blastocoele formation ; ( 3 ) EGF receptor dependent stimulation of competitive cell proliferation and cell differentiation are affected differently by ionizing radiation in preimplantation embryos . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : Evidence has been accumulating that in many tumors , insulin like growth factors ( IGFs ) promote cancer cell growth in an autocrine / paracrine manner via the IGF 1 receptor . ^^^ DNA synthesis in PC 3 cells but not in LNCaP and DU 145 cells was significantly inhibited by the IGF 1 receptor specific monoclonal antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of growth hormone deficiency ( GHD ) and treatment with recombinant bovine GH ( bGH ) or human IGF 1 ( hIGF 1 ) for 10 days on the expression of GH receptor ( GHR ) , GH binding protein ( GHBP ) and of insulin like growth factor 1 receptor ( IGF IR ) mRNA was examined using dw / dw and normal Lewis rats . ^^^ IGF IR mRNA was not detected in liver and despite reduced plasma IGF 1 levels and IGF 1 mRNA expression IGF IR mRNA abundance was not changed in nonhepatic tissues by GHD . ^^^ Our data suggest that changes in plasma IGF 1 levels and local IGF 1 mRNA do not influence IGF IR mRNA expression , while GHR and GHBP mRNA expression in different rat tissues are regulated independently . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reverse transcription polymerase chain reaction ( RT PCR ) analyses showed that mRNAs encoding insulin , IGF 2 , insulin receptor , and IGF 1 receptor were present in both precardiac mesoderm and endoderm , as well as in the forming heart at stage 8 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Angiotensin 2 has multiple physiological effects and we have shown recently that its growth promoting effects on vascular smooth muscle require autocrine activation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There was minimal IGF 1 receptor expression in differentiating outer root sheath , hair shaft , and sebaceous epithelial cells . ^^^ IGF 1 receptor expression in non growth activated epidermis of long standing seborrheic keratoses was confined to the basal epidermal layer , as in normal epidermis . ^^^ In contrast , hyperplastic epidermis undergoing `` regenerative ' ' differentiation ( keratin 16+ , Ki67+ suprabasal keratinocytes ) from psoriasis , chronic skin wounds , and plaques of mycosis fungoides consistently showed increased expression of IGF 1 receptor . ^^^ In these conditions , the region of expanded IGF 1 receptor expression delimited the epidermal zone of keratinocyte proliferation . ^^^ In cultured keratinocytes , the subcellular localization of the IGF 1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding , suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It has been previously shown that mitogenic signaling and transforming activity of the IGF IR can be dissociated : a receptor truncated at residue 1229 ( C terminus ) is fully mitogenic , in terms of its response to IGF 1 , but can not transform 3T3 like cells that are devoid of endogenous IGF IRs ( R cells ) . ^^^ We have extended our mutational analysis of the C terminus of the human IGF IR , by stably transfecting several mutant receptors into R cells , and testing the resulting cell lines for IGF 1 mediated mitogenic response and formation of colonies in soft agar . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Epithelial matrix interactions : laminin downregulates enterocyte EGF receptor and IGF 1 receptor expression . ^^^ EGF receptor and IGF 1 receptor expression were decreased in cells grown on laminin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Replacement of residues 28 37 by Gly Gly Gly Gly or deletion of residues 29 41 in the C region had little effect on the kinetic parameters , contrasting with the markedly impaired binding of these analogues to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The growth arrest was partially prevented by addition of high concentrations of insulin like growth factor 1 ( IGF 1 ) to the cells , indicating that MVA depletion may inhibit cell growth through decreasing the number of IGF 1 receptors ( IGF 1R ) at the cell surface . ^^^ Analysis of receptor proteins cross linked with IGF 1 , as well as binding assays and immunocytostaining confirmed that the number of functional membrane bound IGF 1R was substantially reduced . ^^^ The N linked glycosylation and the expression of de novo synthesized IGF 1R proteins at the cell surface as well as the number of IGF 1 binding sites were completely restored upon replenishment of MVA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both the insulin and IGF 1 receptors ( IGF IR ) are overexpressed in breast cancer , and antibody blockade of the IGF IR inhibits the growth of some breast cancer cell lines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factors ( IGFs ) are often essential for the maintenance of the malignant phenotype , and in lung cancer the IGF 1 receptor ( IGF Ir ) is often expressed at high levels . ^^^ A single transduction by Ad IGF Ir / as ( at a multiplicity of infection of 10 : 1 ) decreased the IGF Ir number by about 50 % in human lung cancer cell lines NCI H 460 and SCC 5 , as measured by an 125I labeled IGF 1 competitive binding assay . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Conversely IGF 1 receptor ( IGF 1 R ) , transforming growth factor beta 2 ( TGFB 2 ) , TGFB 2 receptor ( TGFB 2 R ) , 17 beta hydroxysteroid dehydrogenase ( 17 B HSD ) and leukemia inhibitory factor ( LIF ) levels were up regulated in PcDNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVES : We examined the effect of 7 days of hypoxia in the newborn rat on : a ) body , heart , and lung growth ; b ) circulating insulin like growth factor 1 ( IGF 1 ) ; c ) lung , heart , and liver IGF 1 gene expression ; and d ) lung IGF 1 type 1 receptor gene expression and IGF 1 receptor binding . ^^^ The IGF 1 receptor mRNA in the lung was increased by 200 % ( p < . 02 ) in hypoxia compared with controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF1R ) are required for cell growth in vitro , the possibility was raised that an autocrine IGF 1 IGF1R system may be present in vivo and may become activated in viable ventricular myocytes shortly after infarction . ^^^ Therefore , the unaffected myocytes of the left ventricle were enzymatically dissociated and the expression of IGF1R and IGF 1 mRNAs were measured at 12 h and at 1 , 2 3 , and 7 days after surgery . ^^^ Thus , the marked elevation in ventricular loading after coronary occlusion may activate the IGF 1 IGF1R autocrine system of the unaffected cells , modulating the cellular growth processes implicated in short term ventricular remodelling of the infarcted heart . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor gene expression analyzed by Northern blotting revealed that DES treatment increased the level of IGF IR mRNA by 2 fold compared to controls . ^^^ We also tested the effect of ICI compound on the induction of IGF 1 receptor gene . ^^^ The cotreatment of ICI 182780 strongly inhibited DES induced IGF 1 receptor gene expression ( 50 60 % inhibition ) . ^^^ Stimulation of the proliferative activity of renal epithelial cells by stilbene estrogen , its prevention by IGF 1 receptor antibody , and inhibition of DES induced proliferative activity and the expression of IGF 1 receptors by ICI 182780 suggest the possibility that the stimulatory effect of DES on the proliferative activity of renal epithelial cells may be mediated through the up regulation of IGF 1 receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Nephrotic , but not control , rat proximal tubular fluid increases the [ 3H ] thymidine incorporation in cultured tubular cells , and neutralizing IGF 1 receptor antibodies partially inhibit this activity . ^^^ Secretion of the two collagens is in part ameliorated by neutralizing IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) exerts its effect through the IGF 1 receptor . ^^^ To investigate the effects of nutritional status on chicken IGF 1 receptor gene expression , a solution hybridization / RNase protection assay for IGF 1 receptor mRNA was developed . ^^^ A cDNA clone corresponding to the carboxyl terminal region of the IGF 1 receptor was obtained by reverse transcription PCR ( RT PCR ) . ^^^ Sequence analysis of the clone showed that this region of the chicken IGF 1 receptor is highly divergent from the human IGF 1 receptor . ^^^ IGF 1 receptor mRNA was detected in all tissues examined from newly hatched chickens . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The extracellular alpha subunit of the IGF 1 receptor ( IGF IR ) contains an IGF 1 binding domain , and the beta subunit possesses tyrosine kinase activity , which is greatly enhanced when IGF 1 binds to the alpha subunit and leads to its autophosphorylation . ^^^ The importance of IGF 1 as a mitogen throughout development has been clearly demonstrated in IGF 1 and IGF IR knockout mouse studies and also in transgenic mice over expressing IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor signalling : lessons from the somatotroph . ^^^ Structure function studies of the human IGF 1 receptor were performed in stable , GH secreting transfectants expressing either the cDNA encoding the wild type ( WT ) human IGF receptor and exhibiting enhanced IGF 1 responsiveness , or cDNAs encoding IGF 1 receptor mutants and a truncated , kinase deficient receptor ( 952STOP ) . 950Tyr situated on the submembrane receptor domain was found to be critical for transducing the IGF 1 signal to the GH gene . ^^^ Using similar doses of IGF 1 , the IGF 1 receptor cell transfectants also demonstrated ligand dependent activation of ERKs in pituitary cells . ^^^ In conclusion , the pituitary IGF 1 receptor mediates the negative feedback regulation of GH . ^^^ Thus , IGF 1 receptor mass may determine GH responses to malnutrition , pregnancy , and refeeding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Northern analysis demonstrated that mRNA for IGF 1 receptor was expressed by both untreated and TPA treated FLG 29 . 1 cells . ^^^ In addition , the IGF 1 receptor alpha IR 3 antiserum inhibited the IGF 1 induced FLG 29 . 1 cell ' s migratory activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Increased expression of the insulin like growth factor 1 ( IGF 1 ) receptor gene in hepatocellular carcinoma cell lines : implications of IGF 1 receptor gene activation by hepatitis B virus 10 gene product . ^^^ Therefore , the difference observed in 125I labeled IGF 1 binding between SNU 368 and SNU 387 cells was due to an increase in the number of IGF 1 binding sites with no change in affinity for the IGF 1 receptor . ^^^ An enhanced level of IGF 1 receptors in SNU 368 cells was also observed by fluorescence activated cell sorting analysis using a monoclonal antibody against human IGF 1 receptor , alpha IR 3 . ^^^ The level of IGF 1 receptor RNA and the basal IGF 1 receptor gene promoter activity in SNU 368 cells were 5 and 10 times higher than those observed in SNU 387 cells , respectively . ^^^ To substantiate further that HBx could transactivate the expression of the endogenous IGF 1 receptor gene , Hep G 2 cells were transiently transfected with a HBx expression vector . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It has been shown that a melanoma cell line possesses the IGF 1 receptor which plays a role in activation of the chemotactic response . ^^^ Little is known about the in vivo expression of the IGF 1 receptor and its role in melanocytic lesions . ^^^ In an immunohistochemical study , we investigated the expression of IGF 1 receptor in frozen sections of congenital pigmented nevi from 10 patients ( ages 8 months to 4 yrs ) using the monoclonal antibody alpha IR 3 , which specifically recognizes the extracellular alpha subunit of the IGF 1 receptor . ^^^ IGF 1 receptor was found to be widely expressed by the cell surface of the nevus cells . ^^^ This study indicates that in vivo the IGF 1 receptor is widely expressed by congenital pigmented nevus cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF 1 ) mRNA and IGF 1 receptor in trout testis and in isolated spermatogenic and Sertoli cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and insulin regulate glucose transport in mouse blastocysts via IGF 1 receptor . ^^^ The relative potencies of insulin and IGF 1 suggest that the actions of IGF 1 and insulin were both mediated via the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined the precise distribution of insulin like growth factor 1 ( IGF 1 ) mRNA and IGF 1 receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique . ^^^ Expression of IGF 1 receptor mRNA was rarely seen in the glomeruli of control rats . ^^^ IGF 1 receptor mRNA was detected after induction of diabetes in glomerular mesangial , visceral epithelial , and parietal epithelial cells . ^^^ The number of IGF 1 receptor mRNA positive cells in a glomerulus increased significantly , peaking at 4 weeks as compared with the control rats . ^^^ Overexpression of IGF 1 receptor in glomerular cells , especially mesangial and visceral epithelial cells , may contribute to glomerular hypertrophy in diabetic nephropathy . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor signals multiple cascades via its inherent tyrosine kinase activity . ^^^ More studies are required to fully understand the post receptor mechanism involved in IGF 1 receptor signal transduction and the mechanisms whereby the IGFBPs exert their interesting effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Up regulation of nuclear IGF 1 receptor by short term exposure of stilbene estrogen , diethylstilbestrol . ^^^ These data suggest that IGFs may exert their biological effect through the IGF 1 receptor present in the nucleus . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
T 61 tumor growth is also inhibited in animals treated with a monoclonal antibody which blocks binding of ligand to the IGF 1 receptor , which mediates the mitogenic signal of bound IGF 2 through autophosphorylation of its intracellular tyrosine kinase domain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the rat mRNA for the IGF 1 receptor has been identified in the pars tuberalis using in situ hybridization . ^^^ Autophosphorylation of a 97 kDa substrate , compatible with the beta sub unit of the IGF 1 receptor , was increased in the presence of IGF 1 , indicating the existence of functional IGF 1 receptors on the ovine pars tuberalis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus mice bearing a null mutation for the IGF IR gene invariably die shortly after birth , and mice bearing a null mutation for the IGF 1 gene have a high neonatal mortality rate and marked growth retardation [ 158 , 159 ] . ^^^ The development of a specific pharmacologic inhibitor of the IGF IR should allow rational clinical trials to address the function of IGF 1 as a mediator of cardiovascular growth responses . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because ethanol ( ETOH ) delays puberty , an event that is associated with depressed growth rates and decreased growth hormone and luteinizing hormone ( LH ) secretion via actions at the hypothalamic level , we investigated whether this drug is capable of altering the expression of genes encoding IGF 1 in liver and brain , as well as the expression of the type 1 IGF receptor ( IGF 1R ) within the median eminence ( ME ) . ^^^ In contrast , no changes were detected in IGF 1 mRNA expression in the preoptic area and hypothalamus , as well as in IGF 1R mRNA expression within the ME . ^^^ Effect of ethanol on the synthesis of insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor in late prepubertal female rats : a correlation with serum IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By a frame shift mutation , we have engineered a human IGF 1 receptor ( IGF IR ) cDNA that produces a receptor 486 amino acids long ( plus the 30 amino acids of the signal peptide ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 and IGF 1 receptor ( IGF 1R ) genes was identified from H9A RNA using reverse transcription PCR and Northern analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The proestrous change in serum IGF 1 levels was accompanied by a selective increase in IGF 1 receptor ( IGF IR ) mRNA in the ME . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 rapidly stimulated beta chain IGF 1 receptor autophosphorylation , which peaked at a physiological / mitogenic concentration ( 1 . 4 nM ) and also stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^ Tyrosine phosphorylated IRS 1 bound and subsequently activated phosphatidylinositol 3 kinase by 3 . 5 fold , whereas the tyrosine phosphorylated IGF 1 receptor was not directly associated with the p 85 subunit of the phosphatidylinositol 3 kinase . ^^^ Downstream from Ras , IGF 1 increased both Raf kinase and protein kinase C ( PKC ) zeta activities by 3 . 5 fold . ( Bu ) 2cAMP , an inhibitor of IGF 1 induced mitogenesis in fetal brown adipocyte primary cultures , did not block the very early steps of the IGF 1 induced mitogenic cascade , such as IGF 1 receptor autophosphorylation , IRS 1 or SHC tyrosine phosphorylation , and Ras activation to its GTP active form . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There is a high degree of conservation between the deduced polypeptide and the three mammalian sequences previously described for the IGF 1 receptor ( 75 % homology ) even though it is lower than the homology among mammals themselves ( 95 % homology ) . ^^^ IGF 1 receptor messenger RNAs were specifically detected by reverse transcription PCR in oocytes , embryos , and adult liver and muscle . ^^^ Thus , the IGF 1 receptor messenger stock does not seem to increase further beyond this point or may even decrease . ^^^ Therefore , IGF 1 receptor could play a role early on , during oocyte growth , in addition to its involvement in the maturation process . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , but not IGF 2 , was localized to airway epithelium , while IGF IR was localized to perivascular and peribronchial cells , in the lungs of animals breathing air . ^^^ The distribution of IGF IR immunoreactivity was consistent with a paracrine role for IGF 1 in O 2 mediated pulmonary hypertension and airway hyperreactivity , by mediating smooth muscle cell hyperplasia , as well as a role in endothelial cell repair and late pneumocyte hyperplasia . ^^^ The relative insensitivity of IGF IR immunohistochemistry did not allow us to identify cells with low abundance IGF IR , and potential cellular targets for IGF 1 actions after O 2 exposure may be even more extensive than those recognized here . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Coordinate expression of insulin like growth factor 2 ( IGF 2 ) and IGF II / mannose 6 phosphate receptor mRNA and stable expression of IGF 1 receptor mRNA during differentiation of human colon carcinoma cells ( Caco 2 ) . ^^^ The expression of IGF 2 , IGF 1 receptor and IGF II / mannose 6 phosphate receptor ( IGF II / M6P receptor ) mRNA during spontaneous differentiation of the colon carcinoma cell line Caco 2 was measured . ^^^ Expression of IGF 2 mRNA and IGF II / M6P receptor mRNA correlated significantly with the progress of differentiation , while the IGF 1 receptor was stably expressed throughout the culture period and exhibited a crucial role for the survival of Caco 2 cells , as shown by blocking experiments employing the monoclonal anti IGF 1 receptor antibody alpha IR 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of blockade of IGF 1 receptors ( IGF 1R ) on the intimal response was also investigated . ^^^ Anti IGF 1 and anti IGF 1R antibodies reduced SMC replication by 50 % and 90 % , respectively . ^^^ A D amino acid analog of IGF 1 , JB 3 , inhibited SMC replication and dose dependently inhibited insulin receptor substrate 1 ( IRS 1 ) and IGF 1R phosphorylation in vitro . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , an IGF 1 analogue that inhibits the autophosphorylation of the IGF 1 receptor blunts the insulin mediated increase in CPT 1 and 2 activities by > 70 % . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Primary cultures of stromal vascular ( S 5 ) cells derived from fetal and postnatal adipose tissue were established and exposed to test media ( different concentrations of pig serum with or without IGF 1 ) for morphological study or to serum free media for measuring IGF 1 receptor binding and IGF 1 & IGFBPs secretion . ^^^ The changes in IGF 1 receptor binding and IGF 1 and IGFBP secretion by preadipocytes may account for altered response of preadipocytes to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Localization of insulin like growth factor ( IGF 1 ) and IGF 1 receptor expression in human corpora lutea : role on estradiol secretion . ^^^ MAIN OUTCOME MEASURES : Expression of IGF 1 and IGF 1 receptor messenger RNAs ( mRNAs ) by in situ hybridization . ^^^ Concentration of IGF 1 receptor and binding characteristics . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that the expression of AT 2 is regulated by at least two mechanisms , that is , IGF 1 receptor dependent and IGF 1 receptor independent , and that the former may play an important role in the expression of AT 2 in VSMC . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This two hybrid system ( the interaction trap ) utilizes a hybrid protein containing the LexA DNA binding domain fused to the intracellular portion of the IGF 1 receptor ( LexA IGFIR beta ) and hybrids containing an activation domain fused to either IRS 1 ( Ad IRS 1 ) , Shc ( Ad Shc ) , or a cDNA library . ^^^ We have used the yeast two hybrid system to study the interaction between the IGF 1 receptor and two putative substrates , IRS 1 and Shc . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both undamaged and damaged utricles showed mRNA for Insulin receptor , IGF 1 receptor , FGF receptor 1 , EGF receptor , and PDGF alpha receptor . ^^^ Preliminary evidence suggests that IGF 1 receptor message also may be lowered in neomycin damaged epithelia . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study we investigated the expression and function of the IGF 1 receptor during transformation of isolated and cultured hepatic stellate cells . ^^^ IGF 1 receptor protein decreased stage dependently down to 0 . 5 at the 4th day and about 0 . 17 at the 8th day . ^^^ Northern blot analyses revealed distinct upregulation of IGF 1 receptor mRNA level during culture . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The relative affinity of the IGF 1 receptor for IGF 1 , IGF 2 , and insulin was typical of type 1 binding ( IGF 1 > IGF 2 > insulin ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor beta subunit , insulin receptor substrate 1 ( IRS 1 ) , and mitogen activated protein ( MAP ) kinase were all phosphorylated in response to 6 . 5 nM IGF 1 after 10 min incubation . ^^^ In contrast , the treatment with 23 nM TNF alpha failed to phosphorylate either IGF 1 receptor beta subunit or IRS 1 but did phosphorylate MAP kinase as much as IGF 1 did . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Data from study of type 1 IGF receptor ( IGF 1R ) knockout mice indicate that this receptor mediates most IGF 1 and IGF 2 growth promoting actions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The proliferative response of Efe B lymphoblasts was similar to that of control B lymphoblasts when incubated with another growth factor , phorbol 12 myristate 13 acetate , which does not activate the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and IGF 1 receptor binding were characterized in cardiac muscle cells isolated from the brown trout , Salmo trutta fario . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
TNF induced cytotoxicity of 3T3 cells that overexpress the human IGF 1 receptor ( p 6 cells ) was prevented by IGF 1 alone in the absence of serum . ^^^ The specific protective action of the IGF 1 receptor was demonstrated further by the marked sensitivity to TNF of embryo fibroblasts derived from mice with targeted disruption of the IGF 1 receptor ( R cells ) but not of fibroblasts derived from wild type littermates or R cells transfected with the cDNA for the human IGF 1 receptor . ^^^ The results demonstrate a specific role for the IGF 1 receptor in the protection against TNF cytotoxicity . ^^^ This action of the IGF 1 receptor is mediated by protective cytosolic proteins that exhibit a high rate of turnover and whose levels are regulated principally by factors within serum other than IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
High glucose levels progressively increased the medium content of IGF 1 and the mRNA levels for IGF 1 and IGF 2 , increased IGF 1 and IGF 2 binding and IGF 1 receptor gene expression , and reduced IGF binding protein production . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGFBP 2 and IGFBP 1 both inhibit this IGF 1 receptor mediated stimulation . ^^^ The mechanisms by which the IGF 1 receptor and integrin receptors interact are not yet known . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Compared to the contralateral kidney , the injured kidney showed an increase in IGF 1 receptor number without a change in IGF 1 receptor mRNA levels , a decrease in IGF 1 mRNA and IGF 1 protein levels , a decrease in growth hormone ( GH ) receptor mRNA abundance and receptor binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have previously reported the expression of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) mRNA in some MM cell lines . ^^^ We report that all cell lines expressed IGF 1 and IGF IR mRNA and protein . ^^^ An IGF IR blocking antibody inhibited both the IGF 1 induced and spontaneous growth of LP 1 , and Karpas 707 , while the EJM cell line was unaffected by the addition of the antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In rats with PAN nephropathy , administration of rhIGF 1 increased IGF 1 and GH receptor gene expression , without altering the steady state level of IGF 1 receptor mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In cells incubated with IL 1 beta ( 100 U / ml ) , insulin receptor ( IR ) protein and messenger RNA were increased by 100 % , while IGF 1 receptor protein and transcript were not significantly changed . ^^^ Incubation of MCF 7 cells with IL 1s led , however , to a significant inhibition of IR and IGF 1 receptor autophosphorylation ( 55 % ) and phosphotransferase activity ( 65 % ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To characterize further the role of IGF 2 in the regulation of fetal adrenal growth , we investigated the expression of the messenger RNAs ( mRNAs ) encoding IGF 1 , IGF 2 , IGF 1 receptor ( IGF IR ) and IGF binding protein ( IGFBP ) 1 6 in the fetal rhesus monkey adrenal in vivo from 109 days of gestation until term ( 165 + / 5 days ) using in situ hybridization . ^^^ Role of insulin like growth factors ( IGFs ) , IGF 1 receptor , and IGF binding proteins in growth regulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similar expression patterns of the mRNA encoding IGF 1 receptor and IGF 2 receptor were observed . ^^^ Reversion by exogenous IGF 2 was abolished by a monoclonal antibody against IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have investigated the autocrine regulation of insulin like growth factor 2 ( IGF 2 ) signaling by the insulin like growth factor 1 receptor ( IGF IR ) and the insulin like growth factor II / mannose 6 phosphate receptor ( IGF IIR ) in MCF 7 breast cancer cells , employing retroviruses encoding both IGF 1 , IGF 2 , and IGF 1 and 2 mutants with reductions in affinity for either the IGF IR or the IGF IIR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Enhancement of thymulin secretion induced by GH , as well as the stimulation of thymocyte adhesion to thymic epithelial cells can be prevented in vitro by treatment with antibodies for IGF 1 or IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since both receptors are exposed to the maternal circulation , it has been suggested that maternal metabolic abnormalities might affect placental insulin ( HIR ) and IGF 1 ( IGF 1R ) receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The concentration of insulin required to produce this effect suggests that it is acting via its ability to bind to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the current study , the IGF 1 dependent proliferation of mouse BALB / c3T3 cells was completely inhibited by ethanol , but the growth of BALB / c3T3 cells that overexpress the IGF 1 receptor ( p 6 cells ) was only partially inhibited by ethanol BALB / c3T3 cells that simultaneously overexpress both the IGF 1 receptor and IGF 1 were insensitive to growth inhibition by ethanol . ^^^ In p 6 cells , increasing concentrations of IGF 1 overcame the inhibition of IGF 1 receptor tyrosine autophosphorylation in the presence of ethanol . ^^^ The importance of the IGF 1 receptor as a specific target for ethanol was further investigated in C 6 rat giloblastoma cells that respond mitogenically to both epidermal growth factor ( EGF ) and IGF 1 . ^^^ The mitogenic response of C 6 cells to EGF was abrogated in cells expressing antisense mRNA to the IGF 1 receptor . ^^^ Thus , EGF action in these cells is dependent on activation of an IGF I / IGF 1 receptor autocrine pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cryostat sections from patellar cartilage were incubated either with IGF 1 receptor antibody or biotinylated IGF 1 . ^^^ Using IGF 1 receptor antibody , IGF 1 receptors were found on the cell membrane of chondrocytes in the middle and deeper cartilage zones , whereas intracellular staining was highest in chondrocytes of superficial zones . ^^^ In cartilage from inflamed knee joints staining with the use of IGF 1 receptor antibody did not change significantly , whereas a pronounced increase in staining was noted with biotinylated IGF 1 in chondrocytes of the middle and deeper zones of cartilage . ^^^ It is concluded that the staining patterns obtained with the use of IGF 1 receptor antibody and biotinylated IGF 1 are remarkably different , suggesting that the latter also detects IGF binding proteins . ^^^ The results suggest that joint inflammation has no consistent effect on IGF 1 receptor expression but may induce a significant upregulation of IGF binding proteins in chondrocytes of the middle and deeper zones of cartilage . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The phosphorylation of insulin like growth factor binding protein 1 ( IGFBP 1 ) alters its binding affinity for insulin like growth factor 1 ( IGF 1 ) and thus regulates the bioavailability of IGF 1 for binding to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this patient ' s cells , both of these hormones increased 3H thymidine incorporation , and the effect was blocked by alpha IR 3 , a monoclonal antibody that blocks activation of the IGF 1 receptor . ^^^ These findings confirmed the absence of the insulin receptor and indicated that insulin acts here through activation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined the possible role of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF Ir ) during multistage carcinogenesis in mouse skin . ^^^ For this purpose , the expression of both IGF 1 and IGF Ir was investigated in mouse skin during tumor promoter treatment and in primary papillomas and squamous cell carcinomas ( SCCs ) obtained from SENCAR mice treated with standard initiation promotion regimens . ^^^ Single and multiple topical treatments with 3 . 4 nmol of 12 O tetradecanoylphorbol 13 acetate ( TPA ) had no effect on dermal or epidermal IGF 1 and IGF Ir mRNA levels . ^^^ The levels of an 11 . 0 kb IGF Ir transcript were also elevated ( 2 . 5 to 8 fold ) in some papillomas ( 20 % ) and SCCs ( 55 % ) , but the percentage of tumors exhibiting this property ( 32 % of all tumors examined ) was lower than the percentage overexpressing IGF 1 . ^^^ These data suggest that altered expression of IGF 1 and IGF Ir may play a role in multistage carcinogenesis in the mouse skin model . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Preexposure of macrophages with specific antibodies against IGF 1 and IGF 1 receptor before IGF 1 addition resulted in a complete abrogation of the stimulatory effect of IGF 1 on TNF alpha production , indicating that specific binding of IGF 1 to its receptor is required for macrophage TNF alpha induction by IGF 1 . ^^^ Taken together , these results demonstrate that IGF 1 is a monocyte / macrophage activating factor that enhances TNF alpha production , and that such effect is mediated via the IGF 1 receptor and involves tyrosine kinase activation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tyrosine phosphorylation of p 95 ( IGF 1 receptor beta subunit ) was rapidly and dose dependently increased in response to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , IGF 2 < and IGF 1 receptor messenger RNAs ( mRNAs ) were coexpressed in granulosa cells of developing and dominant follicles through the follicular phase . ^^^ IGF 1 and IGF 1 receptor mRNAs were selectively concentrated in healthy follicles , whereas IGF 2 mRNA was found in all follicles regardless of incipient or overt atresia . ^^^ In summary , there is selective expression of IGF 1 , IGF 1 receptor , and IGFBP 2 and 4 mRNAs during the process of follicular selection in the gilt ovary , with IGFBP 4 expression being closely associated with follicular selection and luteinization . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Finally , using several insulin and IGF 1 receptor mutants , we found that the kinase regulatory autophosphorylation sites play an important role in the interaction of these receptors with the SHP 2 SH 2 domain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because IGF 1R activated by its ligands ( IGF 1 and IGF 2 ) protects cells from apoptosis , the role of the IGF 1R and E 6 in transformation by E 7 is probably related to the recruitment of survival pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In non disease states the insulin receptor is primarily involved in metabolic functions whereas the IGF 1 receptor mediates growth and differentiation . ^^^ Furthermore IGF binding proteins are specific for IGF 1 and IGF 2 thereby modulating the binding of the IGFs to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and IGF binding protein ( IGFBP ) mRNAs in the rhesus monkey placenta suggests a paracrine mode of IGF IGFBP interaction in placental development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Many reports suggest that IGF 2 transduces its effects through the IGF 1 receptor , while others show that IGF 2 utilizes the type 2 receptor to affect cellular activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study examined the regulation of expression of IGF 1 receptor on bronchial epithelial cells by eosinophil granule proteins was examined . ^^^ ECP significantly induced IGF 1 receptor expression on bronchial epithelial cells compared with unstimulated cells . ^^^ These findings suggest that eosinophils participate in the repair process of injured bronchial epithelial cells in the inflamed focus through augmentation of IGF 1 receptor expression by suboptimal degranulation of eosinophil granule proteins , e . g . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNA content of IGF 1 receptor in the testis and heart of the rats fed on the 12 % gluten and protein free diets was significantly larger than those of the rats fed on the 12 % casein diet . ^^^ Whereas in other tissues examined , IGF 1 receptor mRNA content did not change significantly under the different nutritional conditions . ^^^ The amount of IGF 1 receptor in these tissues and the affinity to IGF 1 were determined by measuring the amount of 125I labelled IGF 1 bound to solubilized IGF 1 receptor . ^^^ The affinity of IGF 1 receptor to IGF 1 in each tissue under the various nutritional conditions did not show any marked differences . ^^^ These results indicate that the synthesis of IGF 1 receptor is regulated in a distinctive way in each tissue in response to protein nutrition , and suggest that the regulation may have some physiological meaning in signal transmission of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We also observed an IGF 1 receptor form bearing unusual high affinity for IGF 2 : the binding of [ 125I ] IGF 1 on this receptor was preferentially displaced by IGF 1 but that of [ 125I ] IGF 2 was mostly inhibited by IGF 2 , suggesting that the two tracers did not bind on the same epitopes . [ 125I ] IGF 2 binding to this receptor was greater on SSM than on FSM membranes . ^^^ Autophosphorylation of WGA purified receptors revealed an approximately 400 kDa band after SDS PAGE under nonreducing conditions , which corresponded to the alpha 2 beta 2 form of the IGF 1 receptor , and two beta subunit moieties of Mr 101 and 105 kDa under reducing conditions in both SSM and FSM extracts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity cross linking studies revealed a labelled band of approximate relative molecular mass 135000 , corresponding to the known alpha subunit of IGF 1 receptor . ^^^ This band was significantly inhibited dose dependently by the IGF 1 receptor monoclonal antibody alpha IR 3 or native IGF 1 , suggesting that the IGF 1 binding component in the membrane of stromal cells has the identity of the alpha subunit of IGF 1 receptor . ^^^ These data show that the IGF 1 receptor is a functionally integral component of the stromal cell membrane structure , and its expression might be directly modulated by progesterone and , therefore , might play an important role in the preparation of the stroma for successful embryo implantation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To analyze IGF 1 receptor characteristics , the unexpected interference of a huge presence of IGF binding proteins at the cell membrane was avoided using labeled Long R 3 IGF 1 instead of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Interestingly , by itself alphaIR 3 acted as a weak agonist and induced a modest increase in the cellular content of VEGF mRNA . alphaIR 3 also promoted tyrosine phosphorylation of the beta subunit of the IGF 1 receptor , and the magnitude of this response was comparable with that induced by IGF 1 . ^^^ These observations point to a nonlinear relationship between activation of the IGF 1 receptor and induction of VEGF mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An IGF 1 receptor blocking antibody completely abrogated the IGF 1 induced response suggesting that the effect was specifically IGF 1 receptor mediated . ^^^ We conclude that PGE 2 may act as a secretagogue of IGF 1 and that the latter growth factor may mediate , via an autocrine loop and the IGF 1 receptor , at least some of the anabolic effects of the eicosanoid on cartilage metabolism . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
GH stimulates the healing of colonic anastomoses either directly or through insulin like growth factor 1 ( IGF 1 ) since specific GH receptor as well as IGF 1 receptor have been demonstrated in colon . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The developmental pattern of insulin like growth factor 1 receptor ( IGF IR ) and plasma IGF 1 concentrations were examined in longissimus dorsi ( LD ) , trapezius ( TR ) , and liver from the last third of gestation up to 1 year of age in male Large White ( LW ) and Meishan ( MS ) pigs . ^^^ In displacement experiments , data indicated that IGF 1 bound specifically to IGF IR in both prenatal and postnatal tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : To determine the expression of the insulin like growth factors ( IGFs ) and the IGF 1 receptor in primitive neuroectodermal tumor cell lines and to assess the importance of these proteins in the growth of cell lines in vitro . ^^^ Expression of IGF 1 receptor was detected in all three cell lines . ^^^ CONCLUSION : The IGF 1 receptor is expressed by primitive neuroectodermal tumor cell lines in vitro . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The goal of the present study was to analyze the mechanistic basis and functional significance of the Src induced phosphorylation and activation of the IGF 1 receptor . 1 ) We mapped the sites of IGF 1 receptor autophosphorylation to peptides representing three different receptor domains : tyrosines 943 and 950 in the juxtamembrane region ; tyrosines 1131 , 1135 , and 1136 within the kinase domain ; and tyrosine 1316 in the carboxyl terminal domain . ^^^ The carboxyl terminal site , although phosphorylated in vitro and in src transformed cells , was not a major site of ligand induced phosphorylation in vivo . 2 ) We determined that the sites of Src induced phosphorylation of the IGF 1 receptor are the same as the ligand induced autophosphorylation sites and that the Src kinase can catalyze these phosphorylations directly . 3 ) We showed that cells cultured from mice in which the IGF 1 receptor has been knocked out by homologous recombination are defective for morphological transformation by src . ^^^ Thus , the Src kinase can substitute for the receptor kinase in phosphorylating and activating the IGF 1 receptor , and this receptor phosphorylation and activation are essential for transformation by src . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A lipophilic analogue of peptide HC , stearyl peptide HC , added to intact CHO / HIRc cells enhanced significantly insulin stimulated insulin receptor autophosphorylation while having no effect on ligand stimulated receptor phosphorylation in CHO cells overexpressing either the IGF 1 receptor or epidermal growth factor receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 binding and IGF 1 receptor mRNA concentrations in porcine granulosa cells were not inhibited by TNFalpha . ^^^ Transient transfection studies done in mouse fibroblasts overexpressing the IGF 1 receptor ( NWTb 3 ) with the porcine IGFRE ( three repeats ) in an SV40 / luciferase construct also showed TNFalpha inhibited IGF 1 stimulated reporter gene expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In both breeds of goat , specific 125I IGF 1 binding was localised over the inner and outer root sheath , the matrix , the germinal matrix , the dermal papilla and the sebaceous glands and satisfied the basic kinetic criteria considered to be representative of a specific IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ras proteins mediate induction of uncoupling protein , IGF 1 , and IGF 1 receptor in rat fetal brown adipocyte cell lines . ^^^ Additionally , the role of Ras proteins on IGF 1 and IGF 1 receptor expression was studied . ^^^ Expression of the transfected ras oncogene also induced IGF 1 and IGF 1 receptor mRNAs , whereas expression of SV40LTag did not increase them . ^^^ These results indicate that Ras proteins mediate the IGF 1 induced effect on UCP expression and play a role in the expression of IGF 1 and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated whether chondrocyte PG synthetic activity correlates with the presence of chondrocyte IGF 1 receptor in the surface , middle and deeper zones of normal human articular cartilage and in cartilage known to display a shift in chondrocyte metabolism , i . e . cultured cartilage or osteoarthritic ( OA ) cartilage . ^^^ We examined chondrocyte PG synthesis by in situ autoradiography of incorporated [ 35S ] sulphate and chondrocyte IGF 1 receptor localization by immunohistochemistry , followed by confocal laser scanning microscopical ( CLSM ) analysis in the same cartilage samples . ^^^ In normal cartilage , both the amount of chondrocyte PG synthesis and the level of chondrocyte IGF 1 receptor localization are at low levels in the surface zone chondrocytes , but both are high in middle and deeper zone chondrocytes . ^^^ Furthermore , after culture , the increase in chondrocyte PG synthesis in the surface layer coincides with increase in IGF 1 receptor expression . ^^^ However , in mild OA particularly high levels of chondrocyte synthetic activity were found in the upper cartilage layer , whereas IGF 1 receptor expression was low in this layer , suggesting that factors other than IGF 1 are involved . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our results suggest that activation of both the IGF 1 receptor and the alpha5beta1 integrin is required for IGF 1 to stimulate wound healing . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The affinity of 4 Gly IGF 1 for the IGF 1 receptor was approximately 100 fold lower than that of wild type IGF 1 and the affinity for the insulin receptor was approximately 10 fold lower . ^^^ Not only does the C region of IGF 1 contribute directly to the free energy of binding to the IGF 1 receptor , but also the absence of flexibility in this region eliminates binding altogether . ^^^ As postulated for the binding of insulin to its own receptor , it is proposed that binding of IGF 1 to the IGF 1 receptor also involves a conformational change in which the C terminal B region residues detach from the body of the molecule to expose the underlying A region residues . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There was a substantially decreased level of IGF 1 receptor messenger ribonucleic acid in the Pygmy cells with a normal messenger ribonucleic acid half life . ^^^ These results indicate decreased IGF 1 receptor gene transcription and IGF 1 receptor signaling as the primary variation in the Pygmy cell lines . ^^^ The findings point to the IGF 1 receptor as the locus governing short stature in the African Pygmy and suggest that human stature may be genetically controlled by expression of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To study the interaction between insulin receptor ( IR ) and insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) tyrosine kinases , we examined IGF 1 action in Rat 1 cells expressing a naturally occurring tyrosine kinase deficient mutant IR ( Asp 1048 IR ) . ^^^ These results suggest that the Asp 1048 IR causes a dominant negative effect on IGF IR in transmitting signals to Shc and MAP kinase activation , which leads to decreased IGF 1 stimulated DNA synthesis , and that the kinase defective insulin receptor does not affect IGF 1 stimulated IRS 1 phosphorylation , which leads to the normal IGF 1 stimulated glycogen synthesis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An IGF 1 receptor lacking a functional ATP binding site provided no protection from apoptosis . ^^^ In the C terminus of the IGF 1 receptor , two mutations , one at tyrosine 1251 and one which replaced residues histidine 1293 and lysine 1294 , abolished the antiapoptotic function , whereas mutation of the four serines at 1280 to 1283 did not . ^^^ These studies demonstrate that the domains of the IGF 1 receptor required for its antiapoptotic function are distinct from those required for its proliferation or transformation functions and suggest that domains of the receptor required for inhibition of apoptosis are necessary but not sufficient for transformation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , the anti IGF IR monoclonal antibody ( mAb ; alpha IR 3 ) inhibited the DNA synthesis caused by 10 ng / ml exogenous IGF 1 ( 67 + / 6 % ) , IGF 2 ( 72 + / 8 % ) , and des IGF 1 ( 82 + / 9 % ) . ^^^ In the absence of exogenous IGF 1 , the mAb directed against the IGF IR significantly suppressed basal DNA synthesis of HL 60 promyeloid ( 72 + / 5 % ) and U 937 monocytic ( 39 + / 7 % ) cells , but did not affect DNA synthesis of KG 1 myeloblasts ( 8 + / 1 % ) compared to an isotype matched control mAb . ^^^ As the alpha IR 3 mAb inhibits DNA synthesis in the presence and absence of exogenous IGF 1 on receptor bearing cells , but not IGF IR negative cells , these data demonstrate that both endocrine and autocrine IGF 1 are potent growth factors in human myeloid cells where expression of the surface receptor , rather than the ligand , is the critical control element . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptors ( IR ) and IGF 1 receptors ( IGF IR ) have been shown to form hybrid receptors in tissues coexpressing both molecules . ^^^ Hybrids were quantified as the fraction of 125I IGF 1 binding immunoadsorbed with MA 20 and expressed as percentage of total IGF IR ( type I+hybrids ) immobilized with alpha IGF IR PA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Direct interaction of effector proteins such as the p 85 regulatory subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) , SYP ( SH 2 domain containing tyrosine phosphatase ) and GAP ( Ras GTPase activating protein ) with the insulin receptor ( IR ) and insulin like growth factor 1 ( IGF 1 ) type 1 receptor ( IGF 1R ) has been reported in some studies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 , IGF 1 receptor and IGF binding proteins 1 , 2 , 3 , 4 and 5 in human atherectomy specimens . ^^^ IGF 1 receptor , and five IGF binding proteins ( IGFBPs ) , IGFBP 1 , IGFBP 2 , IGFBP 3 , IGFBP 4 , and IGFBP 5 in smooth muscle cells ( SMCs ) using colloidal gold immunocytochemistry . ^^^ IGF 1 receptor localized on sSMCs and their processes and colocalized with IGF 1 . ^^^ Although morphometric analysis of IGF 1 and IGF 1 receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed comparable levels of IGF 1 ( 3 . 2 + / 1 . 0 and 2 . 9 + / 0 . 9 , respectively ) . ^^^ IGF 1 receptor was significantly higher in de novo lesions as compared to restenotic lesions ( 10 . 7 + / 2 . 5 and 4 . 2 + / 1 . 3 , P < 0 . 05 , respectively ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated signal transduction through IGF 1 receptor in comparison with epidermal growth factor ( EGF ) receptor in early passages of cultured skin fibroblasts from a normal subject and a patient with leprechaunism whose insulin receptor tyrosine kinase was almost nonexistent . ^^^ Signal transduction pathways following IGF 1 receptor or EGF receptor activation were indistinguishable between the normal subject and the patient . ^^^ Our results strongly suggest that in human skin fibroblasts , which represent a more physiological cell culture : 1 ) IRS 1 , rather than Shc , is the major tyrosine phosphorylated protein binding GRB 2 in initial phase of IGF 1 signaling ; 2 ) mitogenic potency of receptor tyrosine kinases such as IGF 1 receptor and EGF receptor may not be determined solely by the amount of Shc GRB 2 complex or the activity of MAP kinase ; and 3 ) in contrast to previous reports , IGF 1 and EGF receptor signalings are not defective in leprechaunism . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Before the appearance of apoptotic melanoma cells , assayed by gel electrophoretic detection of oligonucleosomally fragmented DNA , the binding of insulin like growth factor 1 ( IGF 1 ) to the cells had become drastically decreased , which in turn was found to be due to down regulation of IGF 1 receptor proteins at the cell surface . ^^^ Taken together , our data suggest strongly that N linked glycosylation plays an important role in maintenance of viability of melanoma cells through regulating the translocation of IGF 1 receptor to the cell surface . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although TAM can increase IGFBP 3 expression in MCF 7 cells , and this binding protein has been shown to be able to inhibit IGF action , TAM had no effect on IGF 1 stimulated tyrosine phosphorylation of IGF 1 receptor or the downstream signaling molecule , insulin receptor substrate 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , ASPB 10 was twofold more potent than insulin in stimulating insulin receptor autophosphorylation but significantly more potent in stimulating IGF 1 receptor autophosphorylation in both cell lines . ^^^ This increased mitogenic effect of ASPB 10 was significantly inhibited ( but not abolished ) when cells were cultured in the presence of alpha IR 3 , a monoclonal antibody to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have investigated the role of IGF IR number in IGF 1 mediated mitogenesis and transformation of mouse embryo fibroblasts . ^^^ The IGF 1 receptor in mitogenesis and transformation of mouse embryo cells : role of receptor number . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , the IGF 1 receptor on PV progenitor cells exhibits increased basal phosphorylation and a hypersensitivity and hyperresponsiveness to IGF 1 with respect to tyrosine phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNA was first reverse transcribed with an oligomer bearing a complementary sequence specific for the mRNA at its 3 ' end , and a sequence complementary to an intervening intron of the IGF 1 receptor gene at the 5 ' end . ^^^ No difference was noted in IGF 1 receptor expression between neoplastic and normal colonic mucosa . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have investigated the molecular mechanism by which two growth factors , insulin like growth factor 1 ( IGF 1 ) and basic fibroblast growth factor ( bFGF ) regulate IGF IR gene expression . bFGF increases the endogenous IGF IR mRNA levels and IGF IR promoter activity . ^^^ In contrast , IGF 1 decreases the IGF IR mRNA levels . ^^^ IGF 1 down regulates IGF IR transcriptional activity as deduced from experiments in which the levels of pre mRNA and mRNA were measured . ^^^ While these results strongly suggest an effect of IGF 1 on IGF IR transcriptional activity , no specific IGF 1 response element was demonstrated in the 5 ' untranslated region or 5 ' flanking region studied . ^^^ Thus , bFGF and IGF 1 have differential effects on IGF IR gene transcription , with the IGF 1 response region as yet unidentified . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Plasmon resonance spectroscopy experiments revealed that all the high Mr isoforms and mature 7 . 5 kDa IGF 2 bound to immobilized recombinant soluble human IGF 1 receptor , recombinant human IGF binding protein 1 , and sIGF II / MPR with similar kinetics . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that the CD 20 channel is regulated by the IGF 1 receptor by a mechanism involving pertussis toxin sensitive G protein . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Maximal phosphorylation of FAK and paxillin was observed 15 30 min after the addition of 10 nM IGF 1 , whereas maximal IGF 1 receptor phosphorylation occurred within 5 min . ^^^ FAK , paxillin , and IGF 1 receptor tyrosine phosphorylation had similar concentration response curves and were inhibited by the receptor blocking antibody alphaIR 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Antiapoptotic signalling by the IGF 1 receptor depended on receptor kinase activity , as cells overexpressing kinase defective receptor mutants could not be protected by IGF 1 . ^^^ The antiapoptotic capacity of the IGF 1 receptor was not shared by other growth factors tested , including epidermal growth factor ( EGF ) and thrombin , although the cells expressed functional receptors for all the agonists . ^^^ We conclude that the endogenous IGF 1 receptor has a specific antiapoptotic signalling capacity , that overexpression of other tyrosine kinases can allow them also to be antiapoptotic , and that activation of PI 3 kinase and Akt is sufficient for antiapoptotic signalling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this paper , we examined whether this age deficit can be attributed to an alteration in the expression and binding kinetics of IGF 1 receptor . ^^^ We showed that the levels of IGF 1 receptor mRNA in cells , estimated by RT PCR , were not significantly altered with age . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , it appears that signaling from the IGF 1 receptor utilizes two distinct pathways leading either to proliferation or differentiation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thyroid hormone exerts profound effects on the insulin like growth factors ( IGFs ) / IGF factor 1 receptor ( IGF IR ) system through its action on the production of IGF 1 peptide and IGF binding proteins . ^^^ In the heart , this regulation occurs at a pretranslational level , indicated by the fact that parallel changes in the number of membrane IGF 1 receptors and IGF IR transcripts were observed , whereas in lung , no effect of thyroid hormone was noted in the amount of IGF IR transcripts , suggesting a translational or posttranslational control . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) plays a potential functional role in cerebellar development in the rat , as indicated by its spatio temporally coordinated expression with the IGF 1 receptor ( IGFR 1 ) , IGF binding protein ( IGFBP ) 2 and 5 during the postnatal critical growth period . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Autoradiography of the 6 % gel showed two specific bands at 115 kD and 240 kD , consistent with monomeric and dimeric forms of the IGF 1 receptor , which were inhibited by excess insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report here that overexpression of the IGF IR did not modify sensitivity of cells to IGF 1 ; however , responsiveness to the ligand was moderately enhanced in most of the MCF 7 / IGF IR clones ( measured by [ 3H ] thymidine incorporation into DNA ) . ^^^ All MCF 7 / IGF IR clones responded to the synergistic action of 1 nM estradiol ( E 2 ) and small amounts of IGF 1 ( up to 0 . 8 ng / ml ) . ^^^ Exposure of cells to higher concentrations of IGF 1 abolished estrogen requirements for stimulation of DNA synthesis in all MCF 7 / IGF IR clones , but not in the parental cells . ^^^ In both MCF 7 and MCF 7 / IGF IR cells , IGF 1 stimulated aggregation , whereas an anti E cadherin antibody blocked cell cell adhesion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Lastly , preincubation of the cells with IGF 1 receptor antibodies diminished the IGF 1 induced Ca2+ spike and totally abolished the Ca2+ influx , but did not modify the effect of IGF 2 . ^^^ These results suggest that IGF 1 action on Ca2+ influx involves the IGF 1 receptor , while part of IGF 1 and all of IGF 2 Ca2+ mobilization do not implicate this receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Previously , we found that , in the myeloproliferative disorder polycythemia vera ( PV ) , circulating erythroid progenitor cells were hypersensitive to insulin like growth factor 1 ( IGF 1 ) , an effect shown to occur through the IGF 1 receptor . ^^^ Also , in cells of PV patients , the IGF 1 receptor was hyperphosphorylated on tyrosine residues under basal conditions , and its tyrosine phosphorylation in response to exogenous IGF 1 was strongly augmented . ^^^ If IGFBP 1 were inhibitory , it might suggest a compensatory mechanism in which a hyperphosphorylated IGF 1 receptor in PV might induce a negative modulator of IGF 1 action , in this case IGFBP 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVES : The objective was to study potential regulation of insulin like growth factor 1 ( IGF 1 ) , its binding proteins , and the IGF 1 receptor by reactive oxygen species in vascular smooth muscle cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Competition binding experiments showed a slightly higher affinity of HOE 901 for the IGF 1 receptor when compared to regular human insulin with IC 50 ( half inhibitory concentration ) values of 70 and 101 nM , respectively . ^^^ We concluded that the IGF 1 receptor mediated growth promoting activity of HOE 901 in muscle cells and the maximal metabolic activity of this analogue are not different from those of native human insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of IGF 1 are mainly mediated through the IGF 1 receptor ( IGF IR ) and modulated by six specific IGF binding proteins ( IGFBPs ) . ^^^ We investigated the gene expression of IGF 1 , IGF IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short term ( 7 day ) STZ diabetic , insulin treated euglycaemic and normal rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The adapter protein Grb 10 associates preferentially with the insulin receptor as compared with the IGF 1 receptor in mouse fibroblasts . ^^^ Receptor deficient R cells ( fibroblasts from mice with homologous disruption of the IGF 1 receptor gene ) and transfected R cells expressing either insulin receptors ( R IR cells ) or IGF 1 receptors ( R+ cells ) were used to investigate the specificity of Grb 10 interaction with the two related receptors . ^^^ Under the same conditions , Grb 10 was essentially undetectable in IGF 1 receptor immunoprecipitates from stimulated R+ cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since IGF 1 action is mediated through its receptor and as its bioavailability is regulated by IGF binding proteins ( IGFBP ) , we postulated that changes in IGF 1 receptor binding or IGFBP production may favor a role for IGF 1 in diabetic renal growth when kidney IGF 1 levels have returned to normal . ^^^ In diabetic cortex and medulla , growth hormone receptor mRNA levels and IGF 1 and IGF 1 receptor mRNA and protein product levels were unchanged . ^^^ However , the lack of change in IGF 1 , IGF 1 receptor and growth hormone receptor gene expression and protein products after one week of diabetes argues against a role for IGF 1 in sustaining diabetic renal growth beyond the initial growth phase . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The dose response characteristics of the fibre differentiation response suggest that mediation occurs mainly through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Control of insulin like growth factor ( IGF ) action by regulation of IGF 1 receptor expression . ^^^ Most of the actions of both IGF 1 and IGF 2 are mediated by their activation of the IGF 1 receptor , a transmembrane tyrosine kinase that is structurally and functionally related to the insulin receptor . ^^^ Control of the IGF 1 receptor number at the cell surface is an important level at which IGF action can be regulated . ^^^ Cell surface receptor number , in turn , is principally determined by the level of expression of the IGF 1 receptor gene . ^^^ An important transcriptional regulatory factor that appears to be responsible for controlling IGF 1 receptor gene expression is the product of the WT 1 Wilms tumor suppressor gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor binding , autophosphorylation , and kinase activity in kidney and muscle of acutely uremic rats . ^^^ Following acute tubular necrosis ( ATN ) , kidney plasma membrane insulin like growth factor 1 ( IGF 1 ) receptor number increases markedly , although IGF 1 receptor mRNA levels do not change . ^^^ Since these early steps of IGF 1 receptor signaling are intact early in acute uremia , it is likely that at this time in the course of the disease the increase in receptor number will heighten the sensitivity to IGF 1 and may thus favor its participation in renal repair . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Taken together with the fact that pancreatic beta cells express little or no insulin receptor but large amounts of IGF 1 receptor , these data strongly suggest a new regulatory feedback loop model for the control of insulin secretion . ^^^ In this model , increased insulin secretion in vivo will stimulate IGF 1 synthesis by the liver , and the secreted IGF 1 in turn feedback inhibits insulin secretion from the beta cells through an IGF 1 receptor mediated pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Structural changes in insulin like growth factor ( IGF ) 1 mutant proteins affecting binding kinetic rates to IGF binding protein 1 and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , we investigated the IGF 1 receptor concentration and binding characteristics in benign and carcinomatous adrenocortical tumors . ^^^ Membrane preparations of 14 normal adrenocortical glands showed a mean specific 125I IGF 1 binding ( SB ) of 5 . 0 + / 0 . 5 % and a competition by unlabeled ligands which is characteristic of the IGF 1 receptor . ^^^ Affinity cross linking experiments with normal and tumorous adrenocortical tissue displayed a band at an apparent molecular mass of 135 kDa , corresponding to the size of the normal alpha subunit of the IGF 1 receptor . ^^^ When 125I IGF 1 binding in adrenocortical hyperplasias ( SB 4 . 1 + / 0 . 4 % , RC 19 . 6 + / 2 . 0 nmol / kg protein , Kd 0 . 19 + / 0 . 04 nmol / l , n = 4 ) and adenomas ( SB 4 . 0 + / 1 . 1 % , RC 17 . 5 + / 3 . 1 nmol / kg protein , Kd 0 . 21 + / 0 . 04 nmol / l , n = 4 ) was compared with the 125I IGF 1 binding in normal adrenocortical tissue , similar IGF 1 receptor concentration and binding kinetics were found . ^^^ In contrast , three out of four hormonally active adrenocortical carcinomas showed a strongly elevated specific 125I IGF 1 binding with a 3 to 4 fold increase in IGF 1 receptor concentration , as compared with normal adrenocortical tissue . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using highly purified mature osteoclasts , the IGF 1 receptor was characterized on the molecular level according to its size and its affinity and number per osteoclast by isolation of the receptor ligand complex and by binding studies , respectively , and on the cellular level according to the response of mature osteoclasts to IGF 1 stimulation . ^^^ In situ hybridization and autoradiography experiments showed that osteoclasts express IGF 1 receptor mRNA and IGF 1 binding sites . ^^^ Chemical cross linking of 125I IGF 1 bound to the purified mature osteoclasts and subsequent sodium dodecyl sulfide polyacrylamide gel electrophoresis revealed the specific binding of 125I IGF 1 in complexes with molecular masses of 130 and 230 RD consistent with binding to the IGF 1 receptor . ^^^ Searching for a role of the IGF 1 receptor in mature osteoclasts , we found no significant influence of IGF 1 on the levels of the proform of matrix metaloproteinase 9 and tartrate resistant acid phosphatase . ^^^ These data show that functionally active IGF 1 receptor is present in mature osteoclasts . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , we have demonstrated the effectiveness of clinical administration of insulin like growth factor 1 ( IGF 1 ) in this patient and in vitro analysis of the patient ' s skin fibroblasts , suggesting that IGF 1 can compensate for insulin action via the IGF 1 receptor in a patient almost lacking functional insulin receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To assess the autocrine function of insulin like growth factor 2 ( IGF 2 ) in the balance of proliferation and differentiation in HT 29 D4 human colonic cancer cells , we studied the expression of IGF 1 receptors ( IGF IR ) and insulin receptors ( IR ) in relation to the state of cell differentiation . ^^^ HR were evidenced through 1 ) inhibition of IGF 1 binding by the B 6 anti IR antibody and 2 ) immunoprecipitation with the alpha IR 3 anti IGF IR antibody , which revealed an additional 95 kDa IR beta subunit that disappeared when the heterotetrameric receptor was dissociated by disulfide reduction into alphabeta heterodimers before immunoprecipitation . ^^^ Like IGF IR , HR had a high affinity for IGF 1 ( Kd , approximately 1 . 5 nM ) , but did not bind insulin significantly ; the latter interacted with the native IR only ( Kd , approximately 4 nM ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The homolog IGF 2 was also effective although less potent than IGF 1 suggesting the involvement of a typical IGF 1 receptor in the observed neuroprotective effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Gastrocnemius muscles were analyzed for IGF 1 receptor mRNA levels , IGF 1 receptor number , and IGF 1 receptor binding capacities and affinity constants . ^^^ These animals demonstrated declines in IGF 1 receptor protein . ^^^ After acute exercise , IGF 1 receptor mRNA was elevated , IGF 1 receptor protein levels were unaffected , and rates of protein synthesis were stimulated by IGF 1 in the 12 and 24 mo old animals . ^^^ Acute exercise significantly increased IGF 1 receptor binding capacity and affinity constants in the 24 but not the 12 mo old animals . ^^^ We conclude that acute exercise can restore the action of IGF 1 in aged muscle , potentially by increasing the IGF 1 receptor binding capacity and affinity or as a result of factors downstream of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Equilibrium binding experiments using ( 125 ) 1 labeled IGF 1 showed the presence of an IGF 1 receptor with a dissociation constant of 1 . 96 nM and a maximal binding constant of 53 , 000 receptors / cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding experiments to intact MME L 1 cells suggests that this difference most likely results from a correspondingly lower affinity for IGF 1 receptor in these cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Each of these death mechanisms could be blocked by activation of different pathways , such as raising cAMP production or stimulation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
While antioestrogens such as tamoxifen and droloxifene reduce the expression of IGF IR in vitro and suppress plasma levels of IGF 1 but elevate IGF binding protein 1 in vivo , megestrol acetate may reduce the delivery of IGFs to the tissues by inhibition of IGFBP 3 protease activity . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This increased adhesion was attenuated by pretreatment with IGF 1 receptor antibody , as well as with genistein and herbimycin A , which are potent and selective tyrosine kinase inhibitors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor phosphorylation and coimmunoprecipitation of phosphatidylinositol 3 kinase by antiphosphotyrosine antibodies was also observed in liver , and was associated with a decrease in mRNA levels of the key gluconeogenetic enzyme phosphoenolpyruvate carboxykinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tumor growth , serum , liver , and tumor IGF levels and IGF 1 receptor concentrations in Caki 1 cell membranes were measured . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Previously we and others have demonstrated that substitution of both tyrosines at positions 1250 and 1251 in the carboxy terminal region of the human IGF 1 receptor has relatively small effects on receptor and endogenous substrate phosphorylation but completely abrogated the ability of these cells to form tumors in nude mice or proliferate in response to IGF 1 in culture . ^^^ To further characterize the role of these tyrosines in IGF 1 receptor function , we have used three distinct approaches to examine the ras / MAP kinase pathway in IGF 1 induced mitogenesis and tumorigenesis in NIH 3T3 cells overexpressing wild type and mutated IGF 1 receptors : 1 ) tyrosine phosphorylation of the MAP kinases Erk 1 and 2 ; 2 ) , mobility shifts indicative of MAP kinase phosphorylation ; and 3 ) in vitro MAP kinase activation . ^^^ We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C terminal domain of the IGF 1 receptor include pathways other than the MAP kinase and PI 3 kinase pathways . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Exposure of COC to an IGF 1 receptor ( IGF 1R ) neutralizing antibody ( Ab ) for 90 min before addition of FSH and FBS dose dependently inhibited cumulus expansion , with maximal inhibition at 10 microg / ml ( 1 + / 1 . 0 % vs . 68 + / 1 . 1 % control ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Early bovine embryos also express IGF 1 , IGF 2 , IGF 1 receptor , IGF 2 receptor , and insulin receptor mRNAs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When the calcium permeable cation channel CD 20 is expressed in Balb / c 3T3 cells , it is activated by insulin like growth factor 1 ( IGF 1 ) via the IGF 1 receptor ( Kanzaki , M . , Nie , L . , Shibata , H . , and Kojima , 1 . ( 1997 ) J . ^^^ These findings indicate that the CD 20 channel expressed in Balb / c 3T3 cells is activated by the IGF 1 receptor via the alpha subunits of heterotrimeric G proteins . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because their affinity constants are between two and 50 fold greater than the IGF 1 receptor , they control the distribution of the IGFs among soluble IGFBPs in interstitial fluids , IGFBPs bound to cell surfaces or extracellular matrix ( ECM ) and cell surface receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Light microscopic study of insulin like growth factor 2 ( IGF 2 ) and insulin like growth factor 1 receptor ( IGF 1 R ) in myopathy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
With this approach , we confirm the previously characterized interaction between Grb 2 and the EGF receptor , and we identify novel partners of the IGF 1 receptor and of the JAK proteins . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This effect was completely inhibited by preincubation with 0 . 5 microM okadaic acid , suggesting that the IGF 1 receptor transduction pathway can act on the phosphorylation state of the chloride channel through a serine threonine protein phosphatase . 6 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since insulin like growth factor 1 ( IGF 1 ) and insulin receptors are structurally homologous , we investigated whether pp 120 is also a substrate of the IGF 1 receptor tyrosine kinase . ^^^ IGF 1 receptor failed to phosphorylate pp 120 in response to IGF 1 in stably transfected NIH 3T3 fibroblasts . ^^^ However , replacement of the C terminal domain of the beta subunit of the IGF 1 receptor with the corresponding fragment in the insulin receptor restored ligand stimulated pp 120 phosphorylation , suggesting that this domain plays a regulatory role in pp 120 phosphorylation . ^^^ Since pp 120 is the first identified substrate specific for the insulin vis  vis the IGF 1 receptor tyrosine kinase , the pp 120 signaling pathway may constitute a novel mechanism for the distinct cellular effects of insulin and IGF 1 , the former being principally involved in metabolism , and the latter in mitogenesis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dietary protein restriction reduced plasma concentrations of IGF 1 and IGF binding proteins ( IGFBPs ) and hepatic IGF 1 mRNA content , while increasing colonic IGF 1 receptor mRNA . ^^^ Dietary protein repletion resulted in a decrease in colonic IGF 1 receptor mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of insulin like growth factor 1 ( IGF 1 ; 100 ng / ml ) and / or overexpression of the IGF 1 receptor ( IGF 1R ) attenuated the cytotoxicity of DMF . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although 5 src is a more potent inducer of tyrosine phosphorylation than c src 527 , the extent of phosphorylation of either insulin receptor substrate 1 or Shc , two of the major substrates of the IGF 1 receptor , does not seem sufficiently different to explain the qualitative difference in soft agar growth . 5 src , however , is considerably more efficient than c src 527 in its ability to tyrosyl phosphorylate , in R cells , the focal adhesion kinase , Stat 1 , and p130cas . ^^^ These results indicate that 5 src , but not c src 527 , can bypass the requirement for a functional IGF 1 receptor in the full transformation of mouse embryo fibroblasts and suggest that qualitative and quantitative differences between the two oncogenes can be used to identify some of the signals relevant to the mechanism ( s ) of transformation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The specificity of the IGF response was confirmed using an IGF 1 receptor Ab , and additional studies demonstrated that IGF responsiveness did not result from induction of autocrine IL 6 expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 stimulated autophosphorylation of the IGF IR and tyrosine phosphorylation of IRS 1 and SHC , known substrates in the IGF IR signal transduction pathway , were studied . ^^^ IGF 1 stimulation of Crk 2 phosphorylation , a novel substrate of the IGF IR , was similar in cells expressing mutated and wild type IGF IRs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we have used ribonuclease protection assay , in situ hybridization , and immunohistochemistry to demonstrate that IGF 1 , IGFBPs , and IGF 1R expression alters in response to a penetrating CNS injury . ^^^ Within penetrant cerebral wounds in the acute phase of the response ( 1 7 days post lesion ; dpl ) , increased levels of IGF 1 , IGFBP 1 , 2 , 3 , 6 , and IGF 1R protein were localized to injury responsive astrocytes , neurons and cells of the monocyte lineage . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptors ( IR ) and type 1 IGF receptors ( IGF IR ) have been shown to form insulin / IGF 1 hybrid receptors in tissues expressing both molecules . ^^^ Results demonstrated that the proportion of total IGF IR assembled as hybrids varied between 40 and 60 % , thus indicating that hybrid receptors account for a large fraction of total IGF 1 binding in human tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The cytostatic activity of tamoxifen ( Tam ) , a nonsteroidal antiestrogen , is partially mediated through interference with IGF 1 R dependent proliferation , yet the effects of Tam on IGF IR intracellular signaling have never been elucidated . ^^^ In MCF 7 and MCF 7 / IGF IR cells , growth inhibition by Tam was associated with the reduced tyrosine phosphorylation of the IGF IR in the presence of IGF 1 ; however , the basal level of the IGF IR remained unaffected . ^^^ In summary , this work provides the first evidence that in MCF 7 cells , cytostatic effects of Tam are associated with the modulation of IGF IR signaling , specifically with : ( a ) down regulation of IGF 1 induced tyrosine phosphorylation of the IGF IR ; ( b ) inhibition of IRS 1 / phosphatidylinositol 3 ' kinase signaling ; and ( c ) up regulation of SHC tyrosine phosphorylation and increased SHC / GRB2 binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The type 1 IGF receptor ( IGF 1R ) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation , consistent with the role of its ligands ( IGF 1 and IGF 2 ) as important mitogenic factors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These studies revealed that a number of amino acids critical for insulin binding are conserved in the IGF 1 receptor , suggesting that they may play a role in ligand binding . ^^^ However , in contrast , the relative affinity of des ( 25 30 ) [ PheB 25 alpha carboxamide ] insulin for these IGF 1 receptor mutants is reduced only 4 and 50 fold , respectively . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
No effects were seen on LV weight , cardiac insulin like growth factor ( IGF ) 1 , IGF 1 receptor and GH receptor mRNA content . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Two different beta subunits of IGF 1 receptor were detected , and their autophosphorylation was followed by increases in the phosphotyrosine content of extracellular signal regulated kinases ( ERKs ) , insulin receptor substrate 1 , phospholipase C gamma 1 , and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When quiescent cultures of bovine fibroblasts were stimulated with 10 nM IGF 1 and total cell lysates immunoblotted with anti phosphotyrosine antibody , we observed a band at approximately 97 kDa , representing the beta subunit of the IGF 1 receptor , and a predominant tyrosyl phosphorylated species migrating as a broad band between 170 and 190 kDa . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , IGF 1 receptor tyrosine kinase activity was not affected by forskolin , suggesting that the increase in IRS 1 tyrosine phosphorylation was not the result of an increase in its activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The aim of the present study was to determine which event ( s ) of the transduction pathway from IGF 1 receptor to maturation promoting factor ( MPF ) activation is deficient in the small , vitellogenic , oocytes to explain their inability to undergo germinal vesicle breakdown ( GVB ) after insulin treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the other hand , it contains betagc , which is a novel variant of the beta subunit of the IGF 1 receptor , which is highly enriched in growth cone membranes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The cells showed no specific binding of 125I IGF 1 and furthermore , no IGF 1 receptor mRNA was detected by RNAse protection assay in the LB cells , in contrast with mouse brain and thymus . ^^^ The LB cell line is therefore an ideal model with which to investigate insulin mitogenic signalling without interference from the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Modifications in the B 10 and B 26 30 regions of the B chain of human insulin alter affinity for the human IGF 1 receptor more than for the insulin receptor . ^^^ Substitution with basic residues in the B 28 position increased the relative affinity to the IGF 1 receptor approximately 1 . 5 2 fold ( ArgB28ProB29 > OrnB28ProB29 = LysB28ProB29 ) . ^^^ Substitution with acidic residues reduced relative affinity for the IGF 1 receptor approximately 2 fold ( CyaB28ProB29 = GluB28ProB29 > AspB28ProB29 ) . ^^^ AspB10LysB28ProB29 HI ) showed an additional 2 fold selective increase in affinity for the IGF 1 receptor , suggesting that these two effects are additive . ^^^ Addition of Arg residues at B 31 32 , on the backbone of either HI or AspB 10 HI , increased affinity for the IGF 1 receptor 10 and 28 fold , respectively , compared to HI , confirming the significance of enhanced positive charge at the C terminal end of the insulin B chain in increasing selectivity for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA in bupivacaine injected muscle of old rats was elevated significantly higher than injected muscle of young and adult rats at recovery day 5 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Conceivable mevalonate dependent mechanisms involved in growth control are farnesylation of Ras proteins , regulation of c myc expression , and N linked glycosylation of the IGF 1 receptor . ^^^ The order and magnitude of the decreased IGF 1 receptor glycosylation , which was followed by a decreased expression of IGF 1 receptors at the cell membrane , correlated well with the inhibition of DNA synthesis . ^^^ We investigated whether dolichol , and in particular dolichyl phosphate , through its participation in N linked glycosylation , act as regulators of IGF 1 receptor expression . ^^^ Taken together , our results provide direct evidence for an important role of dolichyl phosphate as a regulator of cell growth through limiting N linked glycosylation of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To improve cellular uptake of a PNA sequence , it was conjugated to a D amino acid analog of insulin like growth factor 1 ( IGF 1 ) , which binds selectively to the cell surface receptor for insulin like growth factor 1 ( IGF1R ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In SH SY5Y human neuroblastoma cells , treatment with IGF 1 induced concentration and time dependent tyrosine phosphorylation of the type 1 IGF receptor ( IGF IR ) and extracellular signal regulated protein kinases ( ERK ) 1 and 2 . ^^^ These effects of IGF 1 were blocked by a neutralizing antibody against IGF IR . ^^^ Also , the concentration dependence of IGF 1 stimulated IGF IR and ERK tyrosine phosphorylation paralleled that of IGF 1 mediated neurite outgrowth . ^^^ Whereas PD 98059 had no effect on IGF IR phosphorylation , PD 98059 reduced IGF 1 mediated ERK tyrosine phosphorylation and ERK phosphorylation of the substrate Elk 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Measurements of phosphatidylinositol 3 kinase activity in microinjected cells support the hypothesis that the IGF 1 receptor stimulates glucose transport by a Ras dependent activation of phosphatidylinositol 3 kinase , whereas the G protein coupled LPA receptor controls this response by a pathway that involves Rho dependent activation of a distinct phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Genetic analyses of dwarfing phenotypes resulting from targeted mutagenesis of the genes encoding the insulin like growth factors ( IGF 1 and IGF 2 ) and their cognate type 1 IGF receptor ( IGF1R ) have demonstrated that this signaling system is a major determinant of mouse embryonic growth . ^^^ Of the two IGF ligands , IGF 1 interacts exclusively with IGF1R , whereas IGF 2 recognizes an additional receptor ( XR ) , because the growth retardation of embryos lacking both IGR1R and IGF 2 ( 30 % of normal birthweight ) is more severe than that manifested in either class of single Igf1r or Igf 2 null mutants ( 45 and 60 % of normal , respectively ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In conclusion , the growth promoting effect of IGF 1 on adult myocytes is regulated by the density of IGF 1R , which conditions the activation of the replicatory machinery of the cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These findings suggest that the inhibition of IGF 1 stimulated DNA synthesis in cumulus cells is a consequence of induction of cumulus cell differentiation ( mucification ) by FSH and EGF rather than through competition between IGF 1 receptor and IGFBP secretion induced by these agents . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Hence . recently reported changes in IGF 1 receptor messenger RNA levels in aged memory impaired rats are apparently not reflected at the level of the translated protein . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This is consistent with an important role for TTF 2 as a mediator of the transcriptional activation of thyroid specific genes ( thyroglobulin and thyroperoxidase ) by TSH via cAMP and by insulin through the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that IGFBP 3 enhances apoptosis by reducing bioavailability of ligands for the IGF 1 receptor and suggest that modulation of IGFBP 3 expression by ICI contributes to apoptosis induced by this compound . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RhIGF 1 can reduce hyperglycaemia in patients with severe insulin resistance by direct effects mediated via the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To examine whether these differences relate to intrinsic signaling properties of the intracellular domains of their respective receptors , chimeric receptors were constructed using the extracellular domain of the neurotrophin 3 ( NT 3 ) receptor , TrkC , and the intracellular domain of either the insulin receptor or the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of the IGF 1 receptor mRNA in brain peaks at times of active cell development perinatally and remains detectable , albeit at lower levels , in the adult . ^^^ While both autoradiographic and in situ hybridization studies show a wide and specific distribution of IGF 1 receptor throughout the adult rat brain , nothing is yet known about its subcellular localization , a critical issue that will help clarify the biological role of this trophic factor in the adult brain . ^^^ The present study describes the subcellular localization of IGF 1 receptor immunoreactivity in the cerebellar cortex and the hypothalamic arcuate nucleus by using electron microscopic immunocytochemistry . ^^^ In the cerebellum , IGF 1 receptor immunoreactivity is present postsynaptically in the dendrites and soma of the Purkinje cell and presynaptically in axon terminals impinging upon the Purkinje cell soma , as well as in mossy fibre rosettes in the cerebellar glomeruli . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Invest . 71 : 657 662 , 1994 ) that ethanol in low concentrations inhibits the tyrosine autophosphorylation of the IGF 1 receptor ( IGF IR ) and IGF 1 mediated cell proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The activation of such growth factor receptors as the insulin like growth factor 1 receptor ( IGF 1 R ) , erbB type receptors ( erbB Rs ) and FGF receptors ( FGF Rs ) controls the phenotype of a model breast cancer cell line MCF 7 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockade of the IGF 1 receptor with a neutralizing antibody abrogated the VEGF increases in RPE cells . ^^^ The VEGF increases in RPE cells occurred primarily through enhanced transcription of the VEGF gene and via the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To examine the mechanism ( s ) by which this sensitization may occur , levels of mRNA encoding OP 1 receptor , IGF 1 receptor , and IGFBPs were measured . ^^^ IGF 1 receptor gene expression was not changed by OP 1 , IGF 1 , or a combination of both factors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In summary , ovarian derived GH N and PL A / B synthesis correlates well with the established local cascade of GHRH , GHRH receptor , GH receptor , IGF 1 , and IGF 1 receptor as a putative para / autocrine regulator of ovarian reproductive function . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : Insulin like growth factor 1 ( IGF 1 ) is a peptide growth factor whose biological effects are mediated through a specific receptor ( IGF IR ) . ^^^ IGF 1 and IGF IR are detected in both fetal and adult kidneys and have both metabolic and growth effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHOD OF STUDY : Thirty donated day 3 embryos were cultured in vitro for an additional 3 days to observe their developmental potential and were semiquantitatively analyzed for the expression of IGF 1 , IGF 2 , IGF IR , IGF IIR , and insulin R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptor / IGF 1 receptor hybrids are widely distributed in mammalian tissues : quantification of individual receptor species by selective immunoprecipitation and immunoblotting . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both human and rat mesangial cells grown on BSA AGE showed increased IGF 1 and total and bioactive TGF beta medium levels and enhanced IGF 1 , IGF 2 , and TGF beta 1 gene expression , compared with cells grown on BSA , whereas total IGFBP and IGFBP 3 medium content , IGF receptor density and affinity , and IGF 1 receptor transcripts were unchanged . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In 4 5 week placentae , IGF 1 and IGF 1 receptor were almost exclusively localized in cytotrophoblasts and IGF 1 augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL . ^^^ By contrast , in 6 12 week placentae , IGF 1 and IGF 1 receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF 1 stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of trophoblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To test this hypothesis , we stably transfected a GTPase deficient mutant human Galpha 13 , which is highly oncogenic when overexpressed in vitro , into R fibroblasts derived from IGF 1 receptor deficient mice . ^^^ Overexpression of the IGF 1 receptor enabled R cells to form colonies ( 27 colonies ) , and co transfection of the mutant Galpha 13 caused a further increase in colony formation ( 117 153 colonies ) in three of five clones analyzed . ^^^ These results demonstrate that Galpha 13 can induce cellular transformation through pathways apparently independent of the IGF 1 receptor and that activation of the IGF 1 receptor signaling pathways , although not essential for the transforming phenotype , enhances the effect of other pathways . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , proinsulin showed no significant interaction with the IGF 1 receptor , while a chimeric proinsulin containing the C peptide of IGF 1 had an intermediate interaction , consistent with its affinity for the IGF 1 receptor . ^^^ Using PCR based mutagenesis with proinsulin , we also identified a gain of function mutant ( proinsulin Leu 17 > Pro ) that allowed for a strong IGF 1 receptor interaction . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding affinities of insulin like growth factor 1 ( IGF 1 ) fusion proteins to IGF binding protein 1 and IGF 1 receptor are not correlated with mitogenic activity . ^^^
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Vitamin D derivatives were also demonstrated to reduce IGF 1 receptor expression in MCF 7 cells by Western analysis . ^^^ Our findings demonstrate that vitamin D derivatives limit responsiveness of MCF 7 cells to the mitogenic effects of IGF 1 , which may be mediated by reduction of IGF 1 receptor expression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , IGF 1 stimulates the mitogen activated protein kinase in GH 3 cells , showing that the components linking the IGF 1 receptor to Ras are also active . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , in liver , LD and TR , IGF 1 receptor mRNA levels were not different between pGH treated and control animals . ^^^ It can be concluded that ( 1 ) GH binding and IGF 1 receptor mRNA are not affected by GH in skeletal muscle , ( 2 ) GH influences GHR in a tissue specific manner and ( 3 ) hepatic GHR and GHBP levels are not co regulated . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , we characterized the distribution of IGF 1 and IGF 2 receptor sites and investigated the effects of both factors on endogenous acetylcholine ( ACh ) release in adult rat hippocampus . [ 125I ] IGF 1 receptor binding sites are recognized by IGF 1 > IGF 2 > insulin , whereas [ 125I ] IGF 2 binding was competed potently by IGF 2 > IGF 1 but not by insulin . ^^^ At the cellular level , IGF 1 receptor sites were primarily noted in the molecular layer of the dentate gyrus and the CA 2 CA3 subfields of the Ammon ' s horn whereas IGF 2 sites were localized predominantly in the pyramidal cell layer of the CA 1 CA3 subfields and in the granular cell layer of the dentate gyrus . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The 5 ' untranslated region of the IGF 1 receptor gene modulates reporter gene expression by both pre and post transcriptional mechanisms . ^^^ In order to examine the role that this region plays in regulating IGF 1 receptor expression , we isolated fragments of the human IGF 1 receptor 5 ' UTR and interposed them between the SV 40 early promoter and the chloramphenicol acetyl transferase reporter gene . ^^^ Fragments of the IGF 1 receptor gene 5 ' UTR were found to enhance reporter gene expression by increasing gene transcription . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In an attempt to determine how the changes in IGF 1 receptor number are regulated during development , we have compared [ 125I ] IGF 1 binding to membrane fractions with the concentration of IGF 1 receptor mRNA in rat liver and brain . ^^^ In fetal and regenerating liver increases similar to those observed for IGF 1 binding were observed in IGF 1 receptor mRNA concentrations . ^^^ In contrast to the liver , no significant changes in the concentration of IGF 1 receptor mRNA were observed in the developing brain when determined by hybridization solution , Northern blot or RNase protection analysis . ^^^ These findings suggest that in the liver , the IGF 1 receptor gene is regulated at pretranslational level during development and regeneration , while in brain it is preferentially regulated at translational or posttranslational level . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , Northern blotting experiments showed specific IGF 1 receptor and IGF II / M6P receptor gene expression in CaCo 2 cells . ^^^ An 11 kb band was visualized with a 614 bp PstI IGF 1 receptor probe on autoradiographs . ^^^ Analysis of CaCo 2 cell RNA using solution hybridization / RNase protection assays yielded two protected fragments , approximately 379 bases in length , with a 394 base IGF 1 receptor riboprobe and a 250 base protected fragment with a 260 base IGF II / M6P receptor riboprobe . ^^^ In conclusion , ( 1 ) CaCo 2 cells express both IGF 1 receptor mRNA and IGF II / M6P receptor mRNA and contain functional IGF 1 receptor and IGF II / M6P receptor protein . ( 2 ) CaCo 2 cells express IGF 2 mRNA and secrete IGF 2 immunoreactivity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA was detected in extrahepatic tissues only , and was not affected by either GH or IGF 1 treatment . ^^^
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In order to understand the basis for the selective action of IGF 1 , the levels of mRNAs encoding IGF 1 , IGF binding proteins ( IGFBPs ) , IGF 1 receptor , and GH receptor / binding protein ( GHR / GHBP ) were determined in rats given TPN and treated with GH , IGF 1 , or GH + IGF 1 . ^^^ The levels of IGF 1 receptor and IGFBP 1 , 2 , 4 , and 6 mRNAs were extremely low and / or were not altered by any of the treatments . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Human neuroblastoma cells use either insulin like growth factor 1 or insulin like growth factor 2 in an autocrine pathway via the IGF 1 receptor : variability of IGF , IGF binding protein ( IGFBP ) and IGF receptor gene expression and IGF and IGFBP secretion in human neuroblastoma cells in relation to cellular proliferation . ^^^ A 520 bases human IGF 1 , a 556 bases human IGF 2 , a 480 bases human IGF 1 receptor and a 250 human IGF II / mannose 6 phosphate ( M6P ) receptor probe were radiolabelled as were human IGFBP 1 , 2 , 3 , 4 , 5 and 6 probes . ^^^ In addition , a 400 bases protected band was seen with the IGF 1 receptor probe and a 260 bases protected band with the IGF IIM6P receptor probe in either cell line . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to fully understand the role of IGF 1 in the skin and its appendages , however , a comprehensive study that details the expression of IGF 1 and the IGF 1 receptor in sections of human skin is needed . ^^^ We have observed that ( 1 ) dermal fibroblasts produce IGF 1 , ( 2 ) the epidermal basal keratinocytes are IGF 1 negative but IGF 1 receptor positive , and ( 3 ) the keratinocytes of the stratum granulosum produce IGF 1 . ^^^ The distribution of IGF 1 and its receptor in the hair follicle indicates that IGF 1 may be a morphogen , not a mitogen , at those sites , because their proliferating cells , but not their differentiating cells , are IGF 1 receptor negative . ^^^ Further , IGF 1 receptor expression by the dermal papilla appears to be switched off during the transition from anagen to catagen , which implies a regulatory role for IGF 1 during the hair growth cycle . . ^^^
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In normal appearing white matter , we found that IGF 1 receptor densities and binding characteristics were not different between MS patients and controls . ^^^
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CONCLUSION : Differences in the proliferative rate of normal and psoriatic keratinocytes may be in part due to differences in signal transduction distal from the IGF 1 receptor or in the cooperation of the EGF and the IGF 1 receptor . . ^^^
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Moreover , the addition of CF CM to PTC increased cell associated IGFBP 3 on PTC surfaces , without changes in IGF 1 receptor numbers or affinity and without changes in PTC mRNA for IGFBP 3 . ^^^ Des ( 1 3 ) IGF 1 , an analog that binds to the IGF 1 receptor but not to IGFBPs , provided a less potent stimulus for PTC growth compared with IGF 1 , indicating that cell associated IGFBP 3 facilitates the action of IGF 1 on PTC . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recent studies strongly suggest that insulin is acting through its own receptor ( rather than the IGF 1 receptor ) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release . ^^^
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Interaction between p55PIK and IGF IR was seen not only in the yeast two hybrid system , but also using in vitro binding and coimmunoprecipitation of lysates from IGF 1 stimulated 293 cells overexpressing p55PIK . ^^^
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The fragment was recognized by two anti IGF 1R monoclonal antibodies , 24 31 and 24 60 , but showed no detectable binding of IGF 1 or IGF 2 . ^^^
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Because the insulin like growth factor ( IGF ) autocrine paracrine system may provide an important signaling mechanism between TM cells and the outflow pathway , the expression of IGFBP 5 and IGF 1 receptor in the TM was characterized . ^^^ Western immunoblots and confocal immunohistochemistry were used to evaluate the protein expression patterns of IGFBP 5 and the IGF 1 receptor . ^^^ In addition , the IGF 1 receptor was expressed by the TM and showed cell surface staining by immunohistochemistry . ^^^ CONCLUSIONS : IGFBP 5 and IGF 1 receptor were expressed at significant levels by TM cells and may serve an important role in trabecular function . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It further possibly allowed to relate the GCY gene ( s ) to the control of GH or IGF 1 receptor or post receptor pathway , being the alteration of this gene ( s ) consistent with the hormonal pattern of the patient . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin , which does not bind to IGFBPs , was a potent mitogenic factor in these cells at a high concentration ( 10 nmol / L ) , suggesting a cross reaction to IGF 1 receptor . ^^^ This regulation on IGFBPs was IGF 1 receptor independent . ^^^ In fact , ( 1 ) IGFBP mRNA levels were not modified after stimulation with 100 nmol / L IGF 1 , ( 2 ) 100 nmol / L IGF plus an equimolar concentration of alpha IR 3 did not affect IGFBP production , ( 3 ) Des ( 1 3 ) IGF 1 had no effect on IGFBP modulation , whereas at 10 nmol / L it enhanced BREC thymidine cell incorporation , and ( 4 ) 100 nmol / L insulin , which at this concentration can cross react with the IGF 1 receptor , did not modify the IGFBP pattern . ^^^ IGF actions are modulated by locally produced endothelial IGFBPs , and in turn , these endothelial IGFBPs are regulated , via in IGF 1 receptor independent mechanism , by the presence of IGFs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reduction of ventral prostate weight by finasteride is associated with suppression of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor genes and with an increase in IGF binding protein 3 . ^^^ Finasteride also inhibited the expression of insulin like growth factor ( IGF ) 1 and IGF 1 receptor genes in the ventral prostate . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor protein was also measured by Western immunoblot . ^^^ In the distal colon , IGF 1 receptor gene expression and protein increased significantly as the percentage of CO increased . ^^^ Thus IGF 1 and IGF 2 receptor mRNA and IGF 1 receptor protein level in colon mucosa were significantly altered by dietary fat source and quantity , thereby suggesting a potential influence of dietary fat on the endocrine regulation of colon cell mitogenesis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Elucidation of novel pathways downstream of p 53 have established a link between this important tumor suppressor gene and the insulin like growth factor 1 receptor ( IGF 1r ) , either via direct regulation of IGF 1 receptor levels , or modulation of IGFs via transactivation of the insulin like growth factor binding protein 3 ( IGF BP 3 ) gene . ^^^ The p53 / IGF 1 receptor axis in the regulation of programmed cell death . ^^^
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Affinity labelling experiments demonstrated that IGF 1 receptor levels increased initially after castration with peak binding at 24 hours , then declined to levels lower than control . ^^^
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Taken together , our results indicate not only the presence of both IGF 1 and IGF II / Man6P receptors on BAM , but also provide evidence of the linkage of the IGF 1 receptor to the inositol phosphate system . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptor ( IR ) and the related insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) mediate a variety of metabolic and mitogenic cellular responses , some of which may involve unidentified receptor targets . ^^^ A role of mSH 2 B in IGF 1 and insulin action was suggested by the interaction of the SH 2 domain with activated IGF IR and IR catalytic fragments but not with an inactive IR catalytic fragment in the yeast two hybrid system in vivo and by the hormone dependent association of a glutathione S transferase ( GST ) SH 2 domain fusion protein of mSH 2 B with both receptors in cell extracts . ^^^ IR and IGF IR Tyr phosphorylation motifs were not identified in the complete SH 2 B primary structure , suggesting that it may participate as an adapter rather than a substrate in the IGF 1 and insulin signaling pathways . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin / IGF 1 hybrid receptors composed of an insulin receptor ( IR ) alphabeta hemireceptor and a type 1 IGF receptor ( IGF IR ) alphabeta hemireceptor are formed in tissues expressing both molecules . ^^^
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The receptor for the type 1 insulin like growth factor ( IGF 1R ) and its ligands IGF 1 and IGF 2 play important roles in the maintenance of the malignant phenotype . ^^^
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This insulin induced desensitization to IGF 1 is mediated by specific insulin receptors on bovine fibroblasts and occurs distally to IGF 1 receptor engagement and activation . ^^^ In the present study , we use this model system to determine insulin and IGF 1 receptor interplay in the regulation of proto oncogenes involved in mitogenesis . ^^^ These data indicate significant insulin / IGF 1 receptor interplay in normal bovine fibroblasts and suggest that insulin receptor initiated signaling can profoundly alter proto oncogene expression induced by growth factors sharing components of a common intracellular signaling network . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The patient ' s fibroblasts showed normal binding of IGF 1 , normal phosphorylation of the beta subunit of the IGF 1 receptor , and normal [ 3H ] thymidine incorporation in response to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study investigates the relationship between IGF 1 receptor internalization and signaling via IRS 1 and Shc . ^^^ A mutation in the C terminus of the IGF 1 receptor decreased both the rate of receptor internalization and IGF 1 stimulated Shc phosphorylation by more than 50 % , but did not affect IRS 1 phosphorylation . ^^^ Low temperature ( 15 degrees C ) decreased IGF 1 receptor internalization and completely inhibited Shc phosphorylation . ^^^ These data support the concept that Shc / mitogen activated protein kinase pathway activation requires IGF 1 receptor internalization , whereas the IRS 1 pathway is activated by both cell surface and endosomal receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The removal of 108 aa from the C terminus of the IGF 1 receptor abolishes the transforming ability of the receptor without affecting its ability to induce cell growth . ^^^ Using differential display , we have examined differences in gene expression between cells expressing a wild type , transforming IGF 1 receptor and cells expressing a C terminally truncated , nontransforming IGF 1 receptor . ^^^ We have cloned a novel 6 . 3 kb cDNA transcript ( DBI 1 ) which is expressed at much lower levels in cells containing the wild type IGF 1 receptor . ^^^ Overexpression of DBI 1 in cells which contain the wild type IGF 1 receptor diminishes the mitogenic response to IGF 1 . . ^^^
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Finally , the AA address briefly a third group of ( prognostic ) factors that reflect the interaction between the neoplastic cells and their microenvironment : extracellular matrix and proteolytic enzymes ( laminin , collagen 4 , fibronectin , collagenases , alpha 1 anti trypsin ) and lymphocytic infiltration ( S 100 positive cells , IGF 1 and IGF 1 receptor ) . . ^^^
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The central importance of IGF for normal development and growth has been illustrated by the severe growth retarded phenotype exhibited by IGF 1 , IGF 2 or IGF 1 receptor `` knockout ' ' mice . ^^^
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IGF 1 actions could be mimicked by insulin and IGF 2 at concentrations that correspond to the pharmacology of the IGF 1 receptor , the latter for which the mRNA was detected in undifferentiated stem cell progeny . ^^^
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Furthermore , normal betaTCs can be sensitized to chemotherapy when transfected with a dominant negative mutant of the IGF 1 receptor . ^^^
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Genistein , whether added during preincubation or with IGF 1 at the start of incubation , significantly inhibited the IGF 1 induced stimulation of protein synthesis , autophosphorylation of the beta subunit of IGF 1 receptor and inhibition of ERK . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It was found that the expression of insulin like growth factor 1 ( IGF 1 ) , insulin like growth factor 2 ( IGF 2 ) , and the insulin , IGF 1 and IGF 2 receptor transcripts ( IGF1R and IGF2R , respectively ) was present in all term placentas examined . ^^^
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Insulin and insulin like growth factor 1 ( IGF 1 ) treatment of cells overexpressing the insulin receptor or the IGF 1 receptor promotes phosphorylation and activation of Janus kinases JAK 1 and JAK 2 but not of TYK 2 . ^^^
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When expressed in Saos 2 , osteosarcoma cells that lack p 53 , wild type p 53 decreased , whereas mutated p 53 increased IGF IR expression , and IGF 1 induced tyrosine phosphorylation of the IGF IR . ^^^ In conclusion , p 53 regulates IGF IR expression , as reflected by a reduction in IGF IR protein and a parallel reduction in IGF 1 induced tyrosine phosphorylation of the IGF IR and IRS 1 in an osteosarcoma cell line . ^^^ These data indicate that the IGF 1 receptor is a physiological target for p 53 in osteosarcoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( 9 . 4+ / 96 vs . 10 . 5+ / 57 per microg protein ) and estrogen receptor ( 18 . 4+ / 1 . 14 vs . 19 . 6 + 1 . 6 per microg protein ) levels were not significantly different in tumors from exercised animals compared to those from sedentary animals . ^^^ For both sets of tumors , correlation between estrogen receptor content and growth rate is positive , while the correlation between IGF 1 receptor content and growth rate is negative . ^^^ The results of this study suggest that exercise prior to NMU administration does not affect tumor burden but does alter tumor growth rate , which is not due to differences in estrogen receptor or IGF 1 receptor content . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Indirect three step immunohistochemistry was performed using anti IGF 1 , IGF 1 receptor alpha ( IGF IR alpha ) , IGF IR beta , PDGF BB and PDGF receptor ( PDGF R ) antibodies and visualized by peroxidase staining . ^^^ RESULTS : The most striking difference between tissues from IHPS patients and controls was the marked increase in IGF 1 , IGF IR alpha , IGF IR beta and PDGF R in the hypertrophic circular muscle layer , and , to a lesser degree , in the longitudinal muscle in pyloric stenosis . ^^^
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Genetic crosses of insulin receptor and insulin like growth factor 1 ( IGF 1 ) receptor deficient mice indicate , however , that insulin receptors play an important role in late gestational growth , and that absence of growth retardation in insulin receptor deficient ( IR / ) mice may be due to a compensatory increase in IGF 1 receptor levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since insulin like growth factor 1 ( IGF 1 ) is an important hormone regulator of intestinal proliferation , this study examined the effects of dietary protein content and tumor necrosis factor ( TNF ) on mRNA levels of IGF 1 , IGF 1 receptor , IGF binding protein 3 ( IGFBP 3 ) , and IGFBP 4 and on the histology of the colon , jejunum , and ileum in protein malnourished rats . ^^^
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Using a kinase deficient p 125 ( Fak ) mutant , we found that this protein is a direct substrate of the insulin and IGF 1 receptor tyrosine kinases . ^^^
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Peri implantation mouse embryos synthesize insulinlike growth factor ( IGF ) 2 ligand , insulin receptor , IGF 1 receptor , and IGF 2 receptor and respond to IGF 2 , IGF 1 , and insulin metabolically and mitogenically . ^^^
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Analysis of the IGF 1 receptor was done by staining the sample with a monoclonal anti IGF 1 receptor antibody ( alphaIR 3 clone ) and goat anti mouse phycoerythrin labelled antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here we will discuss signaling by the IGFs , focusing specifically on the structure and function of the IGF 1 receptor and the domains of this receptor responsible for distinct IGF functions : mitogenesis , transformation , and protection from apoptosis . ^^^
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The biological actions of the insulin like growth factors IGF 1 and IGF 2 are mediated by their activation of the IGF IR , a transmembrane tyrosine kinase linked to the ras raf MAPK cascade . ^^^
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Twenty four hours after the insult , tissue mRNAs for IGF 1 , the IGF 1 receptor , and IGF binding proteins ( IGFBP ) 1 and 3 were assayed in cortex , medulla , and liver by solution hybridization RNase protection assay , and IGFBPs were measured in serum and tissue by Western ligand blotting . ^^^
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Additionally , the attenuation in the ability of IGF 1 to elevate nociceptive threshold may be a consequence of reduced gene expression of IGF 1 receptor within the spinal cord . . ^^^
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Effects of norepinephrine on expression of IGF 1 / IGF 1R and SERCA 2 in rat heart . ^^^ Tissue insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF 1R ) play an important role in the regulation of the hyperplastic capacity of cardiac myocytes . ^^^ The present study examined the effects of elevated levels of NE on expression of IGF 1 / IGF 1R and SERCA 2 mRNAs . ^^^ Levels of expression of IGF 1 / IGF 1R and SERCA 2 mRNAs were determined by ribonuclease protection assay and by Northern blotting , respectively . ^^^ RESULTS : NE treatment significantly increased IGF 1 mRNA levels in both left and right ventricle ; however , levels of IGF 1R increased in the left but not the right ventricle . ^^^
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Moreover , IGF 1 carriers ( IGFBPs ) and IGF 1 receptor are altered in ARF and modify the growth factor bioactivity . ^^^
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In acutely injured proximal tubular cells , IGF 1 receptor mRNA levels decrease , but the remaining receptors are functional as indicated by ligand induced phosphorylation of the IGF 1 receptor beta subunit . ^^^
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Before and after induction , c myc , IGF 2 , IGF 1 receptor , and IGF 2 receptor were constitutively expressed by all four cell lines . ^^^
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Since IRS 2 was present in IGF 1R precipitates and a recombinant form of IGF 1 ( long R 3 IGF 1 ) stimulated formation of Tyr ( P ) IRS 2 , hormonal activation of this docking protein probably occurs through the IGF 1R . ^^^
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The studies were undertaken to investigate interaction between these two hormone systems , that is , ( 1 ) to study effects of 1 alpha , 25 ( OH ) 2D3 on IGF type 1 receptors ( IGFIR ) , on IGF 1 stimulated cell replication , colony formation , and on alkaline phosphatase activity ( AP ) , and conversely , ( 2 ) to study the effect of IGF 1 on vitamin D receptor ( VDR ) expression on 1 alpha , 25 ( OH ) 2D3 stimulated growth parameters and on AP activity . ^^^
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Interestingly , IGF 1 receptor mRNA levels were unchanged while plasma membrane IGF 1 receptor number increased two fold . ^^^ IGF 1 receptor autophosphorylation and tyrosine kinase activity were intact despite severe uremia for up to 6 days . ^^^
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METHODS : Human glioblastoma cells were treated with or without TAM and / or IGF 1 in vitro and evaluated for : viability by the 3 ( 4 , 5 dimethylthiazol 2 yl ) 2 , 5 diphenol tetrazolium bromide cleavage assay ; apoptosis by histochemical analysis of nuclear morphology and 3 ' OH DNA fragments ; and expression of the IGF 1 receptor , and the bcl 2 , bcl xL , and bax proteins by immunoblot analysis . ^^^ The WITG 3 cells expressed IGF 1 receptor proteins and demonstrated IGF 1 binding . ^^^
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Because of their known roles in retinal neurogenesis , we have chosen to focus future studies on insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor . ^^^
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The IGF 1 receptor ( IGF 1 R ) mRNA expression was three fold higher in early cultured HSCs than in culture activated HSCs . ^^^
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Our data suggest that IGF 1 , produced by stromal cells in hyperplasia , exerted its effects , through a paracrine mode , on epithelial cells which were IGF 1 receptor ( IGF 1R ) positive . ^^^ The production of IGF 1 appeared to switch to epithelial cells in adenocarcinoma , through which it regulated tumor cell growth via autocrine mode by binding to IGF 1R of carcinoma cells . ^^^
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However , replacement of the C terminal domain of the IGF 1 receptor beta subunit with the corresponding segment of the insulin receptor restored pp 120 phosphorylation by the chimeric receptor . ^^^ Since pp 120 stimulates receptor mediated insulin endocytosis when it is phosphorylated , we examined whether pp 120 regulates IGF 1 receptor endocytosis in transfected NIH 3T3 cells . pp 120 failed to alter IGF 1 receptor endocytosis via either wild type or chimeric IGF 1 receptors . ^^^
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IGF 1 binding to cell surface receptors stimulated phosphorylation of 97 kDa and 93 kDa subunits of the IGF 1 receptor and incorporation of [ 3H ] thymidine into RINm5F cells . ^^^
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The allografts were harvested 14 days later and processed for immunohistochemical staining for alpha actin , growth factors ( IGF 1 , IGF 1 receptor , platelet derived growth factor BB , and basic fibroblast growth factor ) , and immunological markers ( major histocompatibility complex class 2 antigen , macrophage , and CD 4 and CD 8 positive T cells ) . ^^^ RESULTS : By 14 days , the ex vivo IGF 1 donor aorta treatment with IGF 1 increased in a concentration dependent manner the expression of IGF 1 and IGF 1 receptor in both the intima and the adventitia . ^^^
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In addition , to analyze further the mechanism of hCG signaling involved in apoptosis inhibition , we examined the expression of LH / hCG receptors and the regulation by hCG for apoptosis inhibitory pathways , such as the bcl 2 / bax system and the insulin like growth factor 1 ( IGF 1 ) / IGF 1 receptor ( IGFR ) system . hCG did not increase cell proliferation in either cell line . ^^^
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However , c Ets 1 and GHF 1 act synergistically in HeLa cells with the IGF 1 receptor , reconstituting pituitary IGF 1 responsiveness . ^^^
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Cell systems derived from knockout mice for the insulin receptor ( IR ) or the IGF 1 receptor ( IGF 1R ) represent unique tools for dissecting complex interplay in the actions of insulin and insulin like growth factors through their cognate versus non cognate receptor . ^^^
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We have previously shown that insulin like growth factor 1 ( IGF 1 ) activation of the IGF 1 receptor rescues SH SY5Y human neuroblastoma cells from high glucose mediated programmed cell death ( PCD ) . ^^^ In the current study , we further explored the potential points in the cell death cascade where IGF 1 receptor activation may afford neuroprotection . ^^^
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Renal IGF 1 mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes , while renal IGF 1 receptor ( IGF IR ) mRNA was unchanged in rats from either group . ^^^
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In mammalian cells , the insulin receptor substrate 1 protein ( IRS 1 ) is a specific substrate for insulin and IGF 1 receptor tyrosine kinases which is involved in mediating metabolic and mitogenic actions of insulin and IGFs . ^^^
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Consequently the regulation of IGF 1R expression by IGF 1 and the activation events in human blood T lymphocytes and the Jurkat T cell line were now investigated . ^^^ IGF 1R expression in nonstimulated Jurkat cells was confirmed and downregulation by IGF 1 was demonstrated . ^^^ In addition , both cell types showed a time dependent reduction in the number of IGF 1R positive cells following activation , which was increased by IGF 1 . ^^^
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While both proteins are substrates involved in IGF 1 receptor signaling , they apparently demonstrate important different properties and different biological responses . ^^^
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IGF 1 receptor mRNA was detected in the cultured pituitary cells using reverse transcription ( RT ) PCR , indicating that mouse pituitary cells expressed IGF 1 receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The degradation of IGFBP 4 was not stimulated when cells were incubated with the IGF 1 analogue , LR 3 IGF 1 , and insulin which binds to IGF 1 receptor but has little or no affinity for IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In situ hybridyzation was used to detect the expression of IGF 1 and IGF 1 receptor ( IGF 1R ) in the granulosa cell obtained from follicular aspiration in women undergoing IVF egg retrieval procedures . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHOD : The expression of IGF 1 receptor gene in the ovarian stroma from 35 cases of PCOS ( obese : 15 cases ; nonobese : 20 cases ) and 20 cases of control were quantitatively determined by reverse transcript polymerase chain reaction ( RT PCR ) combined with beta ( 2 ) micro globlin ( beta ( 2 ) MG ) gene as inner control to amplificate sychronously . ^^^ RESULTS : The expression of IGF 1 receptor in PCOS ovary stroma was significantly greater than in the control group ( P < 0 . 001 ) . ^^^ The nonobese group presents more enhancement than obese group in IGF 1 receptor gene expression . ^^^ CONCLUSIONS : The expression of IGF 1 receptor in PCOS ovarian stroma is abnormally excessive and the nonobese PCOS have more potential action of IGF 1 system in ovary stroma . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dexamethasone impairs growth hormone ( GH ) stimulated growth by suppression of local insulin like growth factor ( IGF ) 1 production and expression of GH and IGF 1 receptor in cultured rat chondrocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ethanol inhibited IGF 1 mediated neuronal survival but did not inhibit IGF 1 receptor binding or the neurotrophic action of elevated K+ , and failed to potentiate cell death in the presence of 5 mM K+ . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Leu IGF 1 , which has reduced affinity for the IGF 1 receptor but normal affinity for IGFBPs , failed to increase IGFBP 3 protein and mRNA levels , whereas B chain IGF 1 ( normal affinity for the receptor but reduced affinity for IGFBPs ) elicited the response , thus implying an IGF 1 receptor mediated event . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) 1 signaling through the IGF 1 receptor modulates cellular adhesion and proliferation and the transforming ability of cells overexpressing the IGF 1 receptor . ^^^ The determination of the exact pathways emanating from the IGF 1 receptor that are involved in mediating these signals will contribute greatly to the understanding of IGF 1 action . ^^^ We have previously shown that replacement of tyrosine residues 1250 and 1251 in the carboxyl terminus of the IGF 1 receptor abrogates IGF 1 induced cellular proliferation and tumor formation in nude mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Significantly , decreased levels of IGF 1 receptor and its mRNA was noted in the dentate and CA 1 CA4 regions of the hippocampus of the ADX animals , suggesting that the level and expression of IGF 1 receptors in the hippocampus is influenced by adrenal hormones . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expression of the IGF 1 receptor has been demonstrated in a variety of human tumor cell lines including ovarian cancer cells . ^^^ Phosphorothioate antisense oligodeoxynucleotides ( S ODNs ) were analyzed for their potential to suppress the IGF 1 receptor in the NIH : OVCAR 3 ovarian cancer cell line . ^^^ Our data demonstrate the potency of antisense S ODNs to target the IGF 1 receptor message and show that antisense strategies against the IGF 1 receptor may provide new strategies for the therapy of ovarian cancer . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Stimulation of tumor growth by recombinant human insulin like growth factor 1 ( IGF 1 ) is dependent on the dose and the level of IGF 1 receptor expression . ^^^ The therapeutic uses of IGF 1 have been discussed extensively ; however , excessive activity of the IGF ligands and IGF 1 receptor has been suggested as a factor in tumorigenesis . ^^^ This study examined whether systemic recombinant human IGF 1 ( rhIGF 1 ) therapy affects the growth of fibrosarcomas derived from fibroblasts expressing the IGF 1 receptor at high or naturally occurring densities ( 1 . 9 10 10 ( 5 ) compared with 1 . 6 10 10 ( 4 ) IGF 1 receptors / cell ) in athymic nude mice . ^^^ Treatment with 4 or 10 mg / kg rhIGF 1 resulted in a marked reduction in the tumor latency and stimulated the growth of fibrosarcomas that overexpressed the IGF 1 receptor . ^^^ The latency and growth of fibrosarcomas expressing parental levels of the IGF 1 receptor were not affected by rhIGF 1 therapy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both TCDD and BaP appeared to mimic signaling through the IGF 1 receptor ( IGF IR ) , as evidenced by increased tyrosine phosphophorylation of IGF IRbeta , IRS 1 and Shc . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This is the first study to give a complete overview of the mRNA expression patterns of Igf 1 , Igf 2 , type 1 Igf receptor ( Igf1r ) and six Igf binding proteins ( IGFBP 1 6 ) in embryonic mouse limbs , at various stages of development , by whole mount in situ hybridization ( ISH ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study was conducted to determine whether IGF 1 is present in bovine seminal plasma , whether sperm cells express the IGF 1 receptor ( IGF IR ) , and whether IGF 1 affects sperm motility . ^^^ The presence of IGF IR on sperm , the presence of IGF 1 in semen , and the ability of IGF 1 to stimulate sperm motility provide evidence that the IGF system may be involved in the fertilization process in the bovine species . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tumor cells from patient 1 exhibited insulin growth factor 1 ( IGF 1 ) and insulin like growth factor 1 receptor ( IGF IR ) mRNA transcripts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Highly invasive murine Lewis lung carcinoma subline H 59 cells , in which expression of the IGF 1 receptor ( IGF IR ) was blocked by antisense mRNA , had a significantly reduced invasion in reconstituted basement membrane ( Matrigel ) as compared with that of controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , agonists that bind to G protein coupled receptors , such as angiotensin 2 and thrombin , interact with the IGF 1 receptor signalling pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients , we determined the concentrations of insulin and c peptide as well as insulin receptor binding and IGF 1 receptor binding in several regions of postmortem brain cortex during aging and Alzheimer ' s disease . ^^^ IGF 1 receptor densities were unchanged in aging and in SDAT . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Src stimulates insulin like growth factor 1 ( IGF 1 ) dependent cell proliferation by increasing IGF 1 receptor number in human pancreatic carcinoma cells . ^^^ Western blotting and competition binding studies demonstrated 2 . 3 + / 0 . 2 fold increase in IGF 1 receptor expression and 2 . 8 + / 0 . 4 fold increase in IGF 1 specific binding sites / cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The action of IGF 1 appears to involve binding proteins , transport to the site of injury and the IGF 1 receptor and inhibition of apoptosis , but might also involve generation of GPE which itself appears to be neuroprotective . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To provide evidence for this idea , we showed that mild trypsin treatment of living LoVo C 5 cells partially restored alpha / beta cleavage of IGF IR , and greatly enhanced ( 6 fold ) the IGF 1 binding capacity of LoVo C 5 cells , but did not restore IGF IR signaling activity . ^^^ Moreover , LoVo C 5 cells were totally unresponsive to IGF 1 in terms of cell migration , in contrast to fully processed IGF IR HT 29 D4 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA was increased 46 % , IGF 1 receptor protein was increased 65 % , and the binding capacity of the IGF 1 high affinity site was increased sixfold ( P < 0 . 05 ) with chronic wheel exercise . ^^^ This study demonstrates that old animals retain a plasticity for IGF 1 receptor and glucose transporter expression that may have valuable physiological consequences . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
After IGF 1 stimulation , activated IGF IR was found in anti FLAG immunoprecipitates and , conversely , FLAG hSOCS 2 was found in anti IGF IR immunoprecipitates . ^^^ These results raise the possibility that SOCS proteins may also play a regulatory role in IGF 1 receptor signaling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The recent report of partial insulin resistance in IUGR subjects raises the possibility of an IGF 1 receptor or post receptor mediated defect . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Biosensor interaction analysis binding studies demonstrate the involvement of Arg 36 Arg37 and Arg 50 in IGFBP 1 binding , while experiments with the IGF 1 receptor implicate Arg 21 , Arg 36 Arg37 , and Arg 56 as part of the receptor binding epitope . ^^^ These overlapping binding surfaces explain why IGF 1 receptor and IGFBP 1 binding to IGF 1 is competitive . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : A crucial step in cell cycle progression is the activation of the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) by its ligand . ^^^ RESULTS : Estradiol 17 beta treatment of rabbits significantly inhibited IGF IR expression in the allograft coronary arteries and abrogated cell proliferation induced by IGF 1 in the allograft aorta compared with placebo treated recipients ( 65 . 4+ / 5 % vs . 500+ / 139 % , P < 0 . 002 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine whether blocking alphaVbeta 3 occupancy could alter IGF 1 receptor mediated signal transduction , the ability of IGF 1 to stimulate phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was analyzed . ^^^ To determine whether these effects were caused by alterations in receptor kinase activity , the IGF 1 receptor was immunoprecipitated and then analyzed for phosphotyrosine . ^^^ Echistatin ( 10 ( 7 ) M ) significantly reduced IGF 1 stimulated tyrosine phosphorylation of the IGF 1 receptor beta subunit . ^^^ We conclude that occupancy of the alphaVbeta 3 integrin is necessary for IGF 1 to fully activate the kinase activity of the IGF 1 receptor and phosphorylate IRS 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that this deletion increases the basal activity of the IGF 1 receptor tyrosine kinase and activates PI 3 kinase , but is unable to stimulate MAP kinase in the absence of ligand . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Following activation of the IGF 1 receptor , the mitogen activated protein kinase and phosphatidylinositide 3 ' kinase ( PI3 ' K ) pathways are activated and result in cellular proliferation and inhibition of apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined the effects of zinc depletion from the culture media of Swiss 3T3 cells on the cell cycle and IGF 1 receptor expression . ^^^ Fetal bovine serum deprivation reduced IGF 1 receptor expression whereas the absence of zinc had little effect on receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study was undertaken to biochemically and immunohistochemically clarify the expression of basic fibroblast growth factor ( bFGF ) , insulin like growth factor 1 ( IGF 1 ) , fibroblast growth factor receptor ( bFGFR ) , insulin like growth factor 1 receptor ( IGF IR ) and vascular smooth muscle cell ( VSMC ) growth by using Streptozotocin ( STZ ) treated rat serum . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Genes encoding insulin like growth factors ( IGF 1 and IGF 2 ) and their type 1 receptor ( IGF IR ) have also been disrupted . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Affinity cross linking with [ 125I ] IGF 1 using disuccinimidyl suberate and SDS PAGE under reducing conditions yielded a polypeptide band with apparent Mr 130 , 000 , consistent with the alpha subunit of the IGF 1 receptor . ^^^ These results demonstrate IGF 1 receptor expression by the enteroendocrine cell line STC 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Chemical crosslinking detected a protein with an apparent mass of 175 kDa and its identity as the IGF 1 receptor alpha subunit was confirmed by Western blotting . ^^^ Immunofluorescence microscopy verified that both insulin and IGF 1 receptors were present , although measurement of IGF 1 receptor quantity revealed they were less abundant than insulin receptors . ^^^ Interestingly , addition of insulin to quiescent H4IIE cells , which stimulates cell proliferation , further increased IGF 1 receptor protein levels with a peak at 12 24 h . ^^^ Distinct modes of regulating IGF 1 receptor expression are indicated . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 acts through the IGF 1 receptor ( IGF IR ) and its actions may be modified by IGF 1 binding proteins ( IGFBPs ) . ^^^ IGF 1 binding proteins , IGF 1 binding protein mRNA and IGF 1 receptor mRNA in rats with acute renal failure given IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We and others have described a linear survival signaling cascade used by insulinlike growth factor 1 ( IGF 1 ) that consists of the IGF 1 receptor , phosphoinositide 3 kinase ( PI 3 kinase ) , Akt , and Bad . ^^^ These findings demonstrate the existence of a new survival signaling pathway independent of PI 3 kinase , Akt , and new transcription and which is evident in fibroblasts overexpressing the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of an antisense expression plasmid to the IGF 1 receptor on hamster mesothelioma proliferation . ^^^ Expression of IGF 1 and IGF 1 receptor ( IGF 1 R ) genes was identified from H9A RNA using RT PCR and Northern blot analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Growth hormone ( GH ) receptor and IGF 1 receptor messenger RNA expression in peripheral lymphocytes from patients with GH deficiency and acromegaly . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Gene expression of IGF 1 , IGF 1 receptor ( IGF 1 R ) and IGF binding protein 1 ( IGFBP 1 ) was examined in renal tissue from normal DM animals and DM animals treated with Oc 10 , 20 and 100 microg / day . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin receptor related receptor ( IRR ) , a member of the insulin receptor tyrosine kinase family , has structural homology to the insulin receptor ( IR ) and the IGF 1 receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and insulin like growth factor 1 ( IGF 1 ) both stimulated AIB uptake , but the higher concentrations of insulin necessary to increase uptake to a level comparable to that of IGF 1 stimulation suggested that insulin could be acting through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the other hand , the sustained activation of the IGF 1 receptor ( IGF IR ) by the overexpression of IGF 2 has been found to contribute to the development of the estrogen independent phenotype in breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We demonstrate here that the antiestrogen ICI 182780 ( ICI ) at 10 ( 8 ) m decreases IGF 1 receptor ( IGF IR ) mRNA levels by 70 % after treatment for 48 h . ^^^ Our data suggest that attenuation of IGF 1 responsivity by ICI may be due in part to reducing the IGF IR expression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , the effect of 9 nmol / l GH on 1 . 25 ( OH ) 2D3 and 24 , 25 ( OH ) 2D3 production was blocked in the presence of IGF 1 receptor monoclonal antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Structure of the IGF binding domain of the insulin like growth factor binding protein 5 ( IGFBP 5 ) : implications for IGF and IGF 1 receptor interactions . ^^^ Remarkably , the IGF 1 receptor binding assays of IGFBP 5 showed that IGFBP 5 inhibits the binding of IGFs to the IGF 1 receptor , resulting in reduction of receptor stimulation and autophosphorylation . ^^^ Compared with the full length IGFBP 5 , the smaller N terminal fragments were less efficient inhibitors of the IGF 1 receptor binding of IGFs . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We studied the influence of 24 hour hypoxia ( 10 % oxygen ) , 48 hour hyperoxia ( 75 % oxygen ) , and relative hypoxia ( shifting from 48 hours in 75 % oxygen to 24 hours in room air ) on the gene expression of IGF 1 , IGF 1 receptor ( IGF IR ) , and IGF binding protein 1 ( IGFBP 1 ) , IGFBP 2 , and IGFBP 3 in retina using a solution hybridization RNase protection assay . ^^^ Hypoxia induced a significant increase in retinal IGF IR ( 178 % ) , IGFBP 2 ( 227 % ) , and IGFBP 3 ( 317 % ) mRNA ; however , retinal IGF 1 mRNA was reduced , as well as serum growth hormone ( GH ) . ^^^ Relative hypoxia caused a similar but less pronounced trend in the gene expression of IGF IR and the binding proteins , whereas retinal IGF 1 mRNA was unchanged and serum GH was elevated . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
As the IGF 1 receptor is expressed from the morula stage onwards , the embryos are capable of responding to insulin and IGF 1 , which is present in the oviductal and uterine secretions that surround them . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report here that IGF 1 stimulated the tyrosine phosphorylation of the type 1 IGF receptor ( IGF IR ) and insulin receptor substrate 2 ( IRS 2 ) in a time and concentration dependent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin treatment yielded similar results at 10 fold higher doses , indicating that this response is IGF 1 receptor dependent . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Regulation of steroidogenesis by insulin like growth factors ( IGFs ) in adult human adrenocortical cells : IGF 1 and , more potently , IGF 2 preferentially enhance androgen biosynthesis through interaction with the IGF 1 receptor and IGF binding proteins . ^^^ Although both IGF receptors are present in adult human adrenocortical cells , the steroidogenic effect of IGF 2 is mediated through the IGF 1 receptor , since [ Arg 54 , 55 ] IGF 2 , which only binds to the IGF 1 receptor , was equipotent with native IGF 2 , whereas [ Leu 27 ] IGF 2 , which preferentially binds to the type 2 IGF receptor , did not show any effect . ^^^ In conclusion , these results demonstrate that : ( 1 ) IGF 2 stimulates basal as well as ACTH induced DHEA S and cortisol secretion from adult human adrenocortical cells more potently than IGF 1 ; ( 2 ) both IGFs predominantly stimulate androgen biosynthesis ; ( 3 ) the steroidogenic effect of IGF 1 and IGF 2 is mediated through interaction with the IGF 1 receptor ; ( 4 ) the different steroidogenic potency of IGF 1 and IGF 2 might be explained by interaction of these ligands with locally produced IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Maximal and high affinity binding sites for IGF 1 receptor in the HOCM were greater ( P < 0 . 01 and P < 0 . 05 ) than the levels in AS , SA , and TM . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Human preimplantation embryos express mRNA for insulin like growth factor 1 receptor ( IGF IR ) but the ligand , insulin like growth factor 1 ( IGF 1 ) , is not expressed by the embryo until after implantation . ^^^ The effect of IGF 1 was mediated through the IGF 1 receptor . ^^^ Immunocytochemistry using an alphaIR 3 antibody confirmed the presence of IGF 1 receptor in human blastocysts and the same antibody completely inhibited the stimulation of blastocyst formation by IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , in vitro analysis demonstrated that transmigrated 5T2 MM cells have a higher expression of IGF 1 receptor , both in bone marrow conditioned medium and in IGF 1 induced chemotaxis , in comparison to cells before migration . ^^^ When analyzed in vivo , 18 hours after injection of the heterogeneous 5T2 MM population , 5T2 MM cells present in the bone marrow show a higher expression of the IGF 1 receptor than their counterparts before injection . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The susceptibility of PLC for IGF 1 and 2 was restricted by their ability to increase the abundance of inhibitory IGFBPs and to decrease the level of IGF 1 receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The extensive colocalization of insulin receptor ( IR ) and insulin like growth factor 1 receptor ( IGFR ) messenger RNAs during central nervous system development , together with the effects of insulin and IGF 1 in neurogenesis , raises the question of how stage and factor specific signaling occurs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To this purpose , the effects of the LHRH agonist Zoladex ( LHRH A ) on 1 ) the mitogenic action of IGF 1 , 2 ) the tyrosine phosphorylation of type 1 IGF 1 receptor ( IGF IR ) , 3 ) the concentration of IGF IR , and 4 ) the secretion of IGF binding protein 3 were studied . ^^^ The results obtained show that in DU 145 cells , LHRH A 1 ) counteracts the mitogenic action of IGF 1 in a dose dependent manner , 2 ) prevents the IGF 1 induced tyrosine phosphorylation of the IGF IR , 3 ) reduces the concentration of IGF IR without affecting its Kd value , and 4 ) does not affect the secretion of IGF binding protein 3 in the conditioned medium from these cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using in situ hybridization analyses , we determined that IGF 1 , IGF 2 , and IGF IR messenger RNAs were expressed in the highly proliferative terminal end buds during pubertal ductal growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Between 1 7 days post lesion ( dpl ) , in the acute phase following a penetrant wound to the CNS , IGF 2 and IGF IIR protein , but not messenger RNA , were colocalized , with IGF 1 , IGF IR , and IGFBP 1 , 2 , 3 , and 6 , to neurons , macrophages , astrocytes , and microglia within the damaged tissue . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA levels and IGF 1 receptor number both fell . ^^^ In the weanling kidneys , IGF 1 mRNA and peptide levels and IGF 1 receptor binding were unaltered . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA and IGF 1 receptor number and affinity were not different among the four groups . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Northern and Western blotting , and IGF 1 receptor ( IGF IR ) affinity labeling were used to determine the expression of the IGF system , IGFBP levels , and IGF IR levels respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : Immunohistochemical staining of IGF 2 and IGF 1 receptor ( IGF 1R ) was performed on tissue samples of liver metastases from 30 colorectal carcinoma patients . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 , IGF 1 receptor and TGF beta following balloon angioplasty in atherosclerotic and normal rabbit iliac arteries : an immunocytochemical study . ^^^ In this study , we examined the expression of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor , and transforming growth factor beta ( TGF beta ) in atherosclerotic and normal rabbit iliac arteries following overstretch balloon angioplasty of the iliac arteries to create a vascular lesion . ^^^ The iliac arteries were processed for immunocytochemical localization of IGF 1 , IGF 1 receptor and TGF beta using colloidal gold and the data were quantitatively analyzed . ^^^ IGF 1 , IGF 1 receptor and TGF beta immunoreactivity were all significantly increased in atherosclerotic arteries compared to control at all of the time points examined . ^^^ Following balloon angioplasty , the levels of IGF 1 and IGF 1 receptor increased significantly in both control and even further in hypercholesterolemic vessels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Additionally , activation of the IGF 1 receptor in combination with UVB irradiation induced keratinocytes to become post mitotic . ^^^ This survival function of the IGF 1 receptor in response to UVB irradiation was influenced by activation of phosphatidylinositol 3 kinase and MAP kinase . ^^^ Therefore , activation of the IGF 1 receptor in conjunction with UVB irradiation promotes keratinocyte survival at the expense of cell proliferation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In view of decreased expression of transforming growth factor beta 1 ( TGF beta 1 ) , an antagonist of IGF 1 , in endometrial carcinoma , we investigated the expression of IGF 1 , at both the mRNA and protein levels , and the immunoreactivity for type 1 IGF 1 receptor in 30 formalin fixed , paraffin embedded tissue samples of normal and neoplastic endometrium , in order to possibly clarify the role of IGF 1 in endometrial proliferation and differentiation . ^^^ Our results demonstrate a reduced expression of IGF 1 mRNA in endometrial carcinomas compared with non neoplastic tissues , despite equivalent immunohistochemical expression of IGF 1 and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Presumed common evolutionary origin of insulin and IGF 1 receptors and poor ability of lamprey insulin receptor to discriminate between two ligands , implies that lamprey insulin receptor is closer to putative ancestral protein that IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A significant increase in the expression of IGF 1 , IGF 2 , the IGF 1 receptor , and the insulin receptor also was noted . ^^^ Among the embryos that reached the blastocyst stage , the expression of IGF 1 and the IGF 1 receptor also was significantly different in the two study groups . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results suggest that c Src and CSK are involved in IGF IR and IR signaling and that the interaction of CSK with the IGF IR may play a role in the decrease in c Src activity following IGF 1 stimulation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The patient ' s fibroblasts had normal binding of IGF 1 , normal phosphorylation of the beta subunit of IGF 1 receptor ( IGF 1R ) and normal incorporation of thymidine in response to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and IGF 2 signal through a common tyrosine kinase receptor , the insulin like growth factor 1 receptor ( IGF1R ) , and have mitogenic , cell survival , and insulin like actions that are essential for embryogenesis , post natal growth physiology , and breast development . ^^^ Evidence for this statement includes : a ) breast cancers are infiltrated with IGF 2 expressing stromal cells ; b ) mannose 6 phosphate / IGF2 receptor ( M6P / IGF2R ) is mutated in breast cancer , leading to loss of IGF 2 degradation ; c ) IGF1R is overexpressed by malignant breast epithelial cells , and in some cases IGF1R is amplified ; and d ) complex changes in IGF binding protein expression occur during breast cancer progression which most likely also affect IGF 1 and 2 signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , we show that differentiating Schwann cells in the rat sciatic nerve express both the IGF 1 receptor ( IGF 1 R ) and IGF 1 throughout postnatal development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By using an anti IGF 1 specific monoclonal antibody ( mAb ) , we detect surface receptor bound IGF 1 on serum starved DU 145 cells , which activates IGF 1R and triggers a mitogenic signal . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , ETOH treated rats showed a decrease ( p < 0 . 01 ) in the expression of Type 1 IGF receptor mRNA with a subsequent decrease ( p < 0 . 05 ) in the ovarian levels of IGF 1 receptor protein , as determined by Western blot analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
E 2 induced IGF 1 receptor ( IGF 1R ) levels ( as measured by 125I IGF 1 binding and Northern analyses ) in only MCF 7 / 5 23 cells . ^^^ Altered expression of the IGF 1 receptor in a tamoxifen resistant human breast cancer cell line . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , the invasive activity of keloid fibroblasts was markedly increased in the presence of IGF 1 , and inhibited by a neutralizing antibody against IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , we have applied solution hybridization for quantification of the time course for mRNA expression of IGF 1 , IGF 1 receptor , and growth hormone ( GH ) receptor after HI in 7 d old rats . ^^^ There were no changes in IGF 1 receptor mRNA throughout the study period . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Myocardial IGF 1 and IGF 1 receptor ( IGF 1 R ) mRNA were determined by solution hybridization . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the current study , we examined the expression of IGF binding protein 4 ( IGFBP 4 ) , IGF 1 receptor ( IGF IR ) , and IGF 1 in the mouse uterus throughout the estrous cycle . ^^^ They also suggest that IGFBP 4 may play a role in uterine physiology independent of the inhibition of IGF 1 action , and that IGF IR is constitutively expressed in the mouse uterus . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that there is another pathway which regulates PI 3 K and Ras MAPK , independent of the pathway mediated by IGF 1 receptor kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Further , during early bone growth GLUT 4 may be regulated through the IGF 1 receptor rather than via the insulin receptor . ^^^ We propose that skeletal growth retardation in type 1 diabetes may be associated with reduced expression of the GLUT 4 and IGF 1 receptor in the bone growth center . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cardiac ( 23 to 24 % ) and skeletal muscle ( 40 to 62 % ) IGF 1 receptor levels were decreased in adult and old animals with senescence being associated with a further decrease in cardiac IGF 1 receptor levels to 20 % of controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the interactions of ICI 182 , 780 with IGF 1 receptor ( IGF IR ) intracellular signaling have not been characterized . ^^^ The effects of ICI 182 , 780 on IGF IR protein expression were not significant ; however , the drug suppressed IGF 1 induced ( but not basal ) IGF IR tyrosine phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In situ hybridization has been used to study , in the mammary gland of female sheep fetuses , the distribution of mRNA for the mammary mitogens , insulin like growth factor ( IGF ) 1 and IGF 2 , and the IGF 1 receptor , from 10 to 20 weeks of intrauterine life ( term is approximately 22 weeks ) . ^^^ IGF 1 and IGF 2 mRNA were expressed in cells of the intralobular connective tissue underlying the epithelium , while the IGF 1 receptor was expressed in epithelium . ^^^ Quantitation by absorbance measurements showed that mRNA expression increased with pregnancy stage for IGF 1 and IGF 2 , but not significantly for the IGF 1 receptor , and that IGF 2 was more highly expressed than IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
One phosphoramidate , antisense to the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF 1R ) , bound to different proteins than did either a 6 base mismatch phosphoramidate IGF 1R sequence or a sense N ras sequence . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report that both enhanced NO synthesis by ecNOS in afferent arterioles and glomerular endothelial cells and increased expression of IGF 1 receptor can cause glomerular hyperfiltration , and that upregulated expression of ICAM 1 can promote the intraglomerular infiltration of mononuclear cells , which were prevented by aldose reductase inhibitor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) has well characterized mitogenic and antiapoptotic effects in both normal and neoplastic mammary epithelial cells which are mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSIONS : The differential effect of growth hormone treatment on CD4+ and CD8+ lymphocytes might be explained by different expression of the IGF 1 receptor in these distinct subsets . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : All normal tissues expressed IGF 2 , IGF 1 receptor , and IGF II / mannose 6 phosphate ( Man 6 P ) receptor . ^^^ IGF 1 receptor expression was increased by a factor of 2 . 5 and IGF II / Man 6 P receptor by a factor of 4 . ^^^ CONCLUSIONS : This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF 1 receptor and IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , we investigated the potential role of insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) in cell proliferation by overexpressing it in 32D myeloid progenitor cells . ^^^ The overexpression of IGF IR caused the transfectants to proliferate in response to IGF 1 in the absence of insulin receptor substrate ( IRS ) expression . ^^^ Moreover , IGF 1 and / or IL 4 induced long term cell growth of the IGF IR transfectants . ^^^ Finally , we demonstrated that a MAPK kinase inhibitor was able to suppress mitogenesis of the IGF IR transfectants in response to IGF 1 and / or IL 4 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our results suggest that in the case of DNA synthesis the effects of IGF 2 are mediated via the IGF 1 receptor and those of insulin via the insulin receptor , whereas in the case of glycogenesis both are mediated via the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor was uniformly distributed throughout the developing neurite and growth cone in control and IGF 1 treated neurons , but not with high glucose alone . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The steroidogenic effect of both IGFs is mediated through interaction with the IGF 1 receptor , and modified by locally produced IGF binding proteins ( IGFBPs ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 2 , produced by breast cancer epithelial and stromal cells , enhances tumor growth by activating the IGF 1 receptor ( IGF 1 R ) via autocrine and paracrine mechanisms . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of type 1 IGF receptor ( IGF1R ) mRNA , encoding the cognate receptor for both IGF 1 and IGF 2 , as well as type 2 IGF receptor ( IGF2R ) mRNA was not found to be altered during primary prostate cancer progression in intact TRAMP mice but was dramatically reduced in metastatic lesions and in androgen independent disease . ^^^ Together these observations implicate IGF 1 as an important factor during the initiation and progression of primary prostate cancer and provide evidence that there is a strong selection against expression of IGF1R and IGF2R in metastatic and androgen independent disease . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Emerging evidence suggests that members of the IGF family , including IGF 1 , IGF 2 , the IGF 1 receptor ( IGF 1R ) , and the IGF binding proteins ( IGFBPs ) , play important roles in the development and progression of cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) exerts pleiotropic effects on mammalian cells via stimulation of its receptor ( IGF IR ) , a receptor tyrosine kinase . ^^^ In oncological research , IGF 1 has received increased attention as the activated IGF I / IGF IR system displays mitogeneic , transforming , and anti apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The right ventricular ( RV ) and the caval vein IGF 1 mRNA and RV IGF 1 receptor and GH receptor mRNAs were quantitated by means of solution hybridisation assay . ^^^ Two days after shunt opening in SHR , RV and caval vein IGF 1 mRNA increased by 57 % and 108 % ( P < 0 . 05 for both , n=5 6 in each group ) respectively , and these expressions were then turned off , whereas RV GH receptor and IGF 1 receptor mRNA expression remained unaffected compared with WKY rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 swap had a approximately 30 fold loss in affinity for the IGF 1 receptor overexpressed on BHK cells compared with native IGF 1 . ^^^ The parallel increase in dose required to induce negative cooperativity together with the parallel loss in mitogenicity in NIH 3T3 cells implies that disruption of the IGF 1 receptor binding interaction rather than restriction of a post binding conformational change is responsible for the reduction in biological activity of IGF 1 swap . ^^^ Interestingly , the affinity of IGF 1 swap for the insulin receptor was approximately 200 fold lower than that of native IGF 1 indicating that the binding surface complementary to the insulin receptor ( or the ability to attain it ) is disturbed to a greater extent than that to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our findings of normal localization and density of placental IGF IR in FGR encourage us to extend our work to look at the effects of maternal IGF 1 on the transport of glucose and amino acids . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We first determined that endogenous IGFs are directly involved in the recovery process because infusion of an IGF 1 receptor antagonist into the lateral ventricle blocks gradual recovery of limb coordination that spontaneously occurs after partial deafferentation of the olivo cerebellar circuitry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of porcine GH ( pGH ) and IGF 1 as well as the expression of GH ( GHR ) and IGF 1 ( IGF IR ) receptors mRNA were examined . ^^^ The similar action of pGH and IGF 1 on preadipocyte proliferation and differentiation , associated with the similar expression of GHR and IGF IR mRNA in LW and MS pigs , suggests that the GH / IGF 1 axis is not impaired in MS pigs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of the insulin like growth factor 1 receptor ( IGF 1R ) in breast cancer cells : evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF 1 pathway . ^^^ Following addition of dolichyl phosphate to MDA 231 cells , N linked glycosylation of IGF 1R was drastically increased , which in turn was correlated to a substantial translocation of IGF 1R to the plasma membrane , as assayed by IGF 1 binding analysis and by Western blotting of plasma membrane proteins . ^^^ Under normal conditions MDA 231 cells , expressing very few IGF 1R at the cell surface , were not growth arrested by an antibody ( alphaIR 3 ) blocking the binding of IGF 1 to IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and IGF 1 receptor expression was evaluated by immunohistochemistry in both cultured human HSC and human liver tissue . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The possible role of IGF 1 in the regulation of arcuate nucleus synaptic plasticity has been assessed in the present study by intracerebroventricular administration to cycling female rats of a specific IGF 1 receptor antagonist . ^^^ This decline in synaptic inputs and the accompanying increase in glial ensheathing of neuronal somas were blocked by the IGF 1 receptor antagonist . ^^^ In contrast , the IGF 1 receptor antagonist did not affect the basal number of synapses or the morphology of synaptic terminals or length of the synaptic contacts . ^^^ These findings indicate that IGF 1 receptor activation may be involved in the phasic remodeling of arcuate nucleus synapses during the estrous cycle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND & AIMS : We have previously shown that autocrine insulin like growth factor ( IGF ) 2 synthesis through IGF 1 receptor stimulates proliferation and inhibits differentiation of Caco 2 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Exogenous ALA induced the accumulation of substantial concentrations of PpIX in fibrosarcoma cells , and in immortalized fibroblasts transfected with the oncogene c myc , IGF 1 receptor , IGF 1 and its receptor , 5 fos , 5 raf , 5 Ki ras , 5 abl , or polyomavirus middle T antigen with G 418 resistance selection . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor levels were significantly higher in all spinal cord laminae on the side ipsilateral to the immobilized limb than in the same spinal level of the controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis of the IGF 1 receptor ( IGF 1r ) and epidermal growth factor ( EGFr ) in the epidermis of TPA treated HK1 . ^^^ IGF 1 mice to tumor promoters may involve cooperation between the IGF 1r and EGFr signaling pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF IR ) is believed to mediate protective effects of the IGFs against apoptosis . ^^^ To determine whether ceramide mediated induction of apoptosis involved a decreased survival effect of the IGF IR , apoptosis was induced in IGF 1 receptor positive ( R+ ) and negative ( R ) murine fibroblasts by incubation with increasing doses of the sphingolipid analogue , C 2 ceramide . ^^^ Lower ceramide doses were required to induce death in receptor negative compared with receptor positive fibroblasts ( P < 0 . 05 at ceramide doses of 2 microM or greater ) , not only corroborating evidence that the IGF 1 receptor functions as a survival receptor , but also suggesting that ceramide is not inducing apoptosis by suppressing a survival effect of the IGF IR . ^^^ Ceramide also enhanced IGF induced tyrosine phosphorylation of the IGF 1 receptor and activated PI 3 kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed that both IGF 1 Receptor antibody ( IGF 1R alpha ) and IGF 1 Receptor mRNA antisense oligonucleotide had negative effect on tendon cell proliferation ( P < 0 . 01 and P < 0 . 05 ) . ^^^ Under the condition of in vitro culture , several materials including IGF 1 receptor antibody and mRNA antisense oligonucleotide were added to the culture medium to block the IGF 1 Receptor system . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of insulin on protein accumulation and in permitting the TSH effect are reproduced by IGF 1 and are mediated , at least in part by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , these mutant cells showed a higher mitogenic response to IGF 1 than control cells , although IGF 1 receptor expression was similar in both cell lines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated the secretion of insulin like growth factor binding proteins ( IGFBPs ) by estrogen dependent ZR 75 1 and MCF 7 human breast cancer cells , and tamoxifen resistant ( ZR 75 9a1 and LY 2 ) and estrogen independent ( ZR PR LT ) variants which express altered levels of IGF 1 receptor . ^^^ There was no clear correlation between patterns of IGFBP secretion and IGF 1 receptor expression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The growth characteristics of IGF 1R transfectants ( OMIR ) and their response to IGF 1 were then compared with those of OMC in serumless HL 1 cultures . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Almost 90 per cent of haemangiopericytomas expressed IGF 1 receptor ( IGF IR ) mRNA ( 17 out of 19 ) , five ( 26 . 3 per cent ) expressed IGF binding protein 1 ( IGF BP 1 ) , three ( 15 . 8 per cent ) expressed IGF BP 2 , and four ( 21 per cent ) exhibited IGF BP 3 mRNA . ^^^ Binding was much higher in IGF I / IGF IR positive tumours ( 15 . 3+ / 0 . 7 ) than in IGF 1 negative / IGF IR positive tumours ( 5 . 1+ / 3 . 3 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression , purification , and characterization of the cytoplasmic domain of the human IGF 1 receptor using a baculovirus expression system . ^^^ The cytoplasmatic domain of the beta subunit of the human IGF 1 receptor ( residues 929 1337 ) has been overexpressed in insect cells using the baculovirus expression system . ^^^ In contrast , a kinase negative mutant , IGFK K1003A , did not undergo phosphorylation on tyrosine or serine residues , respectively , suggesting that IGF 1 receptor kinase is a dual specific kinase . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In situ hybridization showed that androgen treatment resulted in an increase to 3 fold in insulin like growth factor 1 ( IGF 1 ) and to 5 fold in IGF 1 receptor mRNA in primordial follicle oocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factors ( IGFs ) are capable of blocking apoptosis in many cell lines in vitro , potentially via activation of the IGF 1 receptor ( IGF IR ) . ^^^ Since , unexpectedly , C 2 ceramide was capable of activating MAP kinase , phosphorylating the IGF 1 receptor , and promoting entry into the G 2 phase of the cell cycle , we wished to further determine the mechanisms involved . ^^^ We also demonstrate that in the presence of sodium orthovanadate , ceramide induced death is increased , and the phosphorylation of a 75 kDa protein which associates with the IGF 1 receptor is enhanced . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To assess the influence of this growth factor family on demyelination and repair in multiple sclerosis ( MS ) , the expression of IGF 1 , IGF 2 , insulin , IGF binding proteins ( IGFBP ) 1 3 and IGF 1 receptor ( IGF IR ) in CNS tissue from MS and normal control cases was studied by immunocytochemistry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have previously demonstrated that VDRCs antagonize the growth promoting activity of IGF 1 by stimulating autocrine production of IGFBP 5 in MCF 7 cells , but the effect of VDRCs on IGF 1 receptor ( IGF IR ) intracellular signaling has not been elucidated . ^^^ We report here that the vitamin D analogue EB 1089 interferes with the IGF IR signaling pathway by attenuating IGF 1 induced tyrosine phosphorylation of IRS 1 , and to a lesser extent , IRS 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : IGF 1 , IGF 1 receptor and IGF binding proteins ( IGFBPs ) are expressed in thyroid tissue and are associated with the function and growth of the thyroid . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) immunoreactivity in normal and osteopetrotic ( toothless , tl / tl ) rat tibia . ^^^ This study examined the immunohistochemical distribution of IGF 1 and IGF 1 receptor ( IGF IR ) in tibias from normal and osteopetrotic ( toothless , tl / tl ) rats , following treatment with colony stimulating factor 1 ( CSF 1 ) . ^^^ In normal rats , immunoreactivity for IGF 1 and IGF IR was detected in cells of the articular and epiphyseal cartilage , secondary ossification centres , zones of resting and proliferating chondrocytes and bone marrow . ^^^ Bone marrow cells immunoreactive for IGF 1 and IGF IR were significantly reduced in the tl / tl rat ( p < 0 . 001 ) compared with normal animals . ^^^ Treatment of tl / tl rats with CSF 1 increased immunoreactivity for IGF 1 and IGF IR in bone marrow cells as well as the number of TRAP positive osteoclasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
With the methods of immunohistochemical study and flow cytometric study , the density of IGF 1 receptor of the primary , 6th and 13th generation of tendon cell was analyzed . ^^^ However , in the cell cycle , the numbers of IGF 1 receptor in G2M phase tendon cells were more than that in G 1 phase cells ( P < 0 . 01 ) . ^^^ These works provided sufficient evident which suggested there were stable density of IGF 1 receptor on the tendon cell though out the life span of tendon cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated the role of IGF 1 receptor ( IGF IR ) signaling in locomotion of MCF 7 breast cancer epithelial cells overexpressing the wild type IGF IR ( MCF 7 / IGF IR ) . ^^^ Stimulation of MCF 7 / IGF IR cells with 50 ng / ml IGF 1 induced disruption of the polarized cell monolayer followed by morphological transition toward a mesenchymal phenotype . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Assay for IGF 1 receptor binding capacity revealed that 70 % of the total receptor binding capacity could be recovered in the plasma membrane fraction isolated from the beads as compared with the receptor binding capacity of intact cells , demonstrating the functional integrity of the isolated membranes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These experiments indicate that TNF alpha promotes IGF 1 receptor resistance in neurons and inhibits the ability of the IGF 1 receptor to tyrosine phosphorylate the IRS 2 docking molecule and to subsequently activate the critical downstream enzyme phosphatidylinositol 3 ' kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) stimulates multiplication of the human osteosarcoma cell line , MG 63 , by acting through IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Grb 10 has been described as a cellular partner of several receptor tyrosine kinases , including the insulin receptor ( IR ) and the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This decrease in bioavailable IGF 2 ultimately resulted in diminished IGF 1 receptor signaling in vivo as evidenced by diminished receptor kinase activity and decreased tyrosine phosphorylation of the IGF 1 receptor downstream effectors , insulin receptor substrate 1 ( IRS 1 ) , extracellular signal regulatory kinase ( Erk ) 1 , and Erk 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The inappropriate expressions of insulin like growth factors ( IGF 1 and 2 ) and IGF 1 receptor ( IGF IR ) are implicated in the malignant growth of many cancers . ^^^ To determine changes , if any , in the levels of expression of IGFs and IGF receptor genes in neoplastic endometrium , relative to normal endometrium , the mRNA levels of IGF 1 and 2 and of IGF IR and IIR were measured in samples of endometrial carcinomas ( EC ) and normal endometrium , through all phases of the menstrual cycle , by semiquantitative reverse transcription polymerase chain reaction ( RT PCR ) assays . ^^^ A positive correlation between the levels of IGF 1 and IGF IR mRNAs , apparent in the samples of normal endometrium , was not observed in endometrial carcinomas . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined IGF 1 and IGF 1 receptor ( IGF 1R ) gene expression in a single blastomere of an early mouse embryo and compared it with subsequent embryo development in culture . ^^^ Individual blastomeres from each embryo were then assayed for the presence of IGF 1 and IGF 1R mRNA using reverse transcription polymerase chain reaction . ^^^ IGF 1R gene expression was detected in the majority of embryos tested and IGF 1 gene expression was detected in 34 of 81 ( 42 % ) embryos . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of the IGF 1 receptor in the growth and transformation of mammalian cells . ^^^ Although cells homozygous for a targeted disruption of the IGF 1 receptor genes can grow in serum supplemented medium , the IGF 1 receptor is required for optimal growth , and is required equally in all phases of the cell cycle . ^^^ The expression of both the IGF 1 receptor and its ligands is regulated by other growth factors ( especially PDGF and EGF ) , by oncogenes ( like SV 40 T antigen and c myb ) and by tumour suppressor genes ( like WT 1 and RB ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study the effect of androgens on ovarian insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor gene expression was investigated . ^^^ Likewise , both androgens induced significant increases in the amount of IGF 1 receptor mRNA , most notably in thecal cells and less markedly in granulosa and interstitium ( P < 0 . 05 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that ( 1 ) specific binding sites for IGF 1 are present in the newt testes , ( 2 ) IGF 2 and insulin also bind to these receptors but to a lesser degree , and ( 3 ) IGF 2 and insulin as well as IGF 1 promote spermatogonial differentiation into primary spermatocytes by binding to the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine the local mechanisms involved in the effects of skeletal unloading on bone formation , we studied the temporal pattern of mRNA levels for insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor type 1 ( IGF IR ) , and transforming growth factor beta receptor type 2 ( TGF betaRII ) in relation to osteoblast phenotypic markers and osteoblast activity in hindlimb suspended rats . ^^^ Unloading also decreased mRNA levels for IGF 1 , IGF IR , and TGF betaRII at 4 7 days in the metaphyseal bone . ^^^ However , IGF 1 and IGF IR levels rose above normal at 14 days of suspension . ^^^ The associated biphasic pattern of IGF I / IGF IR expression , osteoblast markers , and osteoblast activity strongly suggests an important role for IGF 1 signaling in the local effect of skeletal unloading on metaphyseal bone formation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To establish a role for the Igf 1 receptor in beta cells , we intercrossed mice heterozygous for null alleles of Igf1r and Irs 2 . ^^^ Irs 2 coordinates Igf 1 receptor mediated beta cell development and peripheral insulin signalling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have examined the mechanism by which collagen binding integrins co operate with insulin like growth factor 1 ( IGF 1 ) receptors ( IGF IR ) to regulate chondrocyte phenotype and differentiation . ^^^ Moreover , exposure of collagen type 2 cultured chondrocytes to IGF 1 leads to co immunoprecipitation of Shc protein with the IGF IR and with beta 1 , alpha 1 and alpha 5 integrins , but not with alpha 3 integrin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mRNA was found to be detectable throughout the gastrointestinal mucosa and in the intestinal epithelial cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSIONS : These results suggest that the mitogenic effects of insulin and glucose on infragenicular VSMC are due to stimulation of the IGF 1 receptor . ^^^ VSMC antiproliferative strategies employing receptor blockade should be directed against the IGF 1 receptor , not the insulin receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , cell resistance to IGF 1 occurred at a step distal to IGF 1 receptors ( IGF IRs ) , as AIRs altered neither IGF 1 binding nor IGF 1 induced IGF IR autophosphorylation , but inhibited the ability of IGF IRs to mediate tyrosine phosphorylation of IRS 1 and IRS 2 in response to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor blocking antibody ( IGF IRBAb ) blocked the proliferative effect of tIGF 1 but not that to tIGF 2 . ^^^ Estrogen related proliferation in ROS17 / 2 . 8 cells appears to be mediated by IGF 1 acting through the IGF 1 receptor and does not involve IGF 2 . ^^^ In contrast , strain related proliferation appears to be mediated by IGF 2 and does not involve either IGF 1 or the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The analysis on IGF 1 receptor mRNA was significantly lowered in GH producing adenoma compared with the other types of adenoma . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Changes in IGF 1 receptor messenger RNA levels are reflected in cell surface receptor number , and modulation of IGF 1 receptor levels affects tumorigenicity in numerous cellular models ; thus , control of IGF 1 receptor gene expression appears to be an important level at which cellular proliferation and tumorigenic potential may be regulated . ^^^ We have previously shown that the product of the WT 1 Wilms ' tumor suppressor gene represses IGF 1 receptor gene expression both in vitro and in vivo , and that decreased WT 1 levels are correlated with up regulation of IGF 1 receptor gene expression in Wilms ' tumor , benign prostatic hyperplasia , and breast cancer . ^^^ In this report , we analyze the relative activity of wild type and mutant versions of the WT 1 protein with respect to IGF 1 receptor promoter activity in transient transfection assays and assess the potential contribution of WT 1 self association to IGF 1 receptor regulation using the yeast two hybrid system . ^^^ Of the naturally occurring variations in WT 1 structure , only the presence of a three amino acid KTS insert in the zinc finger domain introduced by alternative splicing of exon 9 had a significant effect on WT 1 repression of IGF 1 receptor promoter activity . ^^^ Our results suggest that 1 ) the DNA binding capacity of WT 1 is critical for maximal repression of the IGF 1 receptor promoter , but some effects may be mediated through protein protein interactions involving the N terminal domain ; 2 ) WT 1 self association may not be required for repression of the IGF 1 receptor promoter ; and 3 ) the Denys Drash syndrome version of the WT 1 protein may exhibit residual or possible gain of function activity in some contexts rather than exerting dominant negative effects , as has been proposed previously . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
TPN without growth factor treatment ( TPN control ) induced jejunal atrophy , reduced serum IGF 1 , increased serum insulin concentrations , and increased IGF 1 receptor number , IGF 1 receptor messenger RNA , and insulin specific binding to 133 % to 170 % of the orally fed reference values , P < 0 . 01 . ^^^ Compared with TPN control , IGF 1 or IGF 1 + GH stimulated jejunal mucosal hyperplasia ; IGF 1 treatment increased serum IGF 1 by 2 to 3 fold and decreased serum insulin concentrations by 60 % , decreased IGF 1 receptor number by 50 % ( P < 0 . 001 ) , and increased insulin receptor affinity and insulin receptor protein content . ^^^ We conclude that : 1 ) jejunal IGF 1 receptor content reflects circulating concentration of ligand and is not limiting for jejunal growth ; and 2 ) increased circulating concentration of IGF 1 may promote jejunal growth via interaction with jejunal insulin or IGF 1 receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Although the EGF receptor was decreased 20 hours after injury , the lack of IGF 1 effect could not be explained by loss of the IGF 1 receptor , which remained unchanged after peroxide injury . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The localization of mRNAs for insulin like growth factors 1 ( IGF 1 ) and 2 ( IGF 2 ) and the type 1 IGF receptor ( IGF 1R ) in bovine follicles and corpora lutea was determined using in situ hybridization on sectioned ovaries collected from nonpregnant , cyclic Holstein cows in either the follicular ( n = 3 ) or luteal ( n = 5 ) phases of the cycle . ^^^ In the remaining 17 % of follicles , expression was very low and was unrelated to size or state of atresia . mRNAs encoding IGF 1 , 2 and IGF 1R were all present in the corpus luteum , whereas only those for IGF 2 and IGF 1R were found in ovarian stroma . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , neutralizing antibody to TGF beta or to IGF 1 receptor did not suppress increases in laminin C 1 promoter activity induced by culture of stable integrants in high glucose . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Testosterone was administered to peripubertal rats and the responses of mRNA of GH receptor , IGF 1 , IGF 1 receptor and IGF binding proteins 1 and 3 ( IGFBP 1 and IGFBP 3 ) as well as circulating IGF 1 were evaluated in two time related models : over 12 h after a single injection ( short term study ) and 10 days after continuous administration ( long term study ) . ^^^ In the EGP , neither testosterone administration nor hypophysectomy had any effect on IGF 1 and IGF 1 receptor mRNA levels . ^^^ These data suggest that the effect of testosterone on growth ( as assessed by weight gain ) is small and is not mediated by changes in hepatic gene expression of IGF 1 , IGF 1 receptor , IGFBP 1 , IGFBP 3 or circulating IGF 1 . ^^^ At the EGP , the testosterone effect on linear growth is not mediated through changes in mRNA abundance of IGF 1 and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The wild type insulin receptor chimera mediated approximately 2 fold greater phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , association of IRS 1 with phosphoinositide 3 kinase , stimulation of glucose uptake , and GLUT 4 translocation , compared with the IGF 1 receptor chimera . ^^^ In contrast , the IGF 1 receptor chimera mediated more effective Shc phosphorylation , association of Shc with Grb 2 , and activation of mitogen activated protein kinase compared with the insulin receptor chimera . ^^^ We conclude that the insulin receptor mediates some aspects of metabolic signaling in adipocytes more effectively than the IGF 1 receptor , as a consequence of more efficient phosphorylation of IRS 1 and greater recruitment / activation of phosphoinositide 3 kinase . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Placental anionic and cationic amino acid transporter expression in growth hormone overexpressing and null IGF 2 or null IGF 1 receptor mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of IGF 1 enhanced cellular proliferation in cells overexpressing the IGF 1 receptor alone but had an even greater proliferative effect in cells overexpressing both the IGF 1 receptors and IRS 4 . ^^^ These results suggest that IRS 4 is implicated in the IGF 1 receptor mitogenic signaling pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , if the IGF 1 receptor ( IGF IR ) is even modestly overexpressed , then IGF 1 , by itself , stimulates the growth of MEFs in monolayer and makes them capable of forming colonies in soft agar . ^^^ GEP activates , in R cells , the two signaling pathways that are known to be sufficient for IGF 1 mediated mitogenesis in cells overexpressing the IGF IR , the mitogen activated protein kinase and the phosphatidylinositol 3 kinase pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since the IGF 1 receptor has tyrosine kinase activity and its ligand IGF 1 is present in the seminal plasma , the IGF 1 system ( IGF 1R / IGF 1 / IGF binding protein ) may be involved in the signal transduction pathway leading to sperm capacitation and acrosome exocytosis . . ^^^ These data indicate that the IGF 1 receptor is present in the human sperm cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Induction of tumor suppression and glandular differentiation of A 549 lung carcinoma cells by dominant negative IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF IR ) mRNA was induced 2 . 1 fold in Ang 2 rats compared with ad libitum fed rats ( P < 0 . 01 ) . ^^^ In conclusion , autocrine upregulation of cardiac IGF 1 and IGF IR mRNA by Ang 2 occurs through hemodynamic and nonhemodynamic mechanisms , respectively , and may modulate cardiac structural changes that occur in hypertension . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To further characterize the regulatory role of the IGF system on GnRH neuronal function , we have examined the gene expression of IGF 1 , IGF 2 , IGF 1 receptor ( IGF IR ) , and IGF binding proteins ( IGFBPs ) in a GnRH neuronal cell line ( GT 1 7 cells ) . ^^^ RT PCR analysis demonstrated IGF 1 , IGF 2 and IGF IR mRNAs in GT 1 7 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study examines the hypotheses that the luteolytic actions of prostaglandin F ( 2alpha ) ( PGF ( 2alpha ) ) during the early luteal phase may involve either a decrease in IGF 1 or IGF receptor ( IGF IR ) , or an increase in IGF binding protein ( IGFBP ) 3 , expression , any of which could interfere with the luteotropic actions of IGF 1 in this tissue . ^^^ By slot blot analysis , steady state levels of IGF 1 and IGFBP 3 mRNA were not different in PGF ( 2alpha ) treated vs . control animals ; however , IGF IR mRNA was increased in treated animals on Day 9 . ^^^ In conclusion , PGF ( 2alpha ) induced premature luteolysis was associated with an increase in steady state levels of IGF IR mRNA , but it did not appear to be linked to changes in mRNA levels for IGF 1 or IGFBP 3 . ^^^ However , since IGFBP 2 and 3 protein levels increased early in the treatment period ( Days 6 7 ) , it is possible that they may mediate the luteolytic actions of PGF ( 2alpha ) by sequestering IGF 1 and preventing its interaction with the IGF IR . . ^^^ Insulin like growth factor ( IGF ) 1 , IGF 1 receptor , and IGF binding protein 3 messenger ribonucleic acids and protein in corpora lutea from prostaglandin F ( 2alpha ) treated gilts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Myocardial glut 1 , glut 4 , insulin receptor ( Ins R ) and insulin like growth factor 1 receptor ( IGF 1 R ) protein levels were unaffected by 36 weeks of chronic exercise . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) dependent activation of pp42 / 44 mitogen activated protein kinase occurs independently of IGF 1 receptor kinase activation and IRS 1 tyrosine phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To analyse whether this effect is mediated through estrogen receptors and through cross talk between steroid and insulin like growth factor ( IGF ) systems , we have concomitantly administered antagonists of estrogen receptor ( ICI 182 , 780 ) or the IGF 1 receptor ( JB 1 ) with estradiol . ^^^ In conclusion , an interaction of estrogen receptor and IGF 1 receptor signalling may mediate neuroprotection in the adult rat hippocampus . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Southern blotting revealed a 50 % reduction in IGF 1 receptor DNA , and in an RNase protection assay ( RPA ) , a quantitatively similar reduction in steady state mRNA for type 1 IGF receptor . rhIGF 1 was administered in graded doses of 40 , 60 and 80 microg / kg twice daily by subcutaneous injection for periods of 2 2 . 5 days each . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , the constructs with the first three domains of the IGFIR had high specificity , the affinity of the novel minimized IGFIR for IGFI was 1 . 5 nM , whereas the affinity for insulin was more than 3000 nM . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ontogeny of the insulin like growth factor system ( IGF 1 , IGF 2 , and IGF 1R ) in gilthead seabream ( Sparus aurata ) : expression and cellular localization . ^^^ Transcripts for IGF 1 , IGF 2 , and IGF 1R were detected throughout development in unfertilized eggs , embryos , and larvae , suggesting that these mRNAs are products of both the maternal and the embryonic genomes . ^^^ The distribution of the two types of IGF 1R and IGF 1 in gilthead seabream larvae was studied by immunohistochemistry and found to be tissue specific and age dependent . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Most of insulin ' s effects occur by way of the IGF 1 receptor as a two fold stimulation of GFA activity was seen with significantly lower doses ( 10 ng / ml ) of IGF 1 . ^^^ We conclude that GFA enzyme activity is upregulated by insulin and this may occur via a IGF 1 receptor mediated pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Rapid induction of IGFBPs , which can limit access of insulin like growth factors ( IGFs ) to the IGF 1 receptor , may play a role in the induction of apoptosis by antiandrogens , particularly in view of the increasing evidence that IGF 1 inhibits apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Heightened tyrosine phosphorylation of IRS 2 during granulocytic differentiation was not caused by an increase in expression of the tyrosine kinase IGF 1 receptor , as measured by the amount of both the alpha and beta subunits . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Overexpression of PC 1 in MCF 7 cells inhibited tyrosine kinase activity of the IR , but not of the IGF 1 receptor . ^^^ In contrast , after specific immunocapture , PC 1 was not associated with the IGF 1 receptor . ^^^ In contrast , IGF 1 receptor tyrosine kinase activity was not increased . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mitogenic and chemotactic actions of IGF 1 are mediated through the IGF 1 receptor , but how the activation of the IGF 1 receptor leads to these biological responses is poorly understood . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
After interleukin 3 withdrawal or etoposide treatment , exogenous IGF 1 prevented apoptosis and elevated levels of Cdc 2 , a biochemical indicator of a functional IGF 1 receptor pathway . ^^^ Furthermore , IGF 1 receptor overexpression failed to protect cells against SC alphaalphadelta 9 induced apoptosis . ^^^ Kinetic analyses demonstrated that Cdc 2 down regulation after SC alphaalphadelta 9 treatment preceded both apoptosis and loss of the IGF 1 receptor , indicating that loss of Cdc 2 was a direct effect of SC alphaalphadelta 9 treatment and not secondary to cell death . ^^^ IGF 1 receptor autophosphorylation studies indicated that SC alphaalphadelta 9 did not interact directly with the IGF 1 receptor nor bind to the growth factor itself , suggesting a site of action distal to the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PSM / SH2 B has been described as a cellular partner of the FcepsilonRI receptor , insulin receptor ( IR ) , insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) , and nerve growth factor receptor ( TrkA ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNA transcript of the IGF 1 receptor was not detected in oviduct epithelial cells , but a prominent band corresponding to the insulin receptor was observed . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect is mediated via the type 1 IGF 1 receptor ( IGF IR ) , which is essential for growth in these cells . ^^^ These effects of IGF 1 were blocked by a neutralizing antibody against IGF IR ( alpha IR 3 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Further , this region is located on the opposite surface of IGF 1 from putative type 1 receptor binding residues , allowing the possibility that the antiserum might be able to modulate IGF 1 receptor binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Interestingly , the addition of an anti IGF 1 receptor ( IGF 1R ) antibody to the organ cultures maintained in high Ca2+ medium induced changes reminiscent of those seen when the organ cultures were maintained in low Ca2+ medium , i . e . tissue degeneration . ^^^ In cultured human keratinocytes , anti IGF 1R antibody partially inhibited the IGF 1 mediated stimulation of human keratinocyte proliferation without affecting normal spontaneous growth . ^^^ Additionally , IGF 1R immunolocalized to basal keratinocytes in vivo , exhibited specific binding to IGF 1 in vitro . ^^^ Messenger RNA encoding both IGF 1 and IGF 1R were readily detected by RT PCR in organ cultures incubated in both low and high Ca2+ medium . ^^^ There were no detectable differences in IGF 1 mRNA in organ cultures growing in the low or high Ca2+ medium , but lower levels of IGF 1R mRNA were observed in the organ cultures maintained in low Ca2+ medium than in those in high Ca2+ medium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The latter control IGF transport , efflux from vascular compartments and association with cell surface receptors . [ 4 ] In tissues , IGF 1 is produced by mesenchymal type cells and acts in a paracrine and autocrine fashion by binding to the IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Stimulation of DAOY cells by IGF 1 led to phosphorylation of its cognate receptor ( IGF IR ) and resulted in cell proliferation . ^^^ These effects of IGF 1 were suppressed by IGF IR blocking antibodies and by PD 98059 , MAP kinase pathway inhibitor . ^^^ The results demonstrate the existence of an autocrine IGF I / IGF IR loop and indicate that IGF 1 promotes proliferation via MAP kinase pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To address the issue of molecular genetic events that participate in genesis and progression of hemangiopericytoma we analyzed insulin like growth factor ( IGF ) 2 and IGF 1 receptor in 29 tumors collected from a human tumor bank network . ^^^ Of 22 tumors tested 12 ( 54 . 5 % ) exhibited IGF 2 mRNA , while almost 90 % ( 17 of 19 ) of hemangiopericytomas exhibited IGF 1 receptor mRNA . ^^^ Simultaneous administration of antisense deoxyoligonucleotides to both IGF 2 and IGF 1 receptor inhibited tumor cell proliferation by even 80 % . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Also associated with the mitogenic growth in the adult female were significant 2 to 4 fold increases in remnant kidney IGF 1 receptor gene expression , which occurred in the presence and absence of pulsatile GH secretion . ^^^ Thus , in female rats , the initial phase of CRG is GH independent , but is associated with significant increases in remnant kidney IGF 1 receptor gene expression and hyperplastic renal growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These interactions may be important for concentrating intact IGFBP 5 in extracellular matrix and for modulating the cooperative interaction between the IGF 1 receptor and integrin receptor signaling pathways . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , IGF 1R , M6P / IGF 2R genes are expressed in the thymus both in fetal and postnatal life , whereas IGF 2 messenger RNAs ( mRNAs ) decline after birth but are still detectable on the seventh week . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : Activation of the insulin like growth factor 1 receptor ( IGF IR ) by its ligands IGF 1 and IGF 2 induces cell proliferation and protects against apoptosis . ^^^ RESULTS : There was considerable variability in the ability of ethanol to inhibit IGF 1 dependent IGF IR tyrosine autophosphorylation and MAP kinase activation , despite equivalent IGF IR expression . ^^^ The sensitivity of IGF IR autophosphorylation to ethanol correlated directly with the inhibition of IGF 1 mediated MAP kinase activation and cell proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both alphaIR 3 , a neutralizing monoclonal antibody to the IGF 1 receptor , and JB 1 , an IGF 1 analogue antagonist , attenuated the stimulatory effects of T 3 . ^^^ T 3 effects also were decreased in cells transfected with antisense oligonucleotide ( AS ODN ) to the IGF 1 receptor gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of insulin like growth factor 1 receptor ( IGF 1R ) and p27Kip1 in melanocytic tumors : a potential regulatory role of IGF 1 pathway in distribution of p27Kip1 between different cyclins . ^^^ To analyze whether there is a causative relationship between the IGF 1 pathway and p27Kip1 expression , melanoma cells were treated with alpha IR 3 , an antibody blocking the IGF 1 binding to IGF 1R , or Tunicamycin , which inhibits the translocation of IGF 1R to the cell surface . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When plasma levels of insulin and IGF 1 were decreased by fasting , insulin receptor numbers fell 3 . 6 fold and IGF 1 receptor numbers fell 2 . 2 fold . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The specificity determinants for IGF 1 binding are known to be located in the cysteine rich ( Cys rich ) region between residues 223 and 274 of human IGF 1R , which includes a loop that protrudes into the putative ligand binding site . ^^^ Properties of an insulin receptor with an IGF 1 receptor loop exchange in the cysteine rich region . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since IGF expression in avian species is less well documented , we studied here the expression of IGF 1 and IGF 2 during chicken CNS development , using in situ hybridization and reverse transcriptase PCR , and compared the results with the expression of the IGF type 1 receptor ( IGF 1R ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The arrangement of the L 1 and S 1 domains of the model are similar to that of the first two domains of the IGF 1 receptor , whereas that of the L 2 and S 2 domains appear to be significantly different . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 inhibits the progression of human U 2 OS osteosarcoma cells towards programmed cell death through interaction with the IGF 1 receptor . ^^^ Co incubation with an IGF 1 receptor monoclonal antibody ( alphaIR 3 ) dose dependently blocked the effects of 10 ng / ml IGF 1 on PCD , with an ED 50 of 1 10 ng / ml of alphaIR 3 immunoglobulin . ^^^ In summary , IGF 1 treatment of U 2 OS cells at the same time inhibits the induced programmed cell death and increases the cell number , effects which are blocked by addition of IGF 1 receptor antibodies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that STAT 3 , but not STAT 5 , was activated in response to IGF 1 in 293T cells cotransfected with IGF IR and STAT expression vectors . ^^^ Moreover , tyrosine phosphorylation of STAT 3 , JAK 1 , and JAK 2 was increased upon IGF 1 stimulation of endogenous IGF IR in 293T cells transfected with the respective STAT or JAK expression vector . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Phenotypic changes observed in skin were associated with transgene expression in the basal layer of the epidermis and activation of the IGF 1 receptor . ^^^ These data suggest that persistent activation of IGF 1 receptor signaling pathways in basal epithelial cells leads to spontaneous tumor promotion and that up regulation of both mitogenic and cell survival signaling pathways may play an important role in the action of IGF 1 in this model system . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the coupling between the signaling cascades of estrogen receptors alpha and beta and the IGF 1 receptor ( IGF 1R ) is poorly understood . ^^^ Estrogen receptor alpha rapidly activates the IGF 1 receptor pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We will focus on the mechanisms that determine signalling specificity by the receptor tyrosine kinases , especially the insulin receptor and the type 1 insulin like growth factor receptors ( IGF 1 receptor ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Death could be prevented by IGF analogues that activated the IGF 1 receptor or by unrelated growth factors such as platelet derived growth factor BB ( PDGF BB ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CD 28 stimulation increases IGF IR expression on Jurkat cells , and exogenously added IGF 1 can protect these cells from Fas induced apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Time will tell what the practical relevance of these findings is and what the clinical features of the new mutations are ; we will probably learn something more about the GHRH GH IGF 1 axis : to date , no mutations have been reported regarding the GHRH gene or the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) is an important regulator of many aspects of growth , differentiation , and development , and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life , we considered the genes encoding the IGF 1 and the IGF 1 receptor ( IGF IR ) as candidates for low birth weight , insulin resistance , and type 2 diabetes . ^^^ Here we report the mutational analysis of the coding regions of the IGF 1 and IGF IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families . ^^^ No mutations predicting changes in the amino acid sequences of the IGF 1 or IGF IR genes were detected , but several silent and intronic polymorphisms were found . ^^^ In conclusion , variability in the coding regions of IGF 1 and the IGF IR does not associate with reduced birth weight , insulin sensitivity index , or type 2 diabetes in the Danish population . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The purpose of this study was to determine the effects of aging and caloric restriction ( CR ) on insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor ( IGF IR ) , IGF binding protein 3 ( IGFBP 3 ) and IGFBP 4 expression in the stomach and colon of male Fischer 344 rats . ^^^ Because the aging colon has a propensity to develop cancer , it may adapt to increased colonic IGF 1 expression by reducing IGF IR and IGFBP 3 expression . ^^^ Effects of aging and caloric restriction on IGF 1 , IGF 1 receptor , IGFBP 3 and IGFBP 4 gene expression in the rat stomach and colon . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Treatment with insulin or IGF 1 for 4 h increased the abundance of VEGF mRNA in NIH3T3 fibroblasts expressing either the human insulin receptor ( NIH IR ) or the human IGF 1 receptor ( NIH IGFR ) by 6 and 8 fold , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using RNAase protection analysis ( RPA ) , we examined the gene expression for IGF 1 , IGF 2 , IGF1R , M6P / IGF2R , IGFBP 1 and IGFBP 2 in a series of hepatoblastomas with corresponding normal liver from the same individuals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Angiotensin 2 reduces circulating and skeletal muscle IGF 1 but increases IGF 1 and the IGF IR expression in cardiac muscle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis of mammary gland development in knockout mice which are deficient in IGF 1 or the IGF 1 receptor supports the conclusion that the IGF system is important for normal mammary gland development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Examination of the IGF IR during the mammary gland lactation cycle shows that IGF IR number declines at parturition , a change that coincides with decreases in the blood level of its ligand , IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These effects were not associated with changes in the number or affinity of IGF 1 receptors , but with an increase in membrane associated IGF binding proteins , which were previously shown in different cancer cells to negatively regulate IGF 1 receptor activation . ^^^ Collectively , the above data suggest that the inhibitory effects of lycopene on MCF 7 cell growth are not due to the toxicity of the carotenoid but , rather , to interference in IGF 1 receptor signaling and cell cycle progression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Antagonists of the IGF 1 receptor , IGF 1 Analog or monoclonal antibody 1H7 , elicited concentration dependent inhibition of growth and decrease in IGFBP 3 , IGFBP 4 , and IGFBP 5 production , implying that endogenous IGF 1 stimulated growth and IGFBP production . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We hypothesized that inhibition of IGF 1 receptor expression in the psoriasis lesion would reverse psoriatic epidermal hyperplasia by slowing the rate of keratinocyte cell division . ^^^ Here we report the use of C 5 propynyl dU , dC phosphorothioate antisense oligonucleotides to inhibit IGF 1 receptor expression in keratinocytes . ^^^ We identified several inhibitory antisense oligonucleotides and demonstrated IGF 1 receptor inhibition in vitro through an mRNA targeting mechanism . ^^^ The findings indicate that IGF 1 receptor stimulation is a rate limiting step in psoriatic epidermal hyperplasia and that IGF 1 receptor targeting by cutaneous administration of antisense oligonucleotides forms the basis of a potential new psoriasis therapy . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have examined the role of cross talk between the IGF 1 receptor ( IGF 1R ) and the epidermal growth factor receptor ( EGFR ) in mediating responses to IGF 1 . ^^^ In COS 7 cells , IGF 1 stimulation causes tyrosine phosphorylation of the IGF 1R beta subunit , the EGFR , insulin receptor substrate 1 ( IRS 1 ) , and the Shc adapter protein . ^^^ Shc immunoprecipitates performed after IGF 1 stimulation contain coprecipitated EGFR , suggesting that IGF 1R activation induces the assembly of EGFR . ^^^ Tyrphostin AG 1478 , an inhibitor of the EGFR kinase , markedly attenuates IGF 1 stimulated phosphorylation of EGFR , Shc , and ERK1 / 2 but has no effect on phosphorylation of IGF 1R , IRS 1 , and protein kinase B ( Akt ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Protein metabolism in hind limb skeletal muscle was studied by incorporation of L [ 14C U ] phenylalanine into proteins , western blot determination of translation initiation factors involved in the binding of the 40S ribosomal subunit to mRNA , and quantification of mRNA content for IGF 1 , IGF IR and GH R . ^^^ Muscle content of IGF 1 mRNA was reduced in semi starved animals , whereas IGF 1 receptor mRNA was unaltered despite food restriction . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF peptides ( IGF 1 and 2 ) mediate their effects through the type 1 IGF receptor ( IGF 1R ) , while the IGF binding proteins ( IGFBP 1 to 6 ) modulate their interaction with the receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , only the internalization of the IGF 1 receptor complex was blocked by an inhibitor of phosphotyrosylation . ^^^ Science , 284 , 974 977 ] suggests that a similar strategy could be used for IGF 1 and the IGF 1 receptor leading to the characterization of IGF 1 mimics of potential clinical usefulness . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tumour cells often have enhanced survival mechanisms due either to up regulation of the IGF 1 receptor and its ligands or to loss of function of a phosphatase ( PTEN ) that regulates part of this survival pathway . ^^^ The C terminus of the IGF 1 receptor appears to be a regulatory domain for the anti apoptotic activity of this receptor , and certain residues within the C terminus are essential for this regulatory activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study was undertaken to determine whether the augmentation by cAMP of IGF 1 dependent tyrosine phosphorylation of known IGF 1 receptor substrates plays an important role in the cAMP dependent potentiation of DNA synthesis induced by IGF 1 . ^^^ These effects are mediated by changes in tyrosine phosphorylation of IGF 1 receptor substrates , including IRS 2 and Shc . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In parallel , IGF 1 activates IGF 1 receptor , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 ( PI 3 ) kinase , and FAK . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the contrary , IGF 2 mRNA transcribed from the fetal or fetal neonatal IGF 2 promoter and IGF 1 receptor mRNA ( both used as hybridization control ) were both found in whole pre menopausal ovary and luteinized granulosa cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recognizing its homology with Insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) and the critical role of IGF 1 in neuronal survival , we hypothesized that AATYK plays an important role in neuronal differentiation / apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Accordingly , we undertook this study to ascertain whether diabetes impairs the healing process by suppressing the wound microenvironmental IGF 1 system ( eg , IGF 1 ; IGF 1 receptor [ IGF 1 R ] ; and IGF 1 binding protein [ IGF BP ( 3 ) ] ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To test whether hormonal regulation of IGF 1 receptor ( IGF IR ) and IGF binding protein 2 ( IGFBP 2 ) may be involved in the accumulation of IGF 1 in tanycytes , we assessed the effect of ovarian hormones on the levels of these molecules in the mediobasal hypothalamus of adult female rats . ^^^ These results do not support the hypothesis that estrogen induced accumulation of IGF 1 by tanycytes is mediated by the hormonal regulation of IGF IR . ^^^ However , estrogen induced up regulation of IGFBP 2 and progesterone induced down regulation of IGF IR and IGFBP 2 levels in the apical plasma membrane of tanycytes may be involved in the fluctuation of IGF 1 levels in the mediobasal hypothalamus during the estrous cycle . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Hence , even though half the maximum dosage required for the insulin effect was rather high ( between 0 . 1 and > 5 micro g ) , the effect of insulin can not be merely transmitted by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunohistochemistry and in situ hybridization analyses revealed a marked reduction in the expression of the IGF 1 receptor , as well as in the GH receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In cell culture , IGF 1 did not stimulate , GH RH slightly stimulated , while MZ 5 156 and JV 1 36 inhibited proliferation of MDA MB 468 cells known to possess defective insulin and IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Functional analysis of these mutants by transfection experiments in a cell line overexpressing the IGF 1 receptor ( NWTb 3 ) found that an inability to bind PSF significantly increased the IGFRE transcriptional activity , while retaining responsiveness to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , when 5T33MMvt cells were injected in vivo ( 5T33MMvt 10 ) , after 18 h the MM cells harvested from BM were IGF 1 receptor and CD44v6 positive . ^^^ In vitro culture of the 5T33MMvt 10 cells could completely down regulate IGF 1 receptor and CD44v6 . ^^^ In fact , we could show that direct contact of 5T33MMvt cells with BM endothelial cells is a prerequisite for IGF 1 receptor and CD44v6 up regulation . ^^^ These data indicate that the BM microenvironment is capable of up regulating molecules such as IGF 1 receptor and CD44v6 , which facilitate homing of MM cells to the BM and support their adhesion to BM stroma . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The role of estrogen receptors and IGF 1 receptors in the synaptic changes has been studied by assessing the number of axo somatic synapses in ovariectomized rats treated with intracerebroventricular administration of the estrogen receptor antagonist ICI 182 , 780 and the IGF 1 receptor antagonist JBI to ovariectomized rats . ^^^ Both the estrogen receptor antagonist and the IGF 1 receptor antagonist blocked the estrogen induced synaptic decrease . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Also , there was a decrease in the level of IGF 1 and IGF 1 receptor mRNA levels by 55 and 35 % , respectively as assessed by semi quantitative RT PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The granulin / epithelin precursor supports tumorigenesis in appropriate cell models and is the only growth factor able to overcome the cell cycle block that occurs in murine fibroblasts after deletion of a functional IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , we hypothesized that part of the proliferative responses to LDLs may be explained by its modulation of IGF 1 or IGF 1 receptor ( IGF 1R ) expression . ^^^ Treatment of rat vascular smooth muscle cells with increasing doses of native LDL dose dependently increased IGF 1 mRNA by up to 2 . 6 fold ; however , native LDL had no effect on IGF 1R mRNA expression . ^^^ In contrast , the same doses of oxidized LDL significantly reduced IGF 1 and IGF 1R mRNA by 80 and 61 % , respectively , and reduced IGF 1 and IGF 1R protein expression by 63 and 46 % . ^^^ In summary , these results suggest that native and oxidized LDLs have differential effects on IGF 1 and IGF 1R expression . ^^^ Because IGF 1 is a potent survival factor for vascular smooth muscle cells , our findings suggest that moderately oxidized LDL may favor proliferation of smooth muscle cells , whereas oxidized LDL may contribute to plaque apoptosis by local depletion of IGF 1 and IGF 1R . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we compared the insulin and IGF 1 receptor binding properties and metabolic and mitogenic potencies of insulin aspart ( B28Asp human insulin ) , insulin lispro ( B28Lys , B29Pro human insulin ) , insulin glargine ( A21Gly , B31Arg , B32Arg human insulin ) , insulin detemir ( NN 304 ) [ B29Lys ( epsilon tetradecanoyl ) , desB 30 human insulin ] , and reference insulin analogs . ^^^ Mitogenic potencies in general correlated better with IGF 1 receptor affinities than with insulin receptor off rates . ^^^ The 2 rapid acting insulin analogs aspart and lispro resembled human insulin on all parameters , except for a slightly elevated IGF 1 receptor affinity of lispro . ^^^ The combination of the B31B32diArg and A21Gly substitutions provided insulin glargine with a 6 to 8 fold increased IGF 1 receptor affinity and mitogenic potency compared with human insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGFBP 3 was originally defined by the somatomedin hypothesis as the principal carrier of IGF 1 in the circulation and the primary regulator of the amount of free IGF 1 available to interact with the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recent evidence points to an obligatory role for the IGF 1 receptor in the establishment and maintenance of the transformed phenotype and reveals that IGF 1 in concert with insulin like binding protein 3 and p 53 is involved in autocrine / paracrine growth signaling pathways as adaptive responses to environmental stimuli . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The addition of the anti receptor antibody to IGF 1 receptor or insulin receptor partially suppressed erythroid colony formation supported with insulin or IGF 1 in both CD34+ / Kit+ cells and LDBMCs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
SHEP cells undergo apoptosis which is prevented by IGF 1 addition or overexpression of the IGF IR ( SHEP / IGF IR cells ) . ^^^ IGF 1 receptor activation and BCL 2 overexpression prevent early apoptotic events in human neuroblastoma . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The invasive activity of IGF IR overexpressing keloid fibroblasts was greatly increased in the presence of IGF 1 , and inhibited by a neutralizing antibody to IGF 1 . ^^^ Insulin like growth factor 1 ( IGF 1 ) / IGF 1 receptor axis and increased invasion activity of fibroblasts in keloid . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Biological relevance was demonstrated in that plasma cell lines with up regulated IGF IR expression levels exhibited mitogenic responses to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This prompted us to explore IGF 1 expression at the protein and mRNA levels and IGF 1 receptor ( IGF 1rec ) immunoreactivity in normal and neoplastic thyroids ( 50 adenomas and 53 carcinomas ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
TAM treatment was correlated to a slight to moderate inhibition of IGF 1 binding to IGF 1R . ^^^ Whereas TAM did not have any strong effect on IGF 1 binding and the expression of IGF 1R at the cell surface , it was was found to efficently block tyrosine phosphorylation of IGF 1R beta subunit . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The proliferative and anti apoptotic actions of IGF are mediated by the IGF 1 receptor ( IGF IR ) , to which both IGF 1 and IGF 2 bind with high affinity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The granulosa cells closest to the oocyte produce abundant insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor is highly expressed by oocytes , suggesting that granulosa derived IGF 1 may have trophic effects on oocyte growth and development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The response to GH could not be abolished by the IGF 1 receptor blocker IGF 1 analogue indicating an IGF 1 independent action of GH . ^^^ The upregulation of PLCbeta 3 by IGF 1 was abolished by preincubation of cardiomyocytes with the IGF 1 receptor antagonist IGF 1 analogue , the tyrosine kinase inhibitor genistein , the extracellular signal related kinase ( ERK ) inhibitor PD 98059 , the phosphatidylinositol 3 ( PI 3 ) kinase inhibitor wortmannin and the p 70 S6 kinase inhibitor rapamycin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , the PI3K / Akt / FKHRL1 pathway is essential for inhibition of apoptosis in response to Epo and SCF , while the IGF 1 receptor utilizes a different pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using this culture system of OPM 6 , we demonstrated that the treatment with DEX plus a monoclonal antibody to the human IGF 1 receptor ( alphaIGF 1R ) leads to the down regulation of the gene expression of Bcl xL , an antiapoptotic gene , and the activation of CPP 32 during this apoptotic process . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 2 is a commonly expressed growth factor in many tumors and may enhance tumor growth , acting via the overexpressed IGF 1 receptor , a cell surface tyrosine kinase receptor . ^^^ The IGF 1 receptor may be overexpressed due to mutations in tumor suppression gene products such as p 53 and WT 1 or growth factors such as bFGF and PDGF . ^^^ Thus , this family of growth factors , especially the IGF 1 receptor , may present an excellent target for new therapeutic agents in the treatment of cancer and other disorders of excessive cellular proliferation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MATERIALS AND METHODS : We have investigated the effect of SA on prostate cancer cell ( DU 145 , LNCaP and PC 3 ) growth and expression of IGFs ( IGF 1 , IGF 2 and IGF 1 receptor ( IGF IR ) ) , IGFBP 3 and vascular endothelial growth factor ( VEGF ) . ^^^ Gene expression studies by RT PCR have demonstrated a decrease in mRNAs of IGF 2 in DU 145 , IGF 1 , and IGF IR in LNCaP , and IGF 2 and VEGF in PC 3 cells and an increase in IGFBP 3 in both DU 145 and PC 3 cells by treatment with SA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : In order to evaluate the role of IGF 1 mediated activation of components of the tissue RAS , we examined the effect of IGF 1 receptor stimulation on cell proliferation , and production of angiotensinogen in cultured VSMC . ^^^ Moreover , angiotensinogen released by the cells to the culture medium was determined by radioimmunoassay with or without the anti IGF 1 receptor antibody alphaIR 3 or captopril . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Elevated levels of IGF IR are observed in a variety of human tumour types , whereas epidemiological studies implicate the IGF 1 axis as a predisposing factor in the pathogenesis of human breast and prostate cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MATERIALS AND METHODS : This study searched for the mRNA expression patterns of components of the IGF system : IGF 1 and IGF 2 , IGF receptors 1 and 2 ( IGF 1R , IGF 2R ) , IGF binding proteins 1 6 ( IGFBP 1 6 ) ) in the most frequent human gastroenteropancreatic neuroendocrine tumours ( gastrinomas , insulinomas , tumours associated with carcinoid syndrome and functionally inactive tumours ) employing reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ In addition , 12 pairs of significantly coexpressed IGF system components were detected ( IGF 1 < > IGF 1R , IGF 1 < > IGF 2R , IGF 1 < > IGFBP 3 , IGF 1 < > IGFBP 6 , IGFBP 3 < > IGF 1R , IGFBP 6 < > IGF 1R , IGFBP 1 < > IGF 2R , IGFBP 3 < > IGF 2R , IGFBP 5 < > IGF 2R , IGFBP 3 < > IGFBP 5 , IGFBP 3 < > IGFBP 6 , IGFBP 5 < > IGFBP 6 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Diethylstilbestrol , 4 hydroxytamoxifen , the raloxifene analog LY 353381 , 2 , 2 bis ( p hydroxyphenyl ) 1 , 1 , 1 trichloroethane ( HPTE ) , bisphenol A , and genistein were shown to mimic E 2 in the uterus by increasing the level of IGF 1 messenger RNA , inducing IGF 1 receptor ( IGF IR ) tyrosine phosphorylation , stimulating the formation of IGF IR signaling complexes , and increasing both proliferating cell nuclear antigen expression and the number of mitotic cells in the epithelium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To gain insight into the mechanisms involved in the cross talk between IGF 1 receptor ( IGF 1R ) and estrogen receptor signaling pathways , we used MCF 7 derived cells ( SX 13 ) , which exhibit a 50 % reduction in IGF 1R expression . ^^^ Taken together , these data suggest that in MCF 7 cells , estrogen potentiates the IGF 1 effect on IGF 1R signaling as well as on the cell cycle components . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor was functionally active . ^^^ Because our data also demonstrate that a significant proportion of neuroendocrine tumors express the IGF 1 receptor and its ligand , interference with this pathway could be useful in the treatment of hypersecretion syndromes and growth of human neuroendocrine tumors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We also utilized three IGF 1 analogs ( [ LongR 3 ] , [ Ala 31 ] , and [ Leu 24 ] [ Ala 31 ] ) with altered affinities for the IGF 1 receptor and / or IGF 1 binding proteins in order to address the mechanism ( s ) of IGF 1 neuroprotection . ^^^ Since all three IGF 1 analogs inhibit cell death to some degree , we interpret these results to mean that IGF 1 mediated inhibition of cell death does not depend upon strong affinities for the IGF 1 receptor or IGF 1 binding proteins . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to detect probable differences in the occurrence and distribution of components of the IGF system , tissue samples from liver , lung , skin , parotid and thyroid gland , gut and cerebellum from SID children ( n=9 ) and controls ( n=6 ) aged between 14 and 258 days of life ( mean 105 days ) were stained immunohistochemically using antibodies against IGF 1 , IGF 2 and their specific IGF 1 receptor ( IGF IR ) . ^^^ In contrast to controls in hepatocytes of SID children a reduction or an absence of immunoreactivity for IGF 1 and IGF IR and a weaker staining for IGF 2 was detected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Accordingly , E ( 2 ) decreased IGF 1R and IGF 1 mRNA in RASMC by 47 % and 33 % . ^^^ Western blot analysis and radioligand binding studies showed that E ( 2 ) also dose dependently decreased IGF 1R protein expression in RASMC by 40 % and 30 % , respectively , and that IGF 1 protein was reduced by 43 % . ^^^ Thus , E ( 2 ) down regulates IGF 1R and IGF 1 expression in vascular smooth muscle cells . ^^^ Estradiol decreases IGF 1 and IGF 1 receptor expression in rat aortic smooth muscle cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we assessed the potential role of insulin like growth factor 1 ( IGF 1 ) , the IGF 1 receptor ( IGF IR ) and IGF binding protein 2 ( IGFBP 2 ) in human colorectal cancer . ^^^ Initial studies demonstrating increased IGF 1 binding and IGF IR density in human colon cancer tissue revealed that a component of iodinated ( 3 [ 125 1 ] iodotyrosyl ) IGF 1 ( 125I ICGF 1 ) binding was not attributable to IGF IR . ^^^ The discrepancy between increased IGF 1 binding , IGF IR density , IGFBP 2 mRNA and the minimal modulation of the IGF IR mRNA implies post transcriptional regulation of IGF IRs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This may be mediated via the IGF 1 receptor , by cross reactivity with the insulin receptor , or by activation of hybrid receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Human retinal endothelial cell ( HREC ) cultures of diabetic and non diabetic origin were examined for the production of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor and IGF binding proteins ( IGFBPs ) using colloidal gold quantitative immunocytochemistry and quantitative reverse transcriptase polymerase chain reaction ( QRT PCR ) . ^^^ The levels of immunoreactivity for IGF 1 receptor and for four IGFBPs ( IGFBP 1 , 2 , 3 and 5 ) were significantly increased in diabetic HREC cultures . ^^^ However , the protein levels for IGF 1 receptor and IGFBP 3 and 4 did not correlate with mRNA levels . ^^^ There were no differences in mRNA levels for IGF 1 receptor and IGFBP 3 and 4 between diabetic and non diabetic HREC cultures , suggesting a post transcriptional regulation of IGF 1 receptor and the two IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The relationships between the insulin like growth factor I / insulin like growth factor binding protein ( IGF I / IGFBP ) system and the IGF 1 receptor characteristics on erythrocytes and PBMCs in healthy subjects in the fasting state were studied to establish whether this would be a valid way of examining IGF 1 receptors in vivo . ^^^ The K ( d ) of the IGF 1 receptor on erythrocytes was positively related to circulating `` free ' ' IGF 1 levels . ^^^ For the IGF 1 receptor on PBMCs no relationship was observed with `` free ' ' IGF 1 levels . ^^^ IGFBP 3 levels were inversely related to the number of IGF 1 binding sites on erythrocytes and to the K ( d ) of the IGF 1 receptor on PBMCs . ^^^ Total IGF 1 , insulin and IGFBP 1 levels showed no relation to the IGF 1 receptor on erythrocytes and PBMCs in the fasting state . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of GH receptor , IGF 1 receptor and IGF 1 mRNA in the kidney and liver of rats recovering from unilateral renal ischemia . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transcription of the IGF 1 receptor gene is controlled by a number of tumor suppressors , including WT 1 , p 53 , and BRCA 1 . ^^^ The insulin like growth factor 1 receptor ( IGF 1 R ) has a central role in normal cellular proliferation as well as in transformation processes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor phosphorylation was evaluated with Western analysis . ^^^ IGF 1 receptor phosphotyrosine was diminished in chondrocytes exposed to NO . ^^^
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Low IGF 1 receptor expression was detected in preneoplastic foci and adjacent nonaltered liver tissue . ^^^ However , HCC tissue consistently showed an increased IGF 1 receptor expression , rendering these tissues susceptible to the mitogenic effects of IGF . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since the actions of IGF 1 in target tissues are mediated by the type 1 IGF receptor , the concentrations of IGF 1 receptor mRNA and protein were examined in pig corpora lutea at different stages of the oestrous cycle . ^^^ Northern and slot blots were used to examine mRNA , and western blots were used to measure the concentrations of IGF 1 receptor protein in the pig corpus luteum . ^^^ On northern blots , luteal IGF 1 receptor mRNA was present as a single 11 kb transcript . ^^^ The slot blots showed that the steady state expression of IGF 1 receptor mRNA increased significantly ( P < 0 . 05 ) from its lowest value on day 4 , to reach a maximum on days 13 16 . ^^^ IGF 1 receptor mRNA was also expressed to a greater extent in large compared with small luteal cells ( P < 0 . 05 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transduction of cardiomyocytes with constitutively active PI 3 kinase specifically lead to serine phosphorylation of Akt , whereas phosphorylation of IGF 1 receptor , IRS1 / 2 and p44 / 42 mitogen activated protein kinase were not increased . ^^^ These findings indicate the existence of an IGF 1 receptor PI 3 kinase caspase 3 pathway in cardiomyocytes that plays an important role in the anti apoptotic actions of IGF 1 in heart . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Treatment of C 6 cells with 200 microg / ml Poly ( IC ) for 24 h reduced IGF 1 receptor mRNA levels to 50 % of the control level . ^^^ Treatment of confluent C 6 cells with 200 microg / ml Poly ( IC ) for 24 h decreased levels of immunoreactive IGF 1 in conditioned medium ( CM ) to 55 % of the control value , decreased IGF 1 receptor beta subunit levels to 28 % of the control value , and decreased levels of IGFBP 3 , IGFBP 4 , and IGFBP 5 protein in CM to 45 % , 50 % , and 30 % of the control values , respectively . ^^^ These results suggest that IGF 1 gene expression is down regulated by Poly ( IC ) treatment and that IGF 1 bioavailability and action in C 6 cells are also altered due to decreases in IGF 1 receptor and binding protein levels . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Functional inactivation of the IGF 1 receptor delays differentiation of skeletal muscle cells . ^^^ However , the potential role of the tyrosine kinase IGF 1 receptor ( thought to be the principal mediator of both IGF 1 and 2 signaling in skeletal muscle ) in the decision of myoblasts to begin differentiation following serum withdrawal is unknown . ^^^ To explore the role of the IGF 1 receptor in this decision by skeletal myoblasts , we functionally inactivated endogenous IGF 1 receptors in mouse C2C12 cells using a dominant negative , kinase inactive IGF 1 receptor in which the ATP binding site lysine ( K ) at residue 1003 has been mutated to alanine ( A ) . ^^^ Cell lines with the greatest degree of mutant IGF 1 receptor expression ( A / K cells ) demonstrated functional inactivation of endogenous IGF 1 receptors as determined by their impaired ability to phosphorylate the principal substrate of the IGF 1 receptor , IRS 1 , in response to treatment with IGF 1 . ^^^ Thus , the IGF 1 receptor regulates the timing of myoblast differentiation induced by serum withdrawal . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MV displaying EGF or IGF 1 efficiently entered CD 46 negative rodent cells expressing the human EGF or the IGF 1 receptor , respectively , and the EGF virus caused extensive syncytium formation and cell death . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The frequent overexpression of insulin like growth factor 1 receptor ( IGF 1 R ) in rectal adenocarcinoma suggests that inhibition of the signal transduction pathway may be a novel approach to enhance tumor response . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that the response evoked by the IGF 1 receptor could act as a binary molecular switch controlling GH mRNA expression in somatotrophs . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
JB 3 , an IGF 1 receptor antagonist , inhibits early renal growth in diabetic and uninephrectomized rats . ^^^ In the present study , an IGF 1 receptor antagonist ( JB 3 ) was synthesized , and its effect on the renal growth that follows the induction of diabetes or unilateral nephrectomy ( UNx ) was examined . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , the presence of mRNAs of IGF 2 and of receptors for IGF 1 ( IGF IR ) , growth hormone ( GHR ) and insulin ( IR ) , as well as mRNAs of IGF binding proteins ( IGFBP 1 , 2 and 3 ) were assessed by RT PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Octreotide significantly suppressed IGF 1 induced HA secretion by the patient ' s fibroblasts , but not by normal fibroblasts , which suggests that expression of IGF 1 receptor on fibroblasts , or its affinity for IGF 1 , are upregulated in PTM , resulting in the oversecretion of HA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In a yeast two hybrid screen of a human fetal brain library , we have previously identified SOCS 2 as a binding partner of the activated IGF 1 receptor ( IGFIR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These cells underwent apoptotic death in low serum differentiation medium but could be maintained as viable myoblasts by IGF analogues that activated the IGF 1 receptor or by unrelated growth factors such as platelet derived growth factor BB ( PDGF BB ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This responsiveness to IGF 1 was conditioned by a differential expression of the IGF system components ( IGFBPs and IGF 1 receptor ) and particularly of the IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Comparison of the biological activities of native and the disulfide bond isomer of human IGF 1 highlight the importance of Tyr 24 , Phe 25 , Phe 49 Cys52 and Phe 16 in binding to the IGF 1 receptor or specific IGFBPs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of IGFBP 3 and the fragments on IGF 1 receptor ( IGFIR ) signaling pathways was studied by testing IGF 1 induced receptor autophosphorylation in IGFIR overexpressing NIH 3T3 cells . ^^^ The ( 1 97 ) NH 2 terminal fragment inhibited IGFIR autophosphorylation at high concentrations , and this effect seems largely attributable to sequestration of IGF 1 . ^^^ In contrast , no inhibition of IGF 1 induced IGFIR autophosphorylation was detectable with the ( 98 264 ) and ( 184 264 ) COOH terminal fragments , despite their ability to bind IGF . ^^^ Differential effects of insulin like growth factor ( IGF ) binding protein 3 and its proteolytic fragments on ligand binding , cell surface association , and IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In other systems , the IGF 1 concentration regulates IGF 1R expression and thus high concentrations lead to down regulation of the receptor . ^^^ High insulin like growth factor 1 ( IGF 1 ) and insulin concentrations trigger apoptosis in the mouse blastocyst via down regulation of the IGF 1 receptor . ^^^ Here , data show a decrease in IGF 1 receptor protein expression , both by confocal immunofluorescent microscopy and by Western analysis upon exposure to 130 nM IGF 1 . ^^^ Insulin stimulated glucose uptake , an event regulated via the IGF 1 receptor , is decreased upon exposure to excess IGF 1 , suggesting decreased function of the receptor . ^^^ The data also show that , by blocking receptor signal transduction or by decreasing receptor expression , the apoptotic event can be recreated , thus strongly suggesting that the mechanism of high IGF 1 induced apoptosis is decreased downstream IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF II / IGF 1 receptor pathway up regulates COX 2 mRNA expression and PGE 2 synthesis in Caco 2 human colon carcinoma cells . ^^^ In the present study , we demonstrate that COX 2 expression and PGE 2 synthesis are up regulated by an IGF II / IGF 1 receptor autocrine pathway in Caco 2 colon carcinoma cells . ^^^ Up regulation of COX 2 expression by IGF 2 is mediated through activation of IGF 1 receptor because : ( 1 ) treatment of Caco 2 cells with a blocking antibody to the IGF 1 receptor inhibits COX 2 mRNA expression ; ( 2 ) transfection of Caco 2 cells with a dominant negative IGF 1 receptor reduces COX 2 expression and activity . ^^^ Also , the blockade of the PI 3 kinase , that mediates the proliferative effect of IGF 1 receptor in Caco 2 cells , inhibits IGF 2 dependent COX 2 up regulation and PGE 2 synthesis . ^^^ Moreover , COX 2 expression and activity inversely correlate with the increase of apoptosis in parental , IGF 2 and dominant negative IGF 1 receptor transfected cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Viability could be sustained and differentiation enabled by IGF analogues that activated the IGF 1 receptor ; survival was dependent on stimulation of phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and its receptor play a pivotal role in many cancers , and therefore , IGF 1R is an attractive target for the design of inhibitors . ^^^ Substrate competitive inhibitors of IGF 1 receptor kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover the role of the IGF 1 receptor ( IGF IR ) in this process was evaluated . ^^^ Stimulation with IGF 1 or Ang 2 ( 10 ( 7 ) M ) increased IGF IR expression 5 . 7+ / 0 . 5 fold and 3 . 6+ / 0 . 5 fold respectively . ^^^ The IGF 1 induced overexpression of the IGF IR was reduced by ACE inhibition with moexiprilat ( 10 ( 7 ) M ) by 79+ / 7 % and by AT ( 1 ) receptor blockade with CV 11974 ( 10 ( 7 ) M ) by 79+ / 5 % . ^^^ These data demonstrate that the mitogenic action of IGF 1 in neonatal rat cardiac fibroblasts is in part mediated by activation of the renin angiotensin system ( RAS ) with subsequent upregulation of IGF IR expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition we demonstrated that the marrow microenvironment can upregulate the expression of the IGF 1 receptor on 5T mouse myeloma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 promotes the survival of multiple cell types by activating the IGF 1 receptor ( IGF IR ) , which signals downstream to a serine / threonine kinase termed Akt . ^^^ Hence , in the retina of diabetic rats , as in the retina of diabetic human donors , IGF 1 mRNA levels are substantially lower than in age matched nondiabetic controls , whereas IGF IR activation and signaling are not affected , at least for some time . ^^^ This finding suggests that in the diabetic retina , the activation of the IGF IR is modulated by influences that compensate for , or are compensated by , decreased IGF 1 synthesis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , our study suggests that concomitant overexpression of multiple signaling components of the IGF IR pathway leads to the amplification of IGF 1 mediated MAP kinase signaling and resultant sensitization to PD 098059 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of IGFs are mediated through the IGF 1 receptor , which is also involved in cell transformation induced by tumor virus proteins and oncogene products . ^^^
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We conclude that the IGF 1 receptor tyrosine kinase is not a dual specificity kinase and that autophosphorylation of the beta subunit is by a trans mechanism . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Human GRB 10 on chromosome 7 , a homologue of the mouse imprinted gene Grb 10 , is a candidate , because GRB 10 has a suppressive effect on growth , through its interaction with either the IGF 1 receptor or the GH receptor , and two patients with RSS were shown to have a maternally derived duplication of 7p11 p 13 , encompassing GRB 10 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In human SH SY5Y neuroblastoma cells , ethanol inhibited tyrosine autophosphorylation of the IGF 1 receptor . ^^^ The data indicate that the IGF 1 receptor is a target for ethanol in SH SY5Y cells However , there is diversity in the sensitivity of signaling elements within the IGF 1 receptor tyrosine kinase signaling cascades to ethanol , which can be related to the inhibition of specific functional events in neuronal activation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The growth effects of these genes are exerted primarily through IGF 1 receptor ( IGF IR ) . ^^^ We have now studied the modulation of IGF 1 , IGF 2 and IGF IR in hypoxia and the ability of picroliv to modify their expression in vivo . ^^^ Male Sprague Dawley rats , placed in 10 % oxygen for 4 days , were sacrificed , and the expression of IGF 1 , IGF 2 and IGF IR was determined by immunohistochemistry , in situ hybridization and reverse transcriptase polymerase chain reaction ( RT PCR ) in brain , liver and lung . ^^^ IGF 1 and IGF IR were expressed in distinct regions of the brain but not in liver or lung . ^^^ IGF 1 was mainly expressed in the hippocampus and cerebellum , whereas IGF IR expression was also observed in the cortex . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To elucidate this possibility , we investigated the cellular localization and hormonal regulation of mRNAs for IGF 1 and 2 , their cognate receptors ( IGF1R , IGF2R ) , and IGF binding proteins 2 5 ( BPs 2 5 ) in the rhesus monkey mammary gland . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PD 98059 inhibited activation of Erk and LY 294002 repressed activation of Akt in response to IGF 1 , but did not affect tyrosine phosphorylation of the IGF IR , IRS 1 , IRS 2 , or Shc . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MATERIAL AND METHODS : We examined binding characteristics and concentrations of both IGF receptors in normal adult human adrenocortical glands , and compared them with the IGF 1 receptor binding in adrenocortical rumours of various origins . ^^^ The human IGF 1 receptor was overexpressed in the mouse adrenocortical tumour cell line Y 1 , and growth studied in response to IGF stimulation . ^^^ RESULTS : While the abundance of the IGF 1 receptor in adrenocortical hyperplasias and adenomas was similar to normal tissue , a strong overexpression of the intact IGF 1 receptor was found in three out of four adrenocortical carcinomas . ^^^ Y 1 cells overexpressing the human IGF 1 receptor respond to IGF 1 with an increase in thymidine incorporation by 140 % . ^^^ High local levels of IGF 2 in combination with elevated IGF 1 receptor concentrations would represent a significant growth advantage of the adrenocortical carcinoma cell and could contribute to a highly malignant phenotype . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and IGF 1 receptor mRNAs were concentrated in cortical neurons in a distribution similar to Gluts 3 and 4 . ^^^ IGF 1 mRNA levels were significantly increased in E 2 treated animals but IGF 1 receptor mRNA levels were not altered by hormone treatment . ^^^ Tamoxifen increased cerebral cortical Glut 3 and 4 mRNA levels , but did not affect Glut 1 , IGF 1 , or IGF 1 receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Minireview : tissue specific versus generalized gene targeting of the igf 1 and igf1r genes and their roles in insulin like growth factor physiology . ^^^
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Expression of alpha ( 1 ) PDX resulted in a proinsulin like growth factor 1 receptor ( pro IGF 1R ) processing blockade , hence inhibiting the ability of exogenous IGF 1 to induce tyrosine phosphorylation of its beta subunit and insulin related substrate 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor binds to its ligand and activates two intracellular processes mainly a Shc mediated pro mitotic pathway and an anti apoptotic pathway mediated by IRS and Akt . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Poorly invasive M 27 carcinoma cells expressing low receptor numbers were transfected with a plasmid vector expressing IGF 1 receptor cDNA in which single or multiple tyrosine codons in the kinase domain , namely Tyr 1131 , Tyr 1135 , and Tyr 1136 or the C terminal tyrosines 1250 and 1251 were substituted with phenylalanine . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we report on the isolation of a PDZ domain protein , here designated as IIP 1 , insulin like growth factor 1 ( IGF 1 ) receptor interacting protein 1 , which binds to the IGF 1 receptor , but not to the related insulin receptor , and which is involved in the regulation of cell motility . ^^^ The interaction between the IGF 1 receptor and IIP 1 as well as a splice variant IIP 1 / p26 was demonstrated in the yeast two hybrid system . ^^^ Analysis of deletion mutants indicates that the PDZ domain of IIP 1 mediates interaction with the C terminal tail of the IGF 1 receptor ( serine threonine cysteine ) . ^^^ This finding demonstrates that the C terminus of the IGF 1 receptor acts as novel PDZ domain binding site . ^^^ Immunofluorescence analysis revealed an overlapping localization of IIP 1 and the IGF 1 receptor in the breast cancer cell line MCF 7 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed : The mRNAs of IGF 1 , IGF 2 and IGF 1R were strongly expressed in serum free cultured T 24 cell line , whereas normal urothelial cells did not express these factors / receptors or only in trace levels ; T 24 cell responded far better to growth stimulation by IGF 1 than did normal urothelial cells ; blockage of IGF1R by antisense oligodeoxynucleotide ( ODN ) significantly inhibited the growth of T 24 cell and enhanced sensitivity and apoptosis of T 24 cells to mitomycin ( MMC ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We also found coinduction of several groups of related genes that might represent functional modules within the ischemic neuronal transcriptome , including VEGF and its receptor , NRP 1 ; the IGF 1 receptor and the IGF 1 binding protein IGFBP 2 ; Rb , the Rb binding protein E2F1 , and the E2F related transcription factor , TFDP 1 ; the CACNB 3 and CACNB 4 beta subunits of the voltage gated calcium channel ; and caspase 3 and its substrates , ACINUS , FEM 1 , and GSN . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast to the elevated IGF 1R expression in ScN2a , receptor binding studies revealed an 80 % decrease in specific ( 125 ) 1 IGF 1 binding sites compared with N2a cells . ^^^ Furthermore , ScN2a showed no significant difference in IGF 1 induced proliferative response , despite the noticeable elevated IGF 1R expression , putatively explained by the reduced IGF 1R binding affinity . ^^^
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Expression in 32D IGF IR cells of a dominant negative mutant of Stat 3 ( DNStat 3 ) inhibits IGF 1 mediated differentiation . ^^^ This increase , however , is IGF 1 dependent and is abrogated by a mutation at tyrosine 950 of the IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Initial analysis for mRNA expression demonstrated the following : GH receptor ( 5 / 5 cell lines positive ) , IGF 1 ( 0 / 5 ) , IGF 2 ( 0 / 5 ) , IGF 1 receptor ( 5 / 5 ) , IGF 2 receptor ( 2 / 5 ) . ^^^
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METHODS : We studied the mRNA expression of IGF 1 , IGF 1 receptor , and IGF binding proteins ( BP ) using sensitive RNase protection assays following subcutaneous implantation of growth hormone pituitary cells ( GH ( 3 ) ) in rats . ^^^
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To elucidate a role for the IGF IR in the pathogenesis of PV , basal and IGF 1 stimulated tyrosine phosphorylation of the IGF IR beta subunit in PBMNC of PV patients or controls was determined by WLB . ^^^ However , no differences in tyrosine phosphorylation of the IGF IR in PV patients , neither basal nor IGF 1 induced , were detected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Antisense IGF 1 receptor mRNA induces an antitumour response , resulting in complete brain tumour regression . ^^^ Clinical trials for the treatment of brain tumours in humans based on a gene transfer protocol using IGF 1 receptor antisense are under way . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Estrogen can increase insulin like growth factor 1 receptor ( IGF IR ) and insulin receptor substrate 1 ( IRS 1 ) expression , two key components of IGF 1 mediated signaling . ^^^ However , ERalpha positive C 4 12 cells now exhibited estrogen induction of IGF IR and IRS 1 levels and responded mitogenically to both estrogen and IGF 1 . ^^^
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Western blotting analyses proved the existence of insulin like growth factor in the protein purified from rabbit seminal plasma and immunofluorescence staining showed the existence of IGF 1 receptor in rabbit spermatozoa . ^^^
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High doses of ICI increased mammary IGF 1 gene expression by 2 fold ( P < 0 . 01 ) but decreased IGF 1R and its autophosphorylation to approximately 30 % of the control mammary gland . ^^^
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The lowest level of IGF 1R detected after 15 min of activation suggested that the effects of IGF 1 occur at the initiation of cell activation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 2 ( IGF 2 ) plays a key role in mitogenesis during development and tumorigenesis and is believed to exert its mitogenic functions mainly through the IGF 1 receptor . ^^^ Here we investigated the mitogenic signaling of IGF 2 via the Akt / Glycogen synthase kinase 3 ( Gsk 3 ) axis employing R IR ( A ) cells that are IGF 1 receptor null mouse embryonic fibroblasts expressing the human IR ( A ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In vivo progression of LAPC 9 and LNCaP prostate cancer models to androgen independence is associated with increased expression of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Anchorage independent growth of fibroblasts that express a truncated IGF 1 receptor . ^^^ These results provide evidence that an IGF 1 receptor consisting of only the transmembrane and cytoplasmic domain of the beta subunit can signal pathways leading to anchorage independent growth . . ^^^ The purpose of this investigation was to study signaling by an insulin like growth factor 1 receptor ( IGF 1 R ) that lacks the extracellular portion of the receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We speculate that the IGF 1 activated IGF 1 receptor , in response to E 2 , directly or indirectly modifies insulin receptor substrate 2 , probably through phosphorylation , leading to ubiquitination and subsequent degradation of this docking protein by the proteasome . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
ZO 1 expression ( mRNA and protein ) was induced by IGF 1 and was blocked in MCF 7 cells with a tyrosine kinase defective IGF IR mutant . ^^^
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Rats were killed 48 h after declamping , and the following studies were performed : in serum , creatinine and urea nitrogen ; and in kidneys , histologic damage score , cellular proliferation by bromodeoxyuridine labeling , apoptosis by morphologic criteria , macrophage infiltration by immunohistochemistry using a specific antibody against ED 1 , neutrophil infiltration by naphthol AS D chloroacetate esterase staining , and levels of IGF 1 and IGF 1 receptor mRNA by RNase protection assay . ^^^
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In this study we investigated changes in the spinal cord insulin like growth factor 1 peptide ( IGF 1 ) and its receptors ( IGF IR ) after hind limb immobilization for 5 days , 2 , 4 , and 8 weeks . ^^^ IGF 1 levels were measured by radioimmunoassay ( RIA ) whereas IGF IR and nAChRs were measured by quantitative receptor autoradiography . ^^^ Spinal cord IGF 1 levels decreased significantly after 5 days , 2 and 4 weeks of immobilization , whereas IGF IR increased significantly after 4 and 8 weeks compared to controls . ^^^ Our findings suggest that the early decrease in the IGF 1 level and the late upregulation in the IGF IR in the spinal cord might represent a nervous system response to disuse . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
H 19 7 / IGF IR cells are rat hippocampal cells expressing a human IGF 1 receptor , which differentiate to a neuronal phenotype when stimulated by IGF 1 at 39 degrees C . ^^^ IGF 1 induces serine phosphorylation and down regulation of the endogenous IRS 1 upon differentiation of H 19 7 / IGF IR cells . ^^^ Over expression of wild type IRS 1 in H 19 7 / IGF IR cells abolishes IGF 1 induced differentiation at 39 degrees C . ^^^ The role of Akt in the inhibition of the differentiation program was confirmed by using the inhibitor of Class 1 PI 3 kinases LY 29400 , which restores IGF 1 induced differentiation of H 19 7 / IGF IR / IRS 1 cells . ^^^ These experiments confirm the importance of MAPK in the mechanism of IGF 1 mediated differentiation of H 19 7 / IGF IR cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : Insulin like growth factors ( IGF 1 and IGF 2 ) , the IGF 1 receptor ( IGF 1R ) , and IGF binding proteins ( IGFBPs ) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors . ^^^ METHODS : To evaluate the role of the IGF system in lymphangioleiomyomatosis ( LAM ) , we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF 1 , IGF 2 , IGF 1R , and IGFBP 2 , 4 , 5 , and 6 in lung tissue from 18 LAM patients . ^^^ RESULTS : IGF 1 , ICGF 2 , IGF 1R , IGFBP 1 , IGFBP 2 , IGFBP 4 , IGFBP 5 , and IGFBP 6 were expressed by LAM cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The growth promoting activities of [ A5Glu ] human insulin and [ A8Tyr ] human insulin were increased 6 fold and 2 fold , respectively , compared with native insulin , indicating that their growth promoting activities might be expressed by , or mainly by , binding to the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To elucidate the molecular action of FSH and IGF 1 , we cloned cDNAs for newt IGF 1 and IGF 1 receptor ( IGF IR ) , and examined their mRNA expression in organ culture during newt spermatogenesis . ^^^ Northern blot and reverse transcription polymerase chain reaction ( RT PCR ) analyses revealed that IGF 1 mRNA was highly expressed in somatic cells ( mostly Sertoli cells ) at the secondary spermatogonial stage but barely in germ cells , and that IGF IR mRNA was expressed in both germ and somatic cells at all stages examined . ^^^ Also , rhIGF 1 increased IGF 1 mRNA expression , whereas IGF IR mRNA expression declined slightly . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Correlative analyses of IGF 1 , p 53 , and Ki 67 ( MIB 1 ) immunohistochemistry and IGF 1 receptor ( IGF 1R ) mRNA expression were performed to examine the cellular pattern of IGF 1 signaling in 39 cases of astrocytoma ( World Health Organization grades 2 4 ) . ^^^ Tumor cells expressing IGF 1 and IGF 1R were present in all tumor grades . ^^^ The proportion of tumor cells that expressed IGF 1 correlated with both histopathologic grade and Ki 67 labeling indices , while expression of IGF 1R mRNA correlated with Ki 67 indices . ^^^ The distinctive correlative patterns of IGF 1 and IGF 1R expression in glioblastomas also suggest that IGF 1 signaling has an association with the development of malignant phenotypes related to aberrant angiogenesis and invasive tumor interactions with reactive brain . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Peripheral blood mononuclear cells were isolated and RNA for GH receptor ( GHR ) , IGF 1 receptor ( IGF IR ) and thyroid hormone receptor ( TRalpha 1 ) was amplified by RT PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
ER negative breast cancer cells often express low levels of the IGF IR and fail to respond to IGF 1 with mitogenesis . ^^^ The extent of IGF 1 induced migration reflected IGF IR levels and required the activation of phosphatidylinositol 3 kinase ( PI 3K ) and p 38 kinases . ^^^ The impaired IGF 1 growth response of ER negative cells was not caused by a low IGF IR expression , defective IGF IR tyrosine phosphorylation , or improper tyrosine phosphorylation of IRS 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factors ( IGFs ) are potent proliferation factors and potently inhibit apoptosis acting via the ubiquitously expressed IGF 1 receptor . ^^^ Within IGF 1 receptor signalling , key to the inhibition of apoptosis are the RAS / RAF / mitogen activated protein ( MAP ) kinase pathway and the PI 3 ' kinase pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Experimental IGF 1 receptor deficiency generates a sexually dimorphic pattern of organ specific growth deficits in mice , affecting fat tissue in particular . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Changes in the relative abundance of mRNA transcripts for insulin like growth factor ( IGF 1 and IGF 2 ) ligands and their receptors ( IGF IR / IGF IIR ) in preimplantation bovine embryos derived from different in vitro systems . ^^^ The aim of this study was to determine the relative abundance of mRNAs for the insulin like growth factor 1 ( IGF 1 ) and IGF 2 ligands , and for the IGF receptors ( IGF IR and IGF IIR ) in in vitro preimplantation bovine embryos from the oocyte to the hatched blastocyst stage using two different culture systems : TCM 199 supplemented with oestrous cow serum , or synthetic oviduct fluid supplemented with polyvinyl alcohol . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report herein that the pure anti oestrogen ICI 182 , 780 ( ICI ) reduces Ki 67 labelling index and IGF 1 receptor levels in rat prostate . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Finally , EtOH did not impair IGF 1 receptor autophosphorylation , but inhibited the ability of insulin to phosphorylate its own receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Extremely high insulin concentrations ( 860 nM ) and 10 nM trIGF 1 , a truncated form of IGF 1 with the same affinity for the IGF 1 receptor as the full length IGF 1 , but with lower activity on the insulin receptor , also upregulated UCP 3 . ^^^ We conclude that SH SY5Y cells express UCP 3 natively and that the expression is regulated by IGF 1 via the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Sciatic nerve mRNA expression of IGF 1 , IGF 1 receptor , NGF , and p 75 ( low affinity NGF receptor ) , as well as protein expression of C FOS , were examined at various time points following crush injury and compared with age and sex matched nondiabetic BB / Wor rats . ^^^ The earliest immediate gene responses were those of IGF 1 and IGF 1 receptor , which peaked at 0 . 5 h post crush in control rats . ^^^ In diabetic rats , IGF 1 peaked at 24 h whereas IGF 1 receptor mRNA revealed no early peak . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Crystal structure of bisphosphorylated IGF 1 receptor kinase : insight into domain movements upon kinase activation . ^^^ RESULTS : We have determined the 2 . 1 A crystal structure of the IGF 1 receptor protein tyrosine kinase domain phosphorylated at two tyrosine residues within the activation loop ( IGF 1RK2P ) and bound to an ATP analog . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated the specific localization of IGF 1 and its receptor ( IGF 1R ) and their association with apoptosis and the expression of apoptosis related proteins in early and advanced atherosclerotic lesions . ^^^ Immunohistochemistry and in situ hybridization revealed significantly higher expression of IGF 1 and IGF 1R in the media than in the intima of early atherosclerotic lesions ( P < 0 . 01 ) . ^^^ In advanced atherosclerotic plaques , the expression of IGF 1 and IGF 1R was significantly lower in the intimal regions with macrophage infiltration than in those without macrophage infiltration or than in the media ( P < 0 . 01 ) . ^^^ Furthermore , IGF 1 and IGF 1R immunoreactivity was markedly lower in intimal TUNEL positive VSMC compared with intimal BAX positive and medial VSMC ( P < 0 . 01 ) . ^^^ We conclude that IGF 1 and IGF 1R expression are reduced in the deep intima of early atherosclerotic lesions and in areas of advanced plaques with macrophage infiltration . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
LDL , in pathophysiological concentrations , affect the IGF 1 signaling pathway at multiple levels : 1 ) they induce phosphorylation of IGF 1 receptor beta and IRS 1 in a time and dose dependent manner ; 2 ) they up regulate IRS 1 associated PI 3 kinase / Akt activation in response to IGF 1 at early times ; and 3 ) they show additive effects with IGF 1 on extracellular signal regulated MAPK 1 / 2 phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mechanism of IGF 1 action on the TEB was studied by determining the requirement for the IGF 1 receptor ( IGF IR ) in IGF 1 dependent ductal development . ^^^ Targeted disruption of the IGF 1 receptor gene decreases cellular proliferation in mammary terminal end buds . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor and the related insulin receptor are similar in structure and activate many of the same postreceptor signaling pathways , yet they mediate distinct biological functions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We measured concentrations of immunoreactive IGF 1 in plasma , jejunum , and colon , IGF 1 receptor binding , and levels of IGF receptor , IGF 1 , IGF binding protein ( IGFBP ) 3 and IGFBP 5 mRNA in residual jejunum and colon 7 days after resection and / or IGF 1 treatment . ^^^ IGF 1 receptor number was increased ( 74 99 % ) in jejunum and colon due to resection ; IGF 1 mRNA was increased 5 fold in jejunum and 15 fold in colon due to resection . ^^^ IGF 1 treatment had no significant effect on IGF 1 mRNA or IGF 1 receptor number . ^^^ Thus resection upregulated IGF 1 receptor number and IGF 1 mRNA in residual jejunum and colon , but differential adaptation of these segments correlated with differential regulation of IGFBP 5 mRNA . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Necrosis of cells of the collecting ducts and loops of Henle could explain the loss of IGF 1 receptor concentration in the medulla . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunohistochemistry showed strong IGF 1 receptor immunoreactivity in the prostatic epithelial cells of untreated animals . ^^^ In treated rats , both IGF 1 receptor protein and IGF 1 mRNA levels decreased significantly , and IGF 1 mRNA was mainly expressed in prostatic stromal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factors ( IGF 1 and 2 ) play an important role in metabolic and mitogenic activities through stimulation of the IGF 1 receptor on the cell surface . ^^^ Whereas IGF 1 peptide variants , which bind to IGFBPs but not the IGF 1 receptor , have been shown to be potent IGF / IGFBP inhibitors , small molecule nonpeptide IGF / IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Studies using an antibody ( alpha IR 3 ) against the IGF 1 receptor , and compounds with low affinity for IGFBPs , such as insulin and des ( 1 3 ) IGF 1 , showed that an interaction between IGF 1 and IGFBP 5 was necessary to detach this IGFBP from its binding sites . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , the unique biological functions of IGF 1 receptor make it a target for therapeutic intervention in human cancer . ^^^ Using its isolated tyrosine kinase domain , we show that the IGF 1 receptor is regulated by intermolecular autophosphorylation at three sites within the kinase activation loop . ^^^ Steady state kinetic analyses of the isolated phosphorylated forms of the IGF 1 receptor kinase ( IGF1RK ) reveal that each autophosphorylation event increases enzyme turnover number and decreases Km for ATP and peptide . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGFs , IGF 1 and IGF 2 , regulate fetal growth by activating IGF type 1 receptors ( IGF IR ) . ^^^ We investigated these IGF IR binding parameters in two additional groups of growth retarded children ( Turner syndrome and patients with chronic renal failure ) , in whom the IGF 1 axis was not believed to be the primary cause , and found that Kd and Bmax were normal or nearly normal . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
While SH SY5Y and SHEP cells use different insulin receptor substrate ( IRS ) isoforms to transduce signals from the IGF 1 receptor , IGF 1 has the same relative effect on the motility of both cell lines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Low TSH requirement and goiter in transgenic mice overexpressing IGF 1 and IGF Ir receptor in the thyroid gland . ^^^ Although the autocrine production of IGF 1 in the thyroid gland suggests an important physiological function for this factor in these processes , the exact role of the IGF I / IGF 1 receptor system in vivo remains unclear . ^^^ To investigate the in vivo function of the IGF I / IGF 1 receptor system , transgenic mice overexpressing human IGF 1 , IGF 1 receptor , or both in the thyroid were generated . ^^^ A decreased TSH level together with a slightly increased serum T ( 4 ) concentration and increased thyroidal iodine uptake were also observed , suggesting that IGF 1 and IGF 1 receptor stimulate thyroid function to some extent in vivo . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It is possible that Shc and insulin receptor substrate ( IRS ) 1 can interact competitively , via their phosphotyrosine binding ( PTB ) domains , with the activated IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) 1 down regulates type 1 IGF receptor ( IGF 1R ) and reduces the IGF 1 response in A 549 non small cell lung cancer and Saos 2 / B 10 osteoblastic osteosarcoma cells . ^^^ The insulin like growth factor type 1 receptor ( IGF 1R ) mediates the acute metabolic effects of IGF 1 as well as IGF 1 stimulated cell proliferation and protection from apoptosis . ^^^ We , therefore , investigated whether intrinsic IGFBPs interfere with IGF 1 induced regulation of IGF 1R expression and with the biological response to IGF 1 in two human tumor cell lines , the non small cell lung cancer cell line A 549 and the osteoblastic osteosarcoma cell line Saos 2 / B 10 . ^^^ We compared the growth rates , IGFBP production , IGF 1 binding characteristics , IGF 1R protein and mRNA levels , and the acute IGF 1 response ( stimulation of glycogen synthesis ) after pretreatment of the cells in serum free medium with or without added IGF 1 or medium supplemented with 5 % fetal calf serum ( FCS ) . ^^^ As compared to FCS , IGF 1 pretreatment in both cell lines decreased the number of specific IGF 1 binding sites , down regulated total and membrane IGF 1R protein , and largely reduced or abolished the acute IGF 1 response without affecting IGF 1R mRNA levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Combining immunofluorescence with in situ ligand binding , we showed that IGF 1 His binding corresponded to the IGF 1 receptor ( IGFR 1 ) distribution in human fetal kidney . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similar experiments performed with other members of the Grb 7 family , Grb 7 and Grb 10 , and with IGF 1 receptor argue in favor of a specific inhibition of the IR catalytic activity by Grb 14 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cardiomyocyte aging is gender dependent : the local IGF 1 IGF 1R system . ^^^ To determine whether insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF 1R ) are implicated in the aging process of the heart , and if their impact differs in the two genders , the expression of IGF 1 , and extracellular alpha subunit and transmembrane beta subunit of IGF 1R was measured in left ventricular myocytes isolated from male and female Fischer 344 rats at 3 , 8 , 12 , 16 , and 26 months after birth . ^^^ In conclusion , the enhanced IGF 1 IGF 1R system in female myocytes may condition the favorable outcome of age in this gender . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study investigates the influence of T ( 3 ) on IGF 1 , IGF 2 , IGF 1 receptor ( IGF 1R ) , and IGF binding protein ( IGFBP ) transcripts , and on IGF 1 action in human osteoblastic cells ( hOB ) under serum free culture conditions . ^^^ We conclude that IGF 1R and IGFBP 5 are thyroid hormone target genes in human osteoblasts , whereas IGF 1 mRNA expression itself appears not to be regulated by T ( 3 ) in hOB . ^^^ However , T ( 3 ) stimulates IGF 1R mRNA expression as well as IGF 1 binding and IGF 1 induced cell proliferation in osteoblasts , thus suggesting thyroid hormone may potentiate the effect of IGF 1 at the receptor level . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor binding protein 3 ( IGFBP 3 ) binds IGF 1 and IGF 2 with high affinity , at least an order of magnitude higher than the affiniy of the IGFs for the IGFIR . ^^^ IGFBP 3 inhibited IGF 1 , IGF 2 , Des ( 1 3 ) IGF 1 and Long ( R 3 ) IGF 1 induced IGFIR phosphorylation in a dose dependent manner at similar concentration range but not QAYL induced IGFIR P . ^^^ The ( ( 1 97 ) ) IGFBP 3 fragment was able to inhibit only IGF 1 induced IGFIR P . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transcriptional regulation of IGF 1 receptor gene expression by the PAX 3 FKHR oncoprotein . ^^^ In the present study the potential regulation of the IGF 1 receptor ( IGF 1 R ) gene by PAX 3 FKHR at the transcriptional level was investigated . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mediates IGF 1 and IGF 2 action on prenatal growth and IGF 1 action on postnatal growth . ^^^ Thus , IGF 2 is a true bifunctional ligand that is able to stimulate both insulin and IGF 1 receptor signaling , although with different potencies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There are several potential points of convergence between estradiol and IGF 1 receptor ( IGF IR ) signaling in the brain . ^^^ In addition , studies on adult ovariectomized rats given intracerebroventricular ( i . c . v . ) infusions with antagonists for ERs or IGF IR or with IGF 1 have shown that there is a cross regulation of the expression of ERs and IGF IR in the brain . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We hypothesize that the enhanced binding of IGF 1 at pH 5 . 8 is facilitated by increased association of IGFBP 3 at this pH and that the resulting cell associated IGF 1 is IGFBP 3 and not IGF IR bound . ^^^ Increased internalization and nuclear association of IGF 1 at pH 5 . 8 in the presence of IGFBP 3 was evident , yet cell proliferation was reduced by IGFBP 3 at both pH 5 . 8 and 7 . 4 indicating that IGFBP 3 cell associated IGF 1 does not signal the cell to proliferate and that the resulting transfer of bound IGF 1 from IGF IR to IGFBP 3 results in diminished proliferation . ^^^ Because IGF 1 receptor binding is affected by IGF binding proteins ( IGFBPs ) , we examined how pH impacted IGFBP 3 regulation of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : RT PCR was used to detect the mRNA expression of IGF 1 , IGF 2 , and IGF IR in T 24 cells and normal urothelial cells . ^^^ RESULTS : mRNA of IGF 1 , IGF 2 , and IGF IR were strongly expressed in serum free cultured T 24 cell line , whereas normal urothelial cells did not express these factors / receptors or only in trace levels ; knockdown of IGF IR by antisense ODN greatly inhibited the growth of bladder cancer cells and enhanced sensitivity and apoptosis of T 24 cells to MMC . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The late antral and atretic follicles in BERKO mice were characterized by a high level of expression of the androgen receptor ( AR ) and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF IR ) and ErbB 2 were expressed , respectively , in 50 and 70 % of the tumors from the OVX animals , whereas these genes were expressed in 100 % of the tumors from the intact rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report here that the intracellular domain of the Xenopus IGF 1 receptor is capable of binding to the Xenopus homolog of mammalian GIPC , a PDZ domain containing protein previously identified as a binding partner of G ( 1 ) specific GAP ( RGS GAIP ) . ^^^ This represents the first demonstration that GIPC 10 RGS GAIP complex acts positively in IGF 1 receptor signal transduction . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In both WT and alpha ERKO mice , IGF 1 treatment resulted in phosphorylation of uterine IGF 1 receptor ( IGF 1R ) and formation of an IGF 1R / insulin receptor substrate 1 / phosphatidylinositol 3 kinase signaling complex . ^^^ Together these data demonstrate that 1 ) functional signaling proximal to IGF 1R is maintained in the alpha ERKO mouse uterus , 2 ) ER alpha is necessary for IGF 1 induction of uterine nuclear proliferative responses , and 3 ) cross talk between IGF 1R and ER signaling pathways exists in vivo . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : Trastuzumab inhibited the growth of MCF 7 / HER2 18 cells , which overexpress HER2 / neu receptors and express IGF 1 receptors ( IGF IRs ) , only when IGF IR signaling was minimized . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
They had phosphorylation of the IGF 1 receptor beta subunit , phosphorylation of insulin receptor substrate ( IRS ) 1 , and association of the p 85 subunit ( phosphatidylinositol 3 kinase [ PI3K ] ) with the IGF 1 receptor and IRS 1 in D NOD cells in the basal state . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Their effects are mediated via binding to GH receptor ( GHR ) and IGF 1 receptor ( IGF IR ) in target tissues . ^^^ Growth hormone receptor and IGF 1 receptor immunoreactivity during orthodontic tooth movement in the prednisolone treated rat . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The significant association between high IGF 1R expression and death due to metastatic disease may be explained by the fact that IGF 1 is mainly produced in the liver , which is the preferential site for uveal melanoma metastases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Activation of insulin like growth factor 1 receptor ( IGF IR ) kinase is an important site of control of IGF 1 linked intracellular signaling pathways . ^^^ Cells expressing a catalytically inactive form of SHP 2 showed SHP 2 recruitment to SHPS 1 , but this did not result in SHPS 1 dephosphorylation , and there was a prolonged IGF IR phosphorylation response after IGF 1 stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : Reverse Transcription Polymerase chain reaction ( RT PCR ) was used to detect the gene expression of insulin like growth factor 1 ( IGF 1 ) and IGF receptors ( IGF IR and IGF IIR ) in vitro , and their regulation by RA in human cord blood lymphocyte ( CBL ) . ^^^ RESULTS : Significant upregulation of IGF 1 , IGF IR and IGF IIR mRNA was found at 6 24 hours in CBL incubated with physiologic concentrations of RA as compared to those without RA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : To investigate the number of follicles and insulin like growth factor 1 receptor ( IGF 1 R ) in stimulated cycles . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) binding protein 3 ( IGFBP 3 ) can stimulate apoptosis and inhibit cell proliferation directly and independently of binding IGFs or indirectly by forming complexes with IGF 1 and IGF 2 that prevent them from activating the IGF 1 receptor to stimulate cell survival and proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To examine whether autocrine IGF 1 signaling plays a role in the growth of these tumors , we used an animal model of uterine leiomyoma ( the Eker rat ) to investigate regulation of IGF 1 and the IGF 1 receptor ( IGF IR ) expression in tumors and normal myometrium . ^^^ The level of IGF IR mRNA in both tumor and non tumor tissues was found to inversely correlate with that of IGF 1 . ^^^ Autocrine stimulation of the IGF IR may , therefore , play a role in regulating the normal growth of the myometrium , and dysregulation of IGF 1 signaling could contribute to the neoplastic growth of uterine leiomyomas . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The somatomedin hypothesis proposed that GH stimulates hepatic IGF 1 production , which then regulates growth via IGF 1 receptor expressing chondrocytes in an endocrine fashion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : To observe the effect of Kidney replenishing Chinese herbs ( KRCH ) on insulin like growth factor 1 and its receptor ( IGF 1 / IGF 1R ) in androgen induced sterile rats ( ASR ) . ^^^ The level of serum IGF 1 was detected by radioimmunoassay , and IGF 1R by immunohistochemical method . ^^^ KRCH could lower the level of serum IGF 1 . ( 2 ) Level of IGF 1R in pancreas , liver , ovary and adrenal gland showed an opposite sequence to that of serum IGF 1 . ^^^ CONCLUSION : ASR shows a high IGF 1 level in serum and low IGF 1R level in main target organs , and KRCH could adjust the levels in certain degree . ^^^ From this , it is inferred that the ovulation effect of KRCH on ASR may come true partly by adjusting the level of IGF 1 / IGF 1R . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , the IGF 1 induced response was abolished by the IGF 1 receptor antagonist H 1356 in both groups , and by the nitric oxide synthase inhibitor L NAME in starch but not sucrose myocytes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : In vitro studies : 2 cell embryos were cultured in either 1 . 3 or 130 nmol / l IGF 1 ; or 500 nmol / l IGF 1 receptor ( IGF IR ) sense and antisense oligoprobes for 72 h . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin is known to bind to the IGF 1 receptor and to elicit significant responses in cartilage . ^^^ The observed effects of insulin were similar to effects of IGF 1 ( 0 . 05 microg / ml ) and were in agreement with the reported binding constants of IGF 1 and insulin at the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , testosterone increased in a dose dependent manner the abundance of IGF 1 receptor EGP . ^^^ We conclude that testosterone has a direct , local , GH independent effect on the EGP growth and IGF 1 receptor abundance . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Muscle specific inactivation of the IGF 1 receptor induces compensatory hyperplasia in skeletal muscle . ^^^ The insulin like growth factors IGF 1 and IGF 2 , through their cognate tyrosine kinase receptor ( IGF 1 receptor ) , are known to play a role in this process . ^^^ Here we show that MKR mice , which express a dominant negative IGF 1 receptor specifically in skeletal muscle , have marked muscle hypoplasia from birth to 3 weeks of age . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , high levels of IGF 1 and IGF IR have been shown in epithelial ovarian cancer , and IGF 1 stimulates the growth of ovarian cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This was not a direct effect of bp 1 01 because it did not bind to the receptor and did not activate tyrosine kinase activity in the presence of an anti IGF 1 receptor antibody . ^^^ This enhancement of hybrid receptor phosphorylation and glycogen synthesis by bp 1 01 peptide was diminished by preincubation with an inhibitory antibody for the alpha subunit of IGF 1 receptor ( alphaIR 3 ) . bp 1 01 stimulated the hybrid receptor phosphorylation response to IGF 1 , and this effect was inhibited by prior incubation of the cells with alphaIR 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The signalling capabilities of GFP IGF 1R in response to IGF 1 stimulation were investigated in transiently transfected fibroblasts . ^^^ In response to IGF 1 stimulation , the GFP IGF 1R became autophosphorylated and also activated the phosphatidylinositol 3 kinase and mitogen activated protein kinase pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Coprecipitation analysis revealed that alpha 6 integrin / IGF 1 receptor complexes were present and that their association was greatest in the equatorial zone , the region of the embryonic lens in which lens cells proliferate and then initiate their differentiation . ^^^ These results demonstrate that alpha 6 integrin function is required for the early stages of lens cell differentiation most likely through its association with the IGF 1 receptor and the activation of ERK . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , results from a detailed comparative analysis of growth patterns in double mutants lacking GPC 3 and also IGF 2 , IGF 1 , or the type 1 IGF receptor ( IGF1R ) provided conclusive genetic evidence inconsistent with the hypothesis that GPC 3 acts as a growth suppressor by sequestering or downregulating an IGF ligand . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study has systematically measured IGF1R binding affinities of IGF 1 , IGF 2 and 14 IGF analogues to a recombinant high affinity form of the IGF1R using BIAcore technology . ^^^ The analogues assessed could be divided into two groups : ( a ) those designed to investigate binding of IGF binding protein , which exhibited IGF1R binding affinities similar to those of IGF 1 or IGF 2 ; ( b ) those generated to probe IGF1R interactions with greatly reduced IGF1R binding affinities . ^^^ The relative binding affinities of IGF 1 analogues and IGF 1 for the IGF1R determined by BIAcore analysis agreed closely with existing data from receptor binding assays using cells or tissue membranes , demonstrating that BIAcore technology is a powerful tool for measuring affinities of IGFs for IGF1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A neutralizing IGF 1 antibody as well as IGF 1 receptor antibody also significantly but partially blocked DNA synthesis stimulated by high [ Pi ] ( e ) in a concentration dependent manner , indicating that IGF 1 at least in part mediated the high [ Pi ] ( e ) induced effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recently , we have shown that the survival promoting effect of ATA is transduced via activation of the IGF 1 receptor ( IGF IR ) signaling pathway . ^^^ The purpose of this study was to compare the ability of ATA and IGF 1 to activate the IGF IR signaling cascade and to correlate this ability to their survival potency . ^^^ MDA 231 cells were exposed to ATA or IGF 1 , up to 7 h , and the dynamics of activation of the IGF IR signaling cascade was evaluated . ^^^ Our results show that : 1 ) The amount of tyrosine phosphorylated IGF IR proteins was greater after exposure to ATA , compared with IGF 1 . 2 ) Two phosphorylated IGF IR beta subunits ( a 95 kDa and a 75 kDa ) were induced after exposure to ATA , whereas IGF 1 induced only the 95 kDa form . ^^^ Immunoprecipitation of both receptor forms by antibodies against the alpha subunit and against the carboxy terminus of the beta subunit of the IGF IR suggests that the 75 kDa form could be the beta chain truncated at the amino terminus above the alpha beta disulphide bridges . 3 ) The ATA activated IGF IR forms underwent slow dephosphorylation , compared with a rapid dephosphorylation of the IGF 1 activated receptor . 4 ) The insulin receptor substrate 1 / 2 associated PI3K , Shc proteins , and the kinases Akt and Erk1 / 2 , downstream mediators of the antiapoptotic signaling by IGF IR , were activated to a higher extent and for a longer time period by ATA , compared with IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Silver Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF 1 receptor ( IGF IR ) gene is located . ^^^ We measured both the maternal and cord blood levels of GH , IGF 1 , and IGF binding protein and performed an immunohistochemical study of IGF IR in the placenta to investigate whether these IGF related proteins were affected in this patient . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor type 1 ( IGF 1 ) receptor ( IGF IR ) , activated by its ligands IGF 1 and IGF 2 , can initiate several signal transduction pathways that mediate suppression of apoptosis , proliferation , differentiation , and transformation . ^^^ In both spontaneously immortalized and simian virus 40 T antigen transformed embryonic fibroblast cell lines derived from PTP 1B knockout mice , IGF 1 induced higher levels of IGF IR autophosphorylation and kinase activity than were induced in PTP 1B expressing control cells . ^^^ These findings demonstrate that PTP 1B can regulate IGF IR kinase activity and function and that loss of PTP 1B can enhance IGF 1 mediated cell survival , growth , and motility in transformed cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) is known to regulate a variety of cellular processes including cell proliferation , cell survival , cell differentiation , and cell transformation . ^^^ In several types of mammalian cells , RACK 1 interacted with IGF IR , protein kinase C , and beta 1 integrin in response to IGF 1 and phorbol 12 myristate 13 acetate stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The receptor is a monomeric glycoprotein with a molecular mass of 65 kDa and is antigenically related to the alpha chain of human type 1 IGF 1 receptor . ^^^ Activation of the IGF 1 receptor also leads to phosphorylation of an 185 kDa molecule that is homologous to the substrate of the insulin receptor present in human cells , the insulin receptor substrate 1 ( IRS 1 ) . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IL 1beta , IL 6 , and IFN gamma did not regulate IGF 1 , IGF 1 receptor ( R ) , or IGF binding proteins ( IGFBPs ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transcriptional regulation of IGF 1 receptor gene expression by novel isoforms of the EWS WT 1 fusion protein . ^^^ We have previously reported that the WT 1 protein represses the expression of the IGF 1 receptor gene , whereas the EWS ( 1 7 ) WT 1 ( 8 10 ) fusion protein activates IGF 1 receptor gene expression . ^^^ The chimeric transcription factors encoded by these various translocations differ in their DNA binding characteristics and their ability to transactivate the IGF 1 receptor promoter . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that the levels of dlk expression modulated signaling through the IGF 1 receptor , causing changes in the activation levels and kinetics of Extracellular Regulated Kinase / Mitogen Activated Protein Kinase ( ERK / MAPK ) that correlated with differentiation outcome . ^^^ However , the levels of expression of IGF 1 receptor , or the activation of Insulin Receptor Substrate 1 in response to IGF 1 , were not affected by the levels of dlk expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We designed and developed nine different calibration curves , based on recombinant DNA plasmid standards and established them on a constant real time PCR platform for the following factors : growth hormone receptor ( GHR ) , insulin like growth factor ( IGF ) 1 , IGF 1 receptor ( IGF 1R ) , IGF 2 , IGF 2 receptor ( IGF 2R ) , insulin receptor ( INSR ) , and IGF binding proteins ( IGF BP ) 1 , 2 and 3 . ^^^ Applicability of the method was shown by analysing mRNA levels in newborn calves : mRNA concentrations per gram tissue of mRNAs of IGF 1 , IGF 1R , IGF 2 , IGF 2R , GHR , INSR , and IGF BP 1 , 2 and 3 were all different between in liver and ileum and the traits all exhibited individual differences . . ^^^ Real time RT PCR quantification of insulin like growth factor ( IGF ) 1 , IGF 1 receptor , IGF 2 , IGF 2 receptor , insulin receptor , growth hormone receptor , IGF binding proteins 1 , 2 and 3 in the bovine species . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed that IGF 1 and 2 , IGFBP 1 to 6 and IGF IR were detected in the human corpus luteum throughout the luteal phase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , our analysis of early developmental processes in mammary tissue from mice carrying a targeted mutation in the IGF 1 receptor gene suggests that IGF dependent stimulation of cell cycle progression is more important to early mammary gland development than potential anti apoptotic effects . ^^^ The diminished ductal development that occurs in response to loss of the IGF 1 receptor is dramatically restored during pregnancy , whereas the ability of overexpressed IGF 1 to protect mammary cells from apoptosis does not occur if the mammary gland is induced to undergo forced involution . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate the occurrence of components of the insulin like growth factor ( IGF ) system during the resorption process of shedding human deciduous teeth , we investigated sections of 13 decalcified and paraffin embedded deciduous teeth immunohistochemically with antibodies against IGF 1 and 2 , six IGF binding proteins ( IGFBPs 1 6 ) and the IGF receptors IGF1R and IGF2R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We hypothesize that O 2 induced changes in the neonatal lung are mediated by Insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF 1R ) . ^^^ Western blots and immunohistochemistry were used to determine if hyperoxia stimulated IGF 1 and IGF 1R , and to identify the cell types involved . ^^^ Interaction of IGF 1 and IGF 1R is an important cell cell communication mechanism in the developmental and repair processes of hyperoxic neonatal lung injury . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 and IGF 1 receptor expression were assessed in vastus lateralis biopsies by real time PCR and Western blot analysis . ^^^ This was accompanied by an increase in IGF 1 receptor mRNA expression ( 86 . 8 + / 5 . 4 in CHF vs . 23 . 1 + / 1 . 8 arbitrary units in HS , p < 0 . 001 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Identification of insulin in the tear film and insulin receptor and IGF 1 receptor on the human ocular surface . ^^^ Frozen sections of human cornea ( n = 4 ) and conjunctiva ( n = 3 ) were incubated with anti insulin receptor and anti IGF 1 receptor antibodies and developed with a secondary antibody peroxidase conjugate . ^^^ CONCLUSIONS : To the best of the authors ' knowledge , this study represents the first demonstration of insulin in human tear film and the presence of insulin and IGF 1 receptor on the human ocular surface . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGFBP 5 augments the effects of IGF 1 by facilitating interaction of IGF 1 with the IGF 1 receptor tyrosine kinase . ^^^ IGFBP 5 caused a concentration dependent increase in [ ( 3 ) H ] thymidine incorporation and an increase in IGF 1 secretion that occurred independently of IGF 1 and the IGF 1 receptor tyrosine kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MAb aIR 3 ( 100 ng / ml ) to the IGF 1 receptor blocked the effects on [ 3H ] thymidine incorporation of strain , tIGF 2 , 17beta estradiol , and tIGF 1 . ^^^ In both human cell types ( unlike rat cells ) the effects of strain and IGF 2 as well as estradiol and IGF 1 can be blocked at the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Specific binding of ( 125 ) 1 IGF 1 to HUVEC monolayers was demonstrated , which was inhibited by aIR 3 , a specific antibody directed against the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Protein expressions of IGF 1 receptor ( IGF 1 R ) , estrogen receptor ( ER ) , and cell proliferation associated nuclear antigen ( ki 67 ) were analysed by streptavidin peroxide method in 40 cases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The proliferative action of insulin like growth factors ( IGF 1 and 2 ) is mediated via the type 1 IGF receptor ( IGF IR ) and is modulated by their association with high affinity binding proteins , IGFBP 1 to 6 . ^^^ Breast carcinoma derived cells ( MCF 7 ) were stimulated by des ( 1 3 ) IGF 1 or [ Gln ( 3 ) , Ala ( 4 ) , Tyr ( 15 ) , Leu ( 16 ) ] IGF 1 , two IGF analogues with intact affinity for IGF IR , but with weak or virtually no affinity for IGFBPs , then incubated with IGFBP 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Flies carrying mutations that reduce insulin signaling have a growth deficiency phenotype similar to that seen in mice with disruptions of genes encoding insulin like growth factors ( IGFs ) or the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both IGF 1 and IGF 2 , along with their receptor IGF 1R , are expressed early during embryogenesis , and the IGF 1R is present particularly in anterior and dorsal structures . ^^^ Overexpression of IGF 1 leads to anterior expansion of head neural tissue as well as formation of ectopic eyes and cement gland , while IGF 1 receptor depletion using antisense morpholino oligonucleotides drastically reduces head structures . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This lower responsiveness of ovaries from transgenic mice to gonadotropins was not associated with a decrease in FSH , LH or IGF 1 receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunoprecipitation studies with specific antibodies showed that both IGF IR genes are expressed and both receptors bind to IGFs and des ( 1 3 ) IGF 1 , but not to insulin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effects of synthetic progestagens on the mRNA expression of androgen receptor , progesterone receptor , oestrogen receptor alpha and beta , insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor in heifer tissues . ^^^ A dose dependent relationship between increasing MGA concentration and mRNA expression was observed in liver for AR and IGF 1 receptor , and in neck muscularity for IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 induced phosphorylation of IGF IR beta subunit , IRS 1 , mitogen activated protein kinase , Elk 1 , and Akt 1 as well as phosphatidylinositol 3 ' kinase activity was significantly attenuated when hepG 2 cells were pretreated with hrIGFBP 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The lower level of serum insulin like growth factor ( IGF ) 1 in MRs may be related to such a difference in hair cycle pattern , although the levels of IGF 1 and IGF 1 receptor mRNAs in the dorsal skin tissues were similar between MRs and WRs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunohistochemical localisation of growth hormone ( GH ) , GH receptor ( GHR ) , insulin like growth factor 1 ( IGF 1 ) and type 1 IGF 1 receptor , and gene expression of GH and GHR in rat pre antral follicles . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both granule and Purkinje neurons expressed insulin like growth factor 1 ( IGF 1 ) receptors , and deltaFADD mediated survival of granule neurons was inhibited by an IGF 1 receptor blocking antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It is hypothesized that in ISS an alteration of the signal transduction pathway between the GH receptor and IGFBP 3 synthesis results in a local imbalance with high IGFBP 3 levels and lower IGF 1 availability for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Upon conditional expression of c Myb in a NB cell line , we detected up regulation of IGF 1 , IGF 1 receptor , and insulin like growth factor binding protein 5 ( IGFBP 5 ) expression . ^^^ Together , these data suggest that the Myb binding independent transactivation of the IGFBP 5 promoter was due to the activation of the phosphatidylinositol 3 kinase / AKT pathway likely mediated by IGF 1 receptor dependent signals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cell cycle re entry required exogenous growth factor activation of the IGF IR by insulin or IGF 1 . ^^^ Activation of the TGFalpha autocrine loop is downstream of IGF 1 receptor activation during mitogenesis in growth factor dependent human colon carcinoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin receptor ( IR ) and IGF 1 receptor ( IGF IR ) are structurally and functionally related and belong to the tyrosine kinase receptor family . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : Insulin like growth factor 1 ( IGF 1 ) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF 1 receptor . ^^^ This finding is consistent with experimental data that indicate that IGFBP 3 can inhibit cellular proliferation and induce apoptosis independent of IGF 1 and the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
High plasma IGF 1 levels predispose to prostate cancer , but there is no consensus regarding IGF1R expression in primary and metastatic prostate cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To examine the insulin growth factor ( IGF ) 1 / insulin intracellular signaling pathways involved in GLUT 8 translocation , IGF 1 receptor ( IGF 1R ) expression was decreased in the blastocysts with antisense oligonucleotides . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tissue specific knockout of the insulin receptor ( betaIRKO ) or IGF 1 receptor ( betaIGFRKO ) in pancreatic beta cells leads to altered glucose sensing and glucose intolerance in adult mice , and betaIRKO mice show an age dependent decrease in islet size and beta cell mass . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and IGF 2 stimulate cancer cell proliferation via interaction with the type 1 IGF receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dephosphorylation of basal Ser / Thr sites on F IRS 1 also significantly reduced tyrosine phosphorylation by the IGF 1 receptor . ^^^ However , dephosphorylation of F IRS 2 significantly increased phosphorylation by the IGF 1 receptor , suggesting that basal phosphorylation of IRS 2 has divergent effects on its interaction with the insulin and IGF 1 receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PCR analyses of the embryonic libraries for specific genes revealed transcripts for genes including housekeeping genes ( GAPDH and beta actin ) , developmental genes ( OCT 4 , IGF 1 receptor and homeodomain sequences ) and genes coding for metabolic and protective enzymes ( manganese superoxide dismutase , glutamine synthetase , flavin containing mono oxygenase , glutamate dehydrogenase , alpha 2 macroglobulin ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
DHEA resulted in a significant reduction in IGF 1 receptor protein levels . ^^^ In contrast to IGF 1 receptor , IGF 1 binding protein 2 levels were unaffected by DHEA treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression patterns of mRNAs encoding IGF 1 , IGF 2 , type 1 IGF receptor ( IGF 1R ) , and the IFG binding proteins ( IGFBP ) 1 , 3 and 5 were determined from autoradiographs . ^^^ None of the parameters measured differed between heifers with or without the presence of an embryo . mRNAs encoding IGF 1 and IGF 1R were present in the mucosa and muscle of all three oviductal regions , and the highest value of IGF 1 mRNA was measured in heifers on day 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Leptin also increased the abundance of the insulin like growth factor ( IGF ) 1 receptor and IGF 1 receptor messenger RNA ( mRNA ) within the chondrocytes and the progenitor cell population . ^^^ Some of its effects on the growing bone may be mediated by the IGF system via regulation of IGF 1 receptor expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Retroviral expression of a kinase defective IGF 1 receptor suppresses growth and causes apoptosis of CHO and U 87 cells in vivo . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Results of this study show that the majority of cases examined were characterized by the abundant presence of the receptor for IGF 1 ( IGF IR ) protein ( 16 of 20 cases ) , and its major signaling molecule , insulin receptor substrate 1 ( IRS 1 ; 15 of 20 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The biological actions of the insulin like growth factors ( IGFs ) are mediated primarily by the IGF 1 receptor ( IGF IR ) , and the IGF family has been highly conserved throughout vertebrate evolution . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of a human IGF 1 receptor in 32D / IRS 1 cells also results in nuclear translocation of IRS 1 and IL 3 independence . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor ( IGF ) 1 and the type 1 IGF 1 receptor are important regulators of vascular function that may contribute to cardiovascular disease . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Antibodies against the insulin like growth factor 1 ( IGF 1 ) or the IGF 1 receptor ( IGF IR ) directly initiate a rapid ( within 6 h ) hypertrophy of isolated adult rat ventricular cardiomyocytes cultured in the absence of serum . ^^^ Anti IGF 2 antibody inhibits the cardiomyocyte hypertrophy induced by anti IGF 1 and anti IGF IR antibodies or by genistein . ^^^ Hypertrophy of cultured adult rat ventricular cardiomyocytes induced by antibodies against the insulin like growth factor ( IGF ) 1 or the IGF 1 receptor is IGF 2 dependent . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inactivating mutations leading to growth retardation in humans have been identified in several pituitary transcription factor genes ( HESX 1 , PITX 2 , LHX 3 , PROP 1 , POU1F1 ) as well as in genes encoding the growth hormone releasing hormone receptor ( GHRH R ) , the G ( s ) protein alpha subunit ( GNAS 1 ) , growth hormone itself ( GH 1 ) , the growth hormone receptor ( GHR ) , and in a single case each , the insulin like growth factor 1 ( IGF 1 ) and the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSIONS : : Our findings are consistent with the hypothesis that IGFBP 6 inhibits cell growth by binding to endogenously produced IGF 2 , thereby preventing IGF 2 from interacting with the IGF 1 receptor to stimulate cellular proliferation by an autocrine mechanism . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Elevated levels of IGF 1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The fact that insulin can influence the primordial to primary follicle transition at low concentrations ( i . e . 5 ng / ml ) and that IGF 1 has no effect suggests that insulin is acting at the insulin receptor , not the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The inhibition of mIRS 3 promoter by wild type p 53 , and its de repression by tumor derived p 53 mutants , appears to be similar to that previously reported for the IGF 1 receptor promoter , suggesting a common role of these two genes in p 53 mediated cell growth and differentiation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recently , based on a study in rats with chronic renal failure ( CRF ) , it has been suggested that IGF 1 resistance in uremia may be caused in part by defective IGF 1 receptor autophosphorylation and tyrosine kinase activity . ^^^ Accordingly , we examined IGF 1 receptor function in rats with uremia of increasing duration and in pair fed sham operated controls . ^^^ After 6 days of prolonged ARF , kidney IGF 1 receptor binding increased twofold , while IGF 1 stimulated receptor phosphorylation and tyrosine kinase activity were unchanged . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Combined inactivation of insulin receptor ( Insr ) and Igf 1 receptor ( Igf1r ) , but not of either receptor alone , resulted in a 90 % decrease in the size of the exocrine pancreas , because of decreased cellular proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
One male ( 20 yr ) had a partial deletion of the IGF 1 gene , and one female ( 14 yr ) had a single allele deletion of the IGF 1 receptor gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : The activation of Erk 1 and 2 in mesangial cells ( MCs ) and isolated glomeruli ( IG ) was investigated by immunoprecipitation and Western blotting during activation of the IGF 1 receptor in the presence or absence of BK and of protein kinase C ( PKC ) , tyrosine kinase and phosphatase selective inhibitors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Within 72 h from diabetes onset , IGF 1 mRNA levels in epiphyseal growth plate homogenates decreased whereas IGF 1 receptor mRNA levels increased in diabetic animals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Previous studies have suggested that antiestrogens inhibit MCF 7 cell proliferation by alteringthe expression or activity of components of the insulin like growth factor 1 ( IGF 1 ) signaling pathway , including IGF 1 receptor , insulin receptor substrate 1 , and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Competition binding studies with DES ( 1 3 ) IGF 1 and R ( 3 ) IGF 1 , which display high affinity for the IGF 1 receptor and low affinity for IGF binding proteins ( IGFBPs ) , were performed to distinguish [ ( 125 ) 1 ] IGF 1 binding to IGF 1 receptors and IGFBPs . ^^^ In contrast , [ ( 125 ) 1 ] IGF 1 binding in the anterior pituitary was not displaced by DES ( 1 3 ) IGF 1 and R ( 3 ) IGF 1 , suggesting binding to an IGF binding site that is different from the IGF 1 receptor . ^^^ Binding affinity of IGF 1 to this site was about 10 fold lower than for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factors ( IGFs ) 1 and 2 are critical regulators of cell proliferation and differentiation and most of the growth promoting properties of both ligands are mediated by IGF 1 receptor ( IGF IR ) . ^^^ Abundant expression of IGF 1 , IGF 2 and IGF IR was demonstrated in resting cells and exogenous IGF 1 and IGF 2 increased 3H thymidine incorporation in a dose dependent manner . ^^^ Furthermore , also IGF 1 and IGF 2 induced DNA synthesis was significantly suppressed by anti IGF IR mAb . ^^^ During megakaryocytic differentiation , expression of IGF IR increased during first 12h , but after that the expression started to decrease together with IGF 1 . ^^^ Taken together , our data suggest that autocrine production of IGF 1 and IGF 2 may via IGF IR play a significant role in the growth and megakaryocytic differentiation of K 562 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Taken together , these data reveal that endogenous FKHRL 1 is a downstream substrate of PI3K / Akt in IGF 1 receptor signaling in hippocampal neurons and suggest that the phosphorylation of this transcription factor may play an important role in the neuronal survival properties of IGF 1 . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the contrary , the functional link between caveolin 1 and IGF 1 Receptor ( IGF IR ) remains largely unknown . ^^^ Here we show that ( 1 ) IGF IR colocalizes with caveolin 1 in the lipid rafts enriched fractions on plasmamembrane in R IGF IR ( WT ) cells , ( 2 ) IGF 1 induces caveolin 1 phosphorylation at the level of tyrosine 14 , ( 3 ) this effect is rapid and results in the translocation of caveolin 1 and in the formation of membrane patches on cell surface . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Western blotting and in situ hybridization revealed significant reductions in the expression of IGF 1 , IGF 2 , IGF IR and IR preceding ( 2 months ) and accompanying ( 8 months ) the functional cognitive impairments and the apoptotic neuronal loss in hippocampus . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , we investigated age related changes in IGF 1 receptor localization in the cerebral cortex and hippocampus of Sprague Dawley rats using immunohistochemistry . ^^^ In aged rats , there was a significant increase in IGF 1 receptor immunoreactivity in the pyramidal cells in the same cortical regions . ^^^ Levels of IGF 1 receptor protein increased substantially with age in the CA 3 area of the hippocampus . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By binding to Hybrid Rs ( A ) , insulin activated the IGF 1 half receptor beta subunit and the IGF IR specific substrate CrkII . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We also examined IGF 1 receptor numbers ( Scatchard analysis ) and IGF 2 production and release ( by Western blot ) in IGF II / IGF IR mRNA positive and negative lung carcinomas . ^^^ RESULTS : Thirty two tumors were positive for IGF 1 , 39 for IGF 2 , 48 for IGF IR , and 35 for IGFBP 4 mRNA . ^^^ BACKGROUND : Perturbation in a level of any peptide from insulin like growth factor ( IGF ) family ( ligands , receptors , and binding proteins ) seems to be implicated in lung cancer formation ; IGF ligands and IGF 1 receptor through their mitogenic and anti apoptotic action , and the mannose 6 phosphate / insulin like growth factor 2 receptor ( M 6 P / IGF IIR ) possibly as a tumor suppressor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There was no significant difference between NBS and NBS 1 complemented cells in activation of major downstream pathways of IGF IR upon IGF 1 stimulation , including phosphatidylinositol 3 ( ' ) kinase ( PI 3 K ) and mitogen activated protein kinase ( MAPK ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These data suggested the existence of IGF 1 resistance possibly caused by impairment of the IGF 1 receptor ( IGF IR ) or altered IGFBPs . ^^^ Affinity crosslinking studies using [ 125I ] IGF 1 showed normal sized IGF IR ligand complexes . ^^^ Mutation analysis of the complete coding regions of the IGF 1 and IGF IR genes showed no evidence of genetic alterations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This effect was inhibited by the IGF 1 receptor neutralizing antibody aIR 3 , the PI 3K inhibitor wortmannin , and the heat shock protein 90 chaperone inhibitor geldanamycin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , insulin like growth factor 1 receptor ( IGF IR ) endocytosis is facilitated by beta arrestin 1 , and internalization is necessary for IGF 1 stimulated mitogen activated protein ( MAP ) kinase activation . ^^^ We also found a marked decrease in the association of beta arrestin 1 with the IGF IR and a 55 % inhibition of IGF 1 stimulated MAP kinase phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In reverse transcription polymerase chain reaction experiments , both the alcoholic and control animals expressed the IGF 1 receptor ( IGF 1R , alpha subunit ) and IGF 1 mRNAs in approximately equal amounts . ^^^ However , in the alcoholic cardiomyocyte protein preparations , there was a higher basal level of IGF 1R autophosphorylation of its internal tyrosine kinase domain , and IGF 1 activated autophosphorylation was reduced in the alcoholic protein preparations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
EN only very weakly transformed so called R murine fibroblasts derived from mice with a targeted disruption of the IGF 1 receptor gene ( IGFRI ) , but transformation activity was fully restored in R cells engineered to re express IGFRI ( R+ cells ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
TNF alpha and IL 1beta act by inhibiting the IGF 1 receptor from tyrosine phosphorylating insulin receptor substrate 1 without affecting tyrosine kinase activity of the IGF IR itself . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Key intracellular signaling mechanisms associated with ligation of the primary IGF 1 receptor are highlighted to illustrate the mechanisms by which IGF 1 may promote muscle hypertrophy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition to cytomorphological criteria , expression of ER alpha and beta , RAR alpha and beta , and IGF 1 receptor in the nucleus should be examined . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
First , a variety of techniques were used to determine if IGF 1 and the IGF 1 receptor ( IGF IR ) are expressed in the retina . ^^^ Reverse transcriptase polymerase chain reaction , screening a retinal cDNA library and Northern analysis showed that genes encoding IGF 1 and IGF IR are expressed in the retina of goldfish . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibition of DNA synthesis was completely reversed by an IGF 1 receptor neutralizing antibody , alphaIR 3 , indicating that IGF 1 receptor activation is involved in its inhibitory effect . ^^^ Attenuation of the p44 / 42 mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3 ' kinase ( PI 3 ' kinase ) pathways downstream of the IGF 1 receptor using the inhibitors PD 98059 and LY 294002 , respectively , partially reversed IGF 1 induced inhibition . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of an IGF 1 receptor dominant negative mutant induces apoptosis , inhibits tumorigenesis and enhances chemosensitivity in Ewing ' s sarcoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The k / o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF 1 receptor but markedly reduced basal mRNA levels of the osteoblast markers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The immunoreactive products of IGF 1 , IGF IR , TGF beta , TGF beta R , Fas and Fas L could be seen in the granulosa cells of healthy antral follicles . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In adult rats , no immunoreactivity for IGF 1 receptor was found in any layers of cerebellar cortex . ^^^ In contrast , IGF 1 receptor immunoreactivity was found in the cerebellar cortex of aged rats . ^^^ The cerebellar output neurons showed little immunoreactivity for IGF 1 receptor in the nucleus medialis , interpositus and lateralis of adult rats . ^^^ In aged cerebellar nuclei , IGF 1 receptor immunoreactivity was observed in the surrounding neuropil . ^^^ The first demonstration of upregulation of IGF 1 receptor in aged rat cerebellum suggests that IGF 1 may promote the survival of a degenerated population of the Purkinje neurons by increases in IGF 1 receptor expression during aging . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In an attempt to uncover the molecular mechanisms underlying their divergent functions , we compared insulin receptor ( IR ) and IGF 1 receptor ( IGF 1R ) regulation of gene expression by microarray analysis , using 3T3 L 1 cells expressing either TrkC / IR or TrkC / IGF 1R chimeric receptors to ensure the highly selective activation of each receptor tyrosine kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Therefore , we investigated the local expression of IGF 1 and IGF 1 type 1 receptor ( IGF IR ) in 50 paired normal colon and carcinoma samples . ^^^ IGF IR mRNA was present in all samples , whereas IGF 1 mRNA was detected in only 30 normal ( 60 % ) and 27 tumour ( 54 % ) biopsies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This hypothesis is supported by a gene dose dependent decrease in IGF 1 receptor ( IGF IR ) phosphorylation . ^^^ These results indicate that IGF 1 ' s actions on wv granule neurons are normally inhibited by excess IGFBP 5 , and sufficient IGF 1 receptor activation rescues wv granule neurons via stimulating the Akt signaling pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Embryonic transcripts for insulin like growth factors 1 and 2 ( IGF 1 and 2 ) , their receptors ( IGF 1r and 2r ) , facilitative glucose transporters 1 and 3 ( Glut 1 and 3 ) , and interferon tau ( IFN tau ) were determined by real time quantitative PCR ( TaqMan ) ; gender diagnosis was performed on day 16 concepti only . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This agent induced the recovery of both the expression of PDGF receptor beta and IGF 1 receptor beta and the phosphorylation of p42 / 44 mitogen activated protein kinase ( MAPK ) and Akt under stimulation with either PDGF BB or IGF 1 , which were downregulated by N acetyl L cysteine . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunoreactivity for receptors ( R ) for IGF 1 and FGF 2 ( IGF 1R , FGFR 1 , and FGFR 3 ) was most pronounced in chondroblasts and hypertrophic chondrocytes , while FGFR 2 immunoreactivity was strongest in the articular and prechondroblastic zones . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we examined the expression of insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF IR ) in dorsal root ganglia ( DRG ) neurons in two rodent models of nerve injury : sciatic nerve axotomy and streptozotocin induced ( STZ ) painful diabetic neuropathy . ^^^ There is a significant down regulation in the expression of IGF 1 and IGF IR in the small DRG neurons of STZ rats by 59 % and 71 % , respectively . ^^^ A parallel reduction in expression is shown in axotomized < 25 microm diameter DRG neurons for IGF 1 ( 47 % ) but not for IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor expression was measured by RT PCR and IGF 1 receptor binding sites were assayed by radiolabeled IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this report , we have identified a new mechanism of apoptosis inhibition by amphiregulin through an IGF 1 dependent survival pathway in non small cell lung cancer ( NSCLC ) cells : amphiregulin activates the IGF 1 receptor that in turn induces the secretion of amphiregulin and IGF 1 . ^^^ IGF 1 receptor inhibitor AG 1024 as well as epidermal growth factor receptor inhibitors AG 556 and ZD 1839 restore apoptosis in H 322 cells cultured in H 358 conditioned medium . ^^^ H 358 conditioned medium and amphiregulin induce IGF 1 receptor phosphorylation in H 322 cells , which is prevented by anti amphiregulin neutralizing antibody but not by AG 556 or ZD 1839 . ^^^ Finally , IGF 1 receptor inhibitor blocks amphiregulin and IGF 1 release by H 358 cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and its cognate receptor , the type 1 IGF receptor ( IGF1R ) , as well as high affinity IGF binding proteins ( IGFBP ) that modulate IGF 1 actions , are expressed throughout the course of brain development . ^^^ Mutant mice with ablated IGF 1 and IGF1R expression , as well as those with overexpression of IGFBPs capable of inhibiting IGF actions , exhibit brain growth retardation with a variety of growth deficits . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here , we discuss recent progress in understanding the structure function relationships of the insulin and insulin like growth factor 1 ( IGF 1 ) receptors , their mechanism of activation and their implications for the design of insulin receptor agonists for diabetes therapy and IGF 1 receptor antagonists for cancer therapy . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : Truncated IGF 1 receptors ( IGF Ir / tf ; 482 and 950 amino acids long , respectively [ IGF Ir / 482st and IGF Ir / 950st ] ) were cloned into tetracycline regulated vectors and recombinant adenoviruses and then studied in colorectal cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Purpose and Experimental Design : Insulin like growth factors ( IGFs ) 1 and 2 and their principle receptor , IGF 1 receptor ( IGF IR ) , are frequently expressed in human colon cancers and play a role in preventing apoptosis , enhancing cell proliferation , and inducing expression of vascular endothelial growth factor ( VEGF ) . ^^^ RESULTS : IGF 1 increased VEGF expression in parental and vector transfected cells , whereas IGF 1 induction of VEGF mRNA and protein was abrogated in IGF IR DN cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
EtOH did not alter the total amount or tyrosine phosphorylation of the insulin receptor , IGF 1 receptor , insulin receptor substrate ( IRS ) 1 , or protein kinase B ( PKB ) / Akt under basal or hormone stimulated conditions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factors and their principal receptor , IGF 1 receptor ( IGF IR ) , are frequently expressed in human colon cancers and play a role in preventing apoptosis , enhancing cell proliferation , and inducing expression of vascular endothelial growth factor ( VEGF ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By RT PCR analysis , mRNAs of IGF 1 , 2 , IGF 1 receptor ( IGF IR ) , and IGF binding proteins ( IGFBPs ) 2 , 3 , 4 , 5 , and 6 were found to be expressed in the olfactory mucosa . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Short term insulin treatment and aortic expressions of IGF 1 receptor and VEGF mRNA in diabetic rats . ^^^ In contrast , the mRNA for the aortic IGF 1 receptor was increased in diabetics and further increased in insulin treated diabetics . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expression of IGF 1 , c fos , NGF and the receptors p 75 and IGF 1R were determined at the protein and mRNA levels in sciatic nerve distal to the crush site by immunoblotting and semi quantitative RT PCR . ^^^ In situ hybridization was performed to assess the cellular localization of IGF 1 , NGF , p 75 , and IGF 1R mRNA and immunohistochemistry served to localize the source of p 75 and IGF 1R protein expression . ^^^ IGF 1R was expressed in Schwann cells and its expression was asynchronous to IGF 1 expression in type 1 rats but remained synchronous with IGF 1 in control and type 2 animals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor gene is a good SRS candidate gene because the biological effects of the major growth factors IGF 1 and 2 are transmitted through the IGF 1 receptor during pre and postnatal growth . ^^^ After reverse transcription of RNA , 19 overlapping cDNA fragments encompassing the whole IGF 1 receptor coding sequence were PCR amplified and screened for mutations by single strand conformation analysis ( SSCP ) . ^^^ All single base exchanges ( C948A , C2343T , G3174A and G3915A ) were silent variants of the IGF 1 receptor gene , two of which were also present in control individuals . ^^^ In conclusion , for the first time , the complete coding region of the IGF 1 receptor gene was screened for mutations in patients with SRS . ^^^ Our data do not support the suggestion that the IGF 1 receptor is frequently involved in the pathogenesis of SRS . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , reports from multiple laboratories confirm a critical role for the IGF 1 receptor ( IGF IR ) in the process of cellular transformation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , infusion of a selective IGF 1 receptor antagonist abrogates HIF 1alpha accumulation after cardiac arrest and resuscitation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Weaning reduced ( P < 0 . 05 ) both IGF IR mRNA levels and specific binding of IGF 1 in the jejunum in both groups at day 34 , but only in SEW pigs ( P < 0 . 05 ) at day 3 post weaning . ^^^ This study documents the changes in IGF 1 , IGF IR , and IGFBP mRNA abundance , and in IGF 1 binding during post weaning adaptation of the intestine in early weaned pigs . ^^^ In addition , the relative differences observed in intestinal expression of IGF 1 , IGF IR , and in IGF 1 binding between the post weaning environments are consistent with previous observations in a companion study indicating that segregated early weaning enhances post weaning intestinal maturation in pigs . . ^^^ The objective of this study was to investigate changes in gene expression of intestinal IGF 1 , IGFBPs , and IGF 1 receptor in pigs in response to weaning and different rearing environment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Analysis of IGF 1 receptor ( IGF IR ) and HGF SF ( c met ) receptor expression showed significantly higher expression of both receptors in normal liver compared with an HCC specimen . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have shown that recruitment of the tyrosine phosphatase Src homology 2 containing phosphotyrosine phosphatase 2 ( SHP 2 ) to the IGF 1 receptor ( IGF IR ) is an important determinant of the duration of IGF IR phosphorylation . ^^^ Following an overnight exposure of smooth muscle cell cultures to echistatin , the addition of IGF 1 was accompanied by rapid dephosphorylation of IGF IR compared with cells exposed to media alone . ^^^ In contrast to the usual physiologic situation in which following IGF 1 exposure SHP 2 is recruited to IGF IR via SHP 2 substrate 1 ( SHPS 1 ) in the presence of echistatin , SHPS 1 was not used for SHP 2 recruitment . ^^^ The alphaVbeta 3 integrin regulates insulin like growth factor 1 ( IGF 1 ) receptor phosphorylation by altering the rate of recruitment of the Src homology 2 containing phosphotyrosine phosphatase 2 to the activated IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Overgrowth and trisomy 15q26 . 1 qter including the IGF 1 receptor gene : report of two families and review of the literature . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : High concentrations of insulin like growth factor ( IGF ) 1 and IGF 2 have been demonstrated in human colonic adenocarcinomas and exert mitogenic effects through paracrine / autocrine interactions with the IGF 1 receptor ( IGF IR ) . ^^^ IGF 1 affinity crosslinking and sodium dodecyl sulfate polyacrylamide gel electrophoresis displayed specific bands corresponding to the size of the normal alpha subunit of the IGF IR that were more intense in carcinomatous samples . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 ( 100 ng / ml ) and IGF 2 ( 100 ng / ml ) decreased DA and NE content to approximately 35 % and approximately 25 % of control , respectively . [ Leu 27 ] IGF 2 , which binds to the IGF 1 receptor with markedly decreased affinity , did not reduce catecholamine levels , indicating that the effect is likely to be mediated by the IGF 1 receptor . ^^^ These results indicate that IGFs decrease catecholamine content in PC 12 cells via the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , the effect of estradiol on the signaling pathways of IGF 1 receptor has been assessed in the hypothalamus of young adult ovariectomized rats , using specific antibodies for the phosphorylated forms of extracellular signal regulated kinase ( ERK ) 1 and ERK 2 and Akt / protein kinase B ( Akt / PKB ) . ^^^ These findings suggest that estrogen effects in the hypothalamus may be mediated in part by the activation of the signaling pathways of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Evidence from in vitro and animal studies suggests that overexpression of IGFs by cancer cells and / or the nearby stroma as well as the type IGF 1 receptor by the cancer cells may play a significant role in establishing a transformed phenotype in an increasing number of malignancies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 ( 10 nM ) inhibited K ( + ) as well as veratridine evoked ACh release from rat hippocampal slices and the effect is possibly mediated via the activation of a typical IGF 1 receptor and the subsequent phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we used coimmunoprecipitation to show that Annexin 2 was bound to insulin and insulin like growth factor 1 ( IGF 1 ) receptors in PC 12 cells and NIH 3T3 cells overexpressing insulin ( NIH 3T3 ( IR ) ) or IGF 1 receptor ( NIH 3T3 ( IGF 1R ) ) . ^^^ Stimulation of insulin and IGF 1 receptors by insulin caused a temporary dissociation of annexin 2 from these receptors , which was accompanied by an increased amount of extracellular annexin 2 detected in the media of PC 12 , NIH 3T3 ( IR ) , and NIH 3T3 ( IGF 1R ) cells but not in that of untransfected NIH 3T3 cells . ^^^ Tyrphostin AG 1024 , a tyrosine kinase inhibitor of insulin and IGF 1 receptor , was shown to inhibit annexin 2 secretion along with reduced receptor phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) mediated signals are known to be involved in cell growth and transformation and prevention of apoptosis . ^^^ In this study , we demonstrated the coexpression of IGF 1 and IGF IR in human esophageal carcinoma tissues . ^^^ Autokinase activity of IGF IR in these cells can be triggered by the exogenous addition of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The dynamics of IGF 1 receptor ( IGF IR ) activation were examined in freshly isolated rat hepatocytes . ^^^ IGF 1 did not activate the IGF IR . ^^^ However , des ( 1 3 ) IGF 1 , which weakly binds IGF binding protein 3 ( IGFBP 3 ) , induced IGF IR phosphorylation . ^^^ In contrast with the inactivity of IGF 1 , epidermal growth factor ( EGF ) induced the tyrosine phosphorylation of the IGF IR in parallel with EGF receptor phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 receptor ( IGF 1R ) expression is augmented on T cells upon ligation of CD 28 , and this promotes IGF 1 mediated protection from Fas induced cell death for up to 6 days . ^^^ To determine the mechanism of action of IGF 1R in T cell expansion , we investigated the signalling pathways activated by IGF 1 in T cells and in Jurkat cells . ^^^ Jurkat / IGF 1R cells exhibited enhanced constitutive Akt phosphorylation compared with mock transfected controls , but IGF 1 induced transient phosphorylation of MKK 4 , JNKs , and c Jun . ^^^ Inhibition of PI 3 kinase activity and Akt phosphorylation with LY 294002 totally suppressed IGF 1 mediated protection from Fas killing in activated T cells , but only partially suppressed IGF 1 mediated protection in Jurkat / IGF 1R cells . ^^^ However , either dicumarol in T cells or a dominant negative JNK 1 ( APF ) in Jurkat / IGF 1R cells greatly suppressed IGF 1 mediated protection from Fas killing . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Trophoblast cells were treated with IGF 1 in the presence or absence of RGD peptide and an antibody against alpha subunit of IGF 1 receptor ( alphaIR 3 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Nuclear activation through IGF 1 receptor mediated pathways prior to exposing sarcoma cells to doxorubicin altered the pattern of response to doxorubicin with enhanced mitogenesis ( > 2 fold ) and blunted doxorubicin cytotoxicity ( > 10 % change in IC 50 ) . ^^^ These data suggest that activation of IGF 1 receptor in sarcoma cells is a potential mechanism for tumor resistance to doxorubicin . ^^^ Inhibition of IGF 1 receptor activation represents a novel approach to enhance the degree and duration of response to traditional chemotherapy against soft tissue sarcoma . . ^^^ Insulin like growth factor 1 receptor ( IGF 1 R ) activation may contribute to resistance to chemotherapy in mesenchymal neoplasia . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
At 2 and 7 days after ischemia , serum urea nitrogen and histological damage score , cell proliferation , apoptosis , neutrophil infiltration , and IGF 1 receptor mRNA in kidneys were analyzed . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Microgravity decreased the mRNA levels of insulin like growth factor 1 ( IGF 1 ) and increased reciprocally the IGF 1 receptor mRNA levels , as compared to the ground ( 1 10 g ) control . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate the mechanism of severe impairment of insulin action in type B insulin resistance , we extracted IgG from the serum of a patient with type B insulin resistance ( B IgG ) and analyzed the inhibiting effect of B IgG not only on insulin signaling but also on IGF 1 signaling in Chinese hamster ovary ( CHO ) cells expressing human insulin receptor or human IGF 1 receptor . ^^^ Preincubation with 1 mg / ml B IgG prevented insulin induced phosphorylation of insulin receptor and insulin receptor substrate 1 ( IRS 1 ) but did not alter the IGF 1 induced phosphorylation of the IGF 1 receptor and IRS 1 . ( 125 ) 1 insulin binding was inhibited by 93 % after preincubation with B IgG at 37 degrees C and was recovered up to 50 % of the control value by acid washing . ^^^ This effect of B IgG was specific for the insulin receptor with no effect on either IGF 1 receptor or IRS 1 , as reflected by the IGF 1 effectiveness on glycemic control in this patient . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The transduction of both ad IGF IR / 950 and ad IGF IR / 482 could blunt the growth stimulatory effect of IGF 1 on human lung cancer cell lines . ^^^ Both ad IGF IR / 950 and ad IGF IR / 482 effectively blocked IGF 1 induced Akt kinase activation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both medulloblastoma cell lines and medulloblastoma biopsies are characterized by the abundant presence of the IGF 1 receptor ( IGF IR ) and its major signaling molecule , insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The strong antiapoptotic activity of IGF IR has been recognized as critical in IGF 1 dependent tumorigenesis , however , the impact of other IGF IR functions , such as regulation of cell cell and cell matrix adhesion are also increasingly acknowledged . ^^^ Role of the IGF 1 receptor in the regulation of cell cell adhesion : implications in cancer development and progression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that alterations of IGF 1 levels or IGF 1 receptor signal transduction modulate the antineoplastic actions of COX 2 inhibitors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Serial lung tissue sections from a biopsy database were immunohistochemically stained for IGF 1 , IGF 1 receptor , CD 68 , alpha smooth muscle actin , collagens 1 and 3 , and proliferating cell nuclear antigen . ^^^ Our results show enhanced staining of IGF 1 and IGF 1 receptor , collagens 1 and 3 , smooth muscle actin , CD 68 , and proliferating cell nuclear antigen in FP ARDS compared with control lung sections . ^^^ In FP ARDS specimens , prominent staining of IGF 1 and IGF 1 receptor was seen in alveolar and interstitial macrophages as well as in a variety of mesenchymal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MATERIAL / METHODS : The experimental strategy involved combining trastuzumab treatment and reduction of IGF 1R signaling through incremental heat induced expression of the dominant negative IGF 1 receptor 486 / STOP under the control of the heat sensitive Drosophila HSP 70 promoter , in HER2 / erbB2 overexpressing MCF7her18 breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Changes in IGF 1 receptor and IGF 1 mRNA during differentiation of 3T3 L 1 preadipocytes . ^^^ We investigated the expression of IGF 1 receptor and IGF 1 RNA messenger during 3T3 L 1 preadipocyte differentiation . ^^^ Levels of IGF 1 receptor decreased in the mature adipocytes compared to cells before the initiation of differentiation . ^^^ We propose an autocrine and / or paracrine action of IGF 1 in this adipocyte differentiation model , where IGF 1 produced by the differentiating preadipocytes acts over their adjacent cells and , in this way , diminishes the expression of IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In light of earlier studies showing that the activation of the insulin like growth factor 1 receptor ( IGF IR ) exerts a strong neuroprotective effect , we investigated the ability of IGF 1 to protect neuronal cells from HIV infected macrophages . ^^^ Furthermore , we demonstrate that IGF 1 rescues differentiated neurons from both HIV / CM and TNFalpha induced damage and that IGF 1 mediated neuroprotection is strongly enhanced by overexpression of the wt IGF IR cDNA and attenuated by the antisense IGF IR cDNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Histone 4 transcripts , IGF 1 receptor expression , and histochemical staining for chondroclasts were decreased in Nx D animals . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The biological actions of the insulin like growth factors , IGFI and IGFII , are mediated by their activation of the IGFI receptor ( IGFIR ) , a transmembrane heterotetramer linked to the RAS RAF MAPK and PI3K PKB / AKT signal transduction cascades . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recombinant IGFBP 3 and IGFBP 4 were found to inhibit the IGF induced proliferation of an NIH3T3 cell line engineered to overexpress the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We evaluated the ex vivo expression of IGF 1 , VEGF , and their receptors ( IGF IR , Flt 1 , and KDR ) in human penile cavernosal smooth muscle cells ( HCSMCs ) to identify cellular and molecular pathways involved in the regulation of penile tissue vascularity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor regulates lifespan and resistance to oxidative stress in mice . ^^^ These results indicate that the IGF 1 receptor may be a central regulator of mammalian lifespan . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have investigated whether expression of IGF 1 , IGF 2 and insulin receptors ( IGF IR , IGF IIR and IR ; measured by real time RT PCR ) and binding capacity ( Bmax ) of IGF IR , IGF IIR and IR in the mucosa of the small and large intestine of neonatal calves are modified by age and different feeding regimes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RhoA and IGF I / IGF 1 receptor mRNA levels were determined by RT PCR and Northern blot . ^^^ IGF 1 mRNA was increased , but IGF 1 receptor mRNA was reduced in OVE 26 hearts and livers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : This study was conducted to detect the localization of the insulin like growth factor 1 receptor ( IGF 1 R ) in the cells and tissues in the rats with intrauterine growth retardation ( IUGR ) and normal growth rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In 3T3 L 1 cells , IGF 1 receptor is located in lipid rafts / caveolae of the plasma membrane and can directly interact with caveolin 1 , the major protein component in caveolae . ^^^ Disruption of lipid rafts / caveolae by depleting cellular cholesterol with cholesterol binding reagent , beta methylcyclodextrin or filipin , blocks the IGF 1 receptor signaling in 3T3 L 1 preadipocyte . ^^^ Further studies indicate that lipid rafts / caveolae are required only for IGF 1 receptor downstream signaling and not the activation of receptor itself by ligand . ^^^ Thus , our results suggest that localization in lipid rafts / caveolae and association with caveolin enable IGF 1 receptor to have a close contact with downstream signal molecules recruited into lipid rafts / caveolae and transmit the signal through these signal molecule complexes . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To define the specific role of IGF 1 receptor ( IGF IR ) in adipogenic and thermogenic differentiation of brown adipocytes during late fetal life , we have established immortalized brown adipocyte cell lines from fetuses of IGF IR deficient mice ( IGF IR ( / ) ) as well as from wild type mice ( IGF IR ( + / + ) ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition to the culture media of an IGF 1 receptor antagonist , the peptide JB 1 , did not affect the incorporation of bromodeoxiuridine to proliferating subependymal cells . ^^^ However , JB 1 significantly increased the number of TUNEL positive cells in the subependymal zone , suggesting that IGF 1 receptor is involved in the survival of subependymal neurons . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , only 5 . 3 % of hybrid embryos developed into blastocyst stage compared to 21 . 7 % in buffalo . mRNA phenotyping of insulin like growth factor family ( Insulin , insulin receptor , IGF 1 , IGF 1 receptor , IGF 2 , and IGF 2 receptor ) and glucose transporter isoforms ( GLUT 1 , 2 , 3 , 4 ) in hybrid embryos clearly showed that these molecules were not expressed after 8 cell stage onward . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , IGF 1 receptor ( IGF IR ) , IGF 2 , skeletal alpha actin ( sk actin ) , and beta myosin heavy chain ( beta MHC ) mRNAs were measured using Northern blot analysis and RT PCR . ^^^ IGF IR mRNA was significantly ( p < 0 . 05 ) increased after 6 weeks of training only in the IGF 1 treated animals . ^^^ Exogenous administration of IGF 1 , during the first week of the exercise session , did not produce any effect on myocardial IGF 1 but was associated with increased IGF IR signal after the long term exercise training . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This is congruent with a general theme of receptor signaling , where membrane G protein coupled receptors activate tyrosine kinase growth factor receptors ( EGFR , IGF 1 receptor ) that subsequently signal to MAPKs and other pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since many breast tumors and cancer cell lines overexpress IGF IR , we tested IGF 1 effects on chemotherapy treated breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF IR binding to its ligand , insulin like growth factor ( IGF 1 ) activates phosphoinositide 3 kinase ( PI3K ) , promotes cell proliferation by activating the mitogen activated protein kinase ( MAPK ) cascade , and blocks apoptosis by inducing the phosphorylation and inhibition of proapoptotic proteins such as BAD . ^^^ The simultaneous activation of MAP kinases and the inhibition of the stress activated arm of the cascade by IGF IR may constitute a potent proliferative signaling system and is possibly a mechanism by which IGF 1 can stimulate growth and inhibit cell death in a wide variety of cell types and biological settings . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The type 1 IGF receptor ( IGF1R ) mediates the effects of IGF 1 . ^^^ The antibody stimulated IGF1R activation in vitro in MCF 7 cells and was unable to block IGF 1 effects . ^^^ In contrast , IGF 1 treatment over the same time period did not affect IGF1R levels . ^^^ Our data show that scFv Fc stimulates biochemical activation of IGF1R , then causes receptor down regulation , making MCF 7 cells refractory to additional IGF 1 exposure . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Sequence dependence of C 5 propynyl dU , dC phosphorothioate oligonucleotide inhibition of the human IGF 1 receptor : mRNA , protein , and cell growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We previously reported evidence of a direct linkage between MycN and the IGF system in KP N RT human neuroblastoma cells , where IGF 1 induced both MycN expression at the RNA level and G 1 S cell cycle progression through the IGF 1 receptor ( IGF IR ) / MEK / mitogen activated protein kinase ( MAPK ) pathway ( A . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : To assess the effect of progesterone on the gene expression of insulin like growth factor 1 receptor ( IGF 1 R ) in human decidual stromal cells of early pregnancy in vitro . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
SPARC null mesangial cells produce increased amounts of IGF 1 and 2 , as well as IGF 1 receptor ( IGF 1R ) in comparison to wild type cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study was designed to investigate the roles of insulin like growth factor 1 ( IGF 1 ) , IGF type 1 receptor ( IGF IR ) and IGF binding proteins ( IGFBPs ) in regulating progesterone secretion by pig corpora lutea during the oestrous cycle , and the signal transduction pathways involved in mediating the steroidogenic actions of IGF 1 . ^^^ Neither anti IGF 1 nor anti IGF IR had significant effects on progesterone secretion , at any dose or day . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate whether TNF alpha deleteriously influences brain growth by altering the IGF 1 system in vivo , we examined the expression of IGF 1 , the type 1 IGF receptor ( IGF1R ) and IGF binding proteins ( IGFBPs ) in the brain of transgenic ( Tg ) mice with murine TNF alpha overexpression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expression of GH receptor , IGF 1 receptor , and IGF 1 mRNAs was confirmed . ^^^ GH increased IGF binding protein 3 ( IGFBP 3 ) , IGF 1 receptor protein and its phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Using semiquantitative reverse transcription polymerase chain reaction , we examined the expression of insulin like growth factor 1 ( Igf 1 ) , fibroblast growth factor 2 ( Fgf 2 ) , and their receptors ( Igf 1r , Fgfr 1 , Fgfr 2 , and Fgfr 3 ) in the MCC of 28 day old rats at 3 , 7 , and 14 days after placing intraoral appliances designed to produce a lateral functional shift of the mandible . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , immunoassays ignore the modifying effects of the IGF binding proteins ( IGFBPs ) on the interaction between IGF 1 and the IGF 1 receptor ( IGF IR ) . ^^^ Therefore , we developed an IGF 1 kinase receptor activation assay ( KIRA ) based on cells transfected with the human IGF IR gene . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , the distribution of IGF 1 , IGF type 1 receptor ( IGF IR ) , and IGF binding protein 2 ( IGFBP 2 ) was investigated during larval and post larval developmental stages of the shi drum ( Umbrina cirrosa ) by immunohistochemistry using antisera raised against Sparus aurata IGF 1 and IGF IR , and against mouse IGFBP 2 . ^^^ Immunoreactive IGFBP 2 , as detected by anti mouse IGFBP 2 antiserum , exhibited generally a similar distribution pattern to that of IGF 1 and IGF IR . ^^^ Localization of IGF 1 , IGF 1 receptor , and IGFBP 2 in developing Umbrina cirrosa ( Pisces : Osteichthyes ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Studies using alpha IR 3 antiserum which blocks ligand activation of IGF1R , showed that IGF1R participate in the autocrine or paracrine regulation of the number of cells in the inner cell mass by an endogenous IGF 1 IGF1R pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because both BDNF and IGF 1 are known to enhance neurite growth , but BDNF did not stimulate membrane expansion at the growth cone , we studied the effect of BDNF on the IGF 1 receptor . ^^^ BDNF was found to cause the translocation of the growth cone specific IGF 1 receptor subunit beta ( gc ) to the distal axon , in a KIF 2 dependent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
SUBJECTS AND METHODS : Five MSG tissue sections from SS and seven from mucocele patients were stained immunohistochemically using antibody to IGF 1 receptor and insulin receptor in a horse radish peroxidase and DAB system . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Protein levels of total and phosphorylated Akt and ERK1 / 2 , indicators of Akt and ERK1 / 2 activation , IGF 1 receptors ( pro IGF 1R and IGF 1Ralpha ) as well as the glucose transporter GLUT 4 were assessed by Western blot . ^^^ CONCLUSION : These results suggest that the cardiac IGF 1 resistance in diabetes is likely attributed , at least in part , to reduced IGF 1R and attenuated IGF 1 induced Akt phosphorylation under elevated extracellular glucose . . ^^^ The IGF 1 induced responses in NG or HG myocytes were blunted by the IGF 1 receptor antagonist H 1356 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 2 signalling is mediated through IGF 1 receptor ( IGF 1R ) , while mannose 6 phosphate / insulin like growth factor 2 receptor ( M6P / IGF 2R ) controls pericellular levels of free IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Production of ET 1 in EC was activated by insulin via the IGF 1 receptor , inasmuch as alphaIR ( 3 ) blocked insulin mediated upregulation of ET 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of recombinant human IGFBP 3 or antibodies against IGF 1 or IGF IR significantly inhibited proliferation of KF . ^^^ The bioavailability of IGF 1 may be related to the levels of IGFBP 3 produced , which in turn influences KF proliferation , suggesting that modulation of IGF 1 , IGF IR , and IGFBP 3 , individually or in combination , may represent novel approaches to the treatment of keloids . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The parietal endoderm was devoid of glucocorticoid receptor staining , whereas IGF 1 receptor was absent in visceral endoderm . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The abundance and expression levels of IGF 1 and IGF 1 receptor ( IGF 1 R ) were assessed also . ^^^ This was accompanied by a reduction in the expression of IGF 1 , IGF 1 receptor and PTH receptors . ^^^ PTH also up regulated its own receptor in control as well as during acidic conditions , and increased the expression levels of IGF 1 and IGF 1 receptor in the acidotic condyle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibition studies with IL 10 and IGF 1 receptor antibodies plus transfections experiments with IL 10 sense , and IGF 1 receptor antisense constructs confirmed these results . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This appeared to result from decreased proliferation in the Cap cells of the TEBs , a phenotype remarkably similar to that observed previously in IGF 1 receptor null mammary epithelium . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the other hand , IGF 1 receptor expression was increased at baseline in type 1 BB / Wor rats and decreased after crush injury , whereas its expression increased after crush injury in both control and type 2 BB / Z rats . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our data suggest that IRS 4 does not function as a substrate of the insulin and the IGF 1 receptor in primary muscle cells but may be involved in nonreceptor tyrosine kinase signaling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunoblotting demonstrated an increase in focal adhesion kinase and paxillin tyrosine phosphorylation followed by tyrosine phosphorylation of IGF 1 receptor in a time and dose dependent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) is known to stimulate collagen biosynthesis through interaction with IGF 1 receptor . ^^^ We investigated whether serum and tissue IGF 1 and IGF BPs as well as tissue IGF 1 receptor expression may reflect disturbances of collagen metabolism in patients with pancreatitis and pancreatic cancer . ^^^ In pancreatitis tissue , a significant increase in IGF 1 and IGFBP 3 content was accompanied by a distinct increase in IGF 1 receptor expression , compared to control pancreas tissue . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor mediates differentiation of primary cultures of mouse skeletal myoblasts . ^^^ However , when we interrupted IGF mediated signaling , by incubating myoblasts with suramin or with a monoclonal antibody to the IGF 1 receptor , differentiation was inhibited . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To elucidate the possible relationship between the insulin like growth factor ( IGF ) system and the development of different types of testis tumors in dogs , the expression of insulin like growth factor 1 and 2 ( IGF 1 and IGF 2 ) , their type 1 receptor ( IGF IR ) , and their binding proteins ( IGFBPs ) was examined . ^^^ In normal testes a clear expression of IGF 1 , IGF 2 , IGF IR , IGFBP 2 , IGFBP 4 and IGFBP 5 was found . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These findings suggest that estrogen effects in the brain may be mediated in part by the activation of the signaling pathways of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We demonstrate that the level of the mature form of the IGF 1 receptor is reduced and that IGF 1 dependent activation of p42 / p44 mitogen activated protein kinases ( MAPKs ) is compromised in preadipocytes with forced expression of Pref 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Basal levels of IGF 1 receptor ( IGF IR ) beta subunits , p 85 subunit of phosphatidylinositol 3 kinase , c Raf , phospho Raf 1 , phospho MEK 1 / 2 , phospho mitogen activated protein kinase , phospho Elk 1 and phospho Akt 1 were significantly reduced when KF cells were exposed to quercetin for 24 h . ^^^ Blocking IGF IR activity with IGF IR antibody or neutralizing endogenous IGF 1 activity with IGF 1 antibody led to significant growth inhibition suggesting the role of IGF 1 in regulation of KF proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : EtOH did not alter the total amount or tyrosine phosphorylation of the IGF 1 receptor , IRS 1 or PKB under basal or IGF stimulated conditions . ^^^ Furthermore , despite appropriate stimulation of IGF 1 receptor , IRS 1 and PKB , EtOH impairs IGF 1 signaling via S6K1 and 4E BP 1 pathways , and this defect is regulated in a glucocorticoid and TNF independent manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Systemic estradiol administration resulted in a transient immunocoprecipitation of the IGF 1 receptor with the estrogen receptor alpha and in a transient increase in tyrosine phosphorylation of the IGF 1 receptor in the hypothalamus of adult ovariectomized Wistar rats . ^^^ The interaction with the IGF 1 receptor was specific for the alpha form of the estrogen receptor and was also induced by intracerebroventricular injection of IGF 1 . ^^^ These hormonal actions may be part of the mechanism by which estradiol activates IGF 1 receptor signaling pathways in the brain and may explain the interdependence of estrogen receptors and the IGF 1 receptor in synaptic plasticity , neuroprotection and other neural events . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor ( IGF ) axis is a complex system composed of 2 mitogenic ligands , IGF 1 and 2 , 2 receptors , IGF 1R and IGF 2R , and 6 binding proteins , IGFBP 1 to 6 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Three cell surface proteins , alpha 5 beta 3 integrin , integrin associated protein , and SHPS 1 , have been shown to modulate both IGF 1 receptor linked signaling and cellular growth and migration responses that are stimulated by IGF 1 . ^^^ Ligand occupancy of these three proteins influences the recruitment of the phosphatase SHP 2 to the IGF 1 receptor and thereby modulates the duration of IGF 1 receptor tyrosine phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
States of hyperinsulinemia with insulin resistance are frequently associated with proliferative tissue abnormalities , via stimulation of DNA synthesis and cell proliferation through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Along with Ang 2 , we have previously shown that changes in IGF 1 receptor binding at myofibers are causative agents for cardiac eccentric hypertrophy . ^^^ This study investigated the interaction of the renin angiotensin system with the IGF 1 receptor during the development and regression of cardiac hypertrophy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor knockdown mice were fertile , slightly smaller and resisted oxidative stressors more effectively when compared with normal littermate mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The purpose of the current study was to localize the expression of IGF 1 and its receptor ( IGF IR ) mRNA and IGF IR protein in situ in the normal human eye and to examine the presence of expression in eyes with neovascular age related macular degeneration ( AMD ) . ^^^ IGF 1 and IGF IR mRNA was detected by in situ hybridization with digoxigenin labeled RNA probes . ^^^ RESULTS : In the normal retina , IGF 1 and IGF IR mRNA expression was found throughout the neuroretinal layers , in the retinal pigment epithelium ( RPE ) , and in some choriocapillary and retinal capillary endothelial cells . ^^^ Because IGF 1 participates in ocular neovascularization , synthesis of IGF IR and IGF 1 in endothelial cells , RPE cells , and fibroblast like cells in CNV may point toward a role for this growth factor in the pathogenesis of neovascular AMD . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and binding protein 5 mRNA expression was induced throughout the 15 day period of SI , whereas IGF 1 mRNA was induced at 8 and 15 days . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This response required the IGF 1 receptor , which activates phosphoinositide 3 kinase ( PI3K ) and mitogen activated protein kinase / extracellular signal regulated kinase ( MAPK / ERK ) pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OP 1 was found to enhance mRNA levels of IGF 1 and the IGF 1 receptor , the latter of which appeared to be responsible for the combined effect of IGF 1 and OP 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 , long R ( 3 ) IGF 1 ( only binds IGF 1 receptor ) , AL ( 31 ) Leu ( 60 ) IGF 1 ( only binds IGFBPs ) , antihuman IGF 1 receptor antibodies , and IGFBP 1 were then added to LNCaP cultures to determine the independent effects of IGF 1 and IGFBP 1 on cell growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The CILP 1 N terminal domain also suppressed IGF 1 induced ( but not TGFbeta induced ) proliferation and sulfated proteoglycan synthesis , and it inhibited ligand induced IGF 1 receptor autophosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Captopril reduced blood pressure , attenuated cardiac remodeling , and caused a threefold increase in IGF 1 receptor mRNA and protein in infarct , border zone , and viable myocardium ( p < 0 . 01 ) . ^^^ These data suggest that the benefits of ACE inhibitors in attenuation of cardiac remodeling may be mediated in part through increased expression of the IGF 1 receptor sensitizing the myocardium to the positive effects of endogenous IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor is commonly ( though not always ) overexpressed in many cancers , and many recent studies have identified new signaling pathways emanating from the IGF 1 receptor that affect cancer cell proliferation , adhesion , migration and cell death ; functions that are critical for cancer cell survival and metastases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
With respect to the gene expression of other IGF system components , VA deficiency caused a twofold induction of IGF 1 receptor ( IGF IR ) mRNA in the heart and a twofold reduction in IGFBP 6 mRNA in the lungs , but did not alter the expression of IGF 2 , IGFBP 1 , IGFBP 3 , IGFBP 4 or IGFBP 5 in all tissues examined . ^^^ When VA deficient rats received a single injection of retinoic acid ( 2 mg / rat ) , tissue IGF 1 and IGF IR gene expression did not change after 4 or 8 h , while the expression of IGF 2 , IGFBP 4 , and IGFBP 6 mRNAs in some tissues increased rapidly . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The aim of the present study was to investigate the intracellular mediators of the third base mutant of codon 249 in p 53 gene ( p53mt249 ) mutation that potentiate IGF 2 dependent IGF 1 receptor ( IGF IR ) signaling . p53mt249 enhanced IGF 2 dependent IGF IR signaling in p 53 negative Hep3B hepatoma cells which were specifically prevented by IGF IR antibody , alpha IR 3 and lovastin . p53mt249 increased the number of IGF 2 binding sites with no change in the affinity of IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These defects are strikingly similar to the phenotypes of IGF 1 receptor deficient mice and suggest that Akt may serve as the most critical downstream effector of the IGF 1 receptor during development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ligand occupancy of the alphaVbeta 3 integrin is required for IGF 1 receptor ( IGF IR ) phosphorylation of an appropriate duration and for stimulation of IGF 1 actions . ^^^ When IGF 1 was added to cells expressing mutant beta 3 , SHP 2 was not recruited to the Src homology 2 domain containing tyrosine phosphatase substrate 1 or to IGF IR . ^^^ This was associated with prolonged IGF IR phosphorylation and an impaired cellular DNA synthesis response to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and the IGF IR specific IGF 1 analog , des ( 1 3 ) , mimic the effects of GD IgG . ^^^ Moreover , GD IgG displaces specific ( 125 ) 1 labeled IGF 1 binding to fibroblasts and attenuates IGF IR detection by flow cytometry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mouse NIH 3T3 fibroblasts expressing either the wild type human IGF 1R or IR were stimulated with either IGF 1 or insulin , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
AIM : To study the expression of IGF 1 and IGF 1R and its intervention by interleukin 10 in the course of experimental hepatic fibrosis . ^^^ Immunoreactivities for insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF 1R ) were demonstrated by immunohistochemistry , and their intensities were evaluated in different animal groups . ^^^ RESULTS : The positive levels for IGF 1 and IGF 1R were increased with the development of hepatic fibrosis , with the positive signals localized in cytoplasm and / or at the plasmic membrane of hepatocytes . ^^^ The positive signals of IGF 1 and IGF 1R were observed more frequently ( P < 0 . 01 ) in the CCl 4 treated group ( 92 . 0 % and 90 . 0 % ) compared to those in the control group . ^^^ The responses in IGF 1 and IGF 1R expression correlated with the time of IL 10 treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dietary administration of corticosterone also reduced plasma insulin like growth factor 1 ( IGF 1 ) and levels of IGF 1 receptor in mammary carcinomas ( P < 0 . 01 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and PDGF R beta levels were higher in neointimal cells than in medial cells , but the FGF receptor level was not different between the cell types . ^^^ In summary , our results indicate that neointimal cells are more sensitive to growth factors than medial cells , likely due to a higher expression of IGF 1 receptor and PDGF R beta . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here we provide evidence that TNFalpha acts on muscle cells to induce a state of IGF 1 receptor resistance . ^^^ These data are consistent with the notion that very low physiological concentrations of TNFalpha interfere with both protein synthesis and muscle cell development by inducing a state of IGF 1 receptor resistance . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To precisely define the role of insulin and IGF 1 signaling in endothelium in these processes , we have used the oxygen induced retinopathy model to study mice with a vascular endothelial cell specific knockout of the insulin receptor ( VENIRKO ) or IGF 1 receptor ( VENIFARKO ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Dominant negative muscle specific IGF 1 receptor ( MKR ) mice exhibit elevated lipid levels at an early age and eventually develop type 2 diabetes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the quadriceps muscle , the expression of IGF 1 , IGF 1 receptor , IL 1beta and TNFalpha were assessed by RT PCR and quantitative immunohistochemistry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , TGF beta 1 decreased the IGF 1 induced tyrosine phosphorylation of the adaptor protein CrkII and its association with the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Genistein , biochanin A , quercetin and kaempferol reduced the insulin receptor substrate 1 ( IRS 1 ) content of AT6 . 3 cells and prevented the down regulation of IGF 1 receptor beta in response to IGF 1 binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this paper we tested the hypothesis that polymorphic variants of IGF 1 response pathway genes , namely IGF IR ( IGF 1 receptor ; G / A , codon 1013 ) , PI3KCB ( phosphoinositol 3 kinase ; T / C , 359 bp ; A / G , 303 bp ) , IRS 1 ( insulin receptor substrate 1 ; G / A , codon 972 ) , and FOXO1A ( T / C , +97347 bp ) , play a role in systemic IGF 1 regulation and human longevity . ^^^ The major finding of this investigation was that subjects carrying at least an A allele at IGF IR have low levels of free plasma IGF 1 and are more represented among long lived people . ^^^ Moreover , genotype combinations at IGF IR and PI3KCB genes affect free IGF 1 plasma levels and longevity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1R , IGF 1 and IGF 2 expression as potential prognostic and predictive markers in colorectal cancer . ^^^ Insulin like growth factors ( IGF 1 and IGF 2 ) and the IGF 1 membrane receptor ( IGF 1R ) have been found to play a critical role in the carcinogenesis of several tumors , among them colorectal cancer ( CRC ) . ^^^ To study the prognostic impact of these molecules , a total number of 713 cases of CRC were examined for the expression of IGF 1 , IGF 2 , and IGF 1R . ^^^ IGF 1 expression was noted in 53 ( 7 . 5 % ) , IGF 2 in 88 ( 12 . 6 % ) , and IGF 1R in 698 ( 99 . 6 % ) of the cases . ^^^ Although the synchronous expression of IGF 1 , IGF 2 , and IGF 1R in a subset of CRC is consistent with an auto / paracrine loop of cancer cell autostimulation , the prognostic effect of IGF 1 and IGF 2 expression seems to be of limited value . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This IGF 1 effect was reduced by 50 % in MCF 7 derived cells ( SX 13 ) , which exhibit a 50 % reduction in IGF 1R expression , demonstrating that IGF 1 receptor activation was involved in this process . ^^^ To study the role of IGF 1 receptor signaling on cell cycle events we utilized MCF 7 breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
AG 538 is a substrate competitive inhibitor of the IGF 1 receptor ( IGF 1R ) , with an IC 50 = 61 nM in a cell free kinase assay ( Blum , G . , Gazit , A . , and Levitzki , A . ( 2000 ) Biochemistry 39 , 15705 15712 ) . ^^^ IGF 1 induced IGF 1R autophosphorylation ; IRS 1 phosphorylation and protein kinase B activation are inhibited at a low micromolar concentration range when applied to intact cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We demonstrate that direct contact between 5TMM cells and BM endothelium up regulates the expression of chemoattractant receptors and adhesion molecules such as IGF 1 receptor and CD44v6 , which confer homing to the MM cells to the BM and enhance their adhesion to BM stroma . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
DHT and 1 , 25 ( OH ) 2D3 increased messenger RNAs ( mRNAs ) of their cognate receptors and of IGF 1 receptor mRNA ( IGF 1 R ) . 1 , 25 ( OH ) 2D3 also stimulated mRNA of the androgen receptor ( AR ) , whereas DHT did not affect mRNA of the vitamin D receptor ( VDR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blood and skeletal muscle were collected and IGF 1 receptor , Akt 1 and p 70 S6K protein contents and their phosphorylation status were determined . ^^^ Total IGF 1 receptor protein and IGF 1 receptor phosphorylation were lower in aged mice ( P < 0 . 05 ) . ^^^ It is concluded that there was an aging related resistance at the p 70 S6K level in mouse skeletal muscle that could not be restored by prior exercise and this resistance is associated with lower IGF 1 receptor number and Akt 1 phosphorylation in the aged skeletal muscle . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Reverse transcriptase polymerase chain reaction and Western blot analysis of total cell lysates revealed that CLA decreased IGF 1 receptor ( IGF IR ) transcript and protein levels in a dose dependent manner . ^^^ Immunoprecipitation / Western blot studies revealed that CLA inhibited IGF 1 induced phosphorylation of IGF IR and insulin receptor substrate ( IRS ) 1 , recruitment of the p 85 regulatory subunit of phosphatidylinositol 3 kinase ( PI3K ) to IGF IR , IGF IR associated PI3K activity , and phosphorylated Akt and extracellular signal regulated kinase ( ERK ) 1 / 2 levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Sixty seven breast surgical specimens from women with and without diabetes who did not have cancer and from women with and without diabetes who did have cancer were studied for insulin like growth factor 1 ( IGF 1 ) , the IGF 1 receptor ( IGF IR ) , insulin like growth factor binding protein 3 ( IGFBP 3 ) , and oestrogen receptor 1 gene expression . ^^^ RESULTS : The expression of IGF 1 and IGF IR was significantly lower in the cancer groups , whereas there was no significant difference for IGFBP 3 between women with and without cancer . ^^^ Moreover , there was a good correlation between the expression of IGF 1 and IGF IR in women without cancer : this link was still present in breast tissue from patients with diabetes and cancer , whereas it was lost in patients without diabetes but with cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In a further series of experiments we demonstrate that IGF 1 is able to replace insulin in the DIP lactogenic hormone mix and by the use of a specific IGF 1 receptor blocking antibody indicate that the action of IGF 1 is mediated through the cell surface IGF 1 receptor and not by cross reaction of IGF 1 ligand at the insulin receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Further analysis revealed that the majority of BMSC expressed the alpha and beta subunits of the type 1 receptor for IGF 1 ( IGF IR ) , in the expected 1 : 1 ratio . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , analogues of IGF 2 [ leu 27 IGF 2 and Des ( 1 6 ) IGF 2 ] , with altered affinities for the IGF 1 receptor and IGF binding proteins ( IGFBPs ) , but retained affinities for the IGF 2 receptor , also completely inhibited ( 100 % ; P < 0 . 01 ) RA induced apoptosis , while an IGF 1 receptor antagonist did not reduce the survival effects of IGF 2 . ^^^ The inhibition of RA action by IGF 2 was independent of its ability to signal through the IGF 1 receptor or to interact with IGFBPs . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , IGF IR and GHR mRNA expression were significantly increased by the lack of dietary protein , whereas the levels of IGF 1 mRNA remained unchanged . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Intracerebroventricular infusions of a selective IGF 1 receptor antagonist were administered to ovariectomized rats every 12 h beginning 1 h before the first of two daily E ( 2 ) injections . ^^^ IGF 1 receptor blockade partially inhibits lordosis if the antagonist is infused throughout the 2 d estrogen treatment period but not if it is administered only during the first or last 12 h of estrogen treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This was due to proteolysis of the insulin like growth factor ( IGF ) binding protein 3 by MMP 19 , which augmented signaling through the IGF 1 receptor , as evidenced by its increased autophosphorylation . ^^^
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IGF 1R Rz 1 also reduced IGF 1 induced cell migration by 90 % + / 5 % ( P = 2 . 9 10 10 ( 9 ) ) showing that IGF 1R Rz 1 reduces IGF 1R function in HRECs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Stimulation of IGF 1 receptor coupled with tyrosine kinase activates phosphatidylinositol 3 kinase and subsequently , protein kinase B ( Akt ) in hippocampal neurons . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to gain further insight into IGF 1 receptor signaling in Xenopus laevis oocytes and embryos , we have undertaken the characterization of the adapter protein Shc and studied its implication in oocyte maturation induced after IGF 1 receptor activation , especially since expression of this molecule has been indirectly evidenced in Xenopus oocytes , eggs and embryos . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
EM 164 was initially selected by a rapid cell based screen of hybridoma supernatants to identify antibodies that bind to IGF IR but not to the homologous insulin receptor and that show maximal inhibition of IGF 1 stimulated autophosphorylation of IGF IR . ^^^ EM 164 binds tightly to IGF IR with a dissociation constant K ( d ) of 0 . 1 nM , inhibits binding of IGF 1 and antagonizes its effects on cells completely , and has no agonistic activity on its own . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In these cells , IGF 2 gene and protein expression are induced as early events in differentiation , and the IGF 1 receptor and downstream signaling molecules , including Akt , are rapidly activated . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We fused the cytoplasmic domain of the IGF 1R to the extracellular and transmembrane domains of the oncogenic ErbB 2 receptor ( ErbB 2 ( 5 > E ) / IGF 1 ) . ^^^ Crosstalk between the extracellular domain of the ErbB 2 receptor and IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 stimulates the IGF 1 receptor ( IGF1R ) and downstream signaling pathways , including extracellular signal regulated kinase ( ERK ) and phosphoinositol 3 kinase ( PI3K ) . ^^^ We conclude that 1 ) IGF 1 through IGF1R stimulates cardiomyocyte division in vivo ; hyperplastic growth is the most likely explanation of IGF 1 stimulated heart growth in vivo ; 2 ) IGF 1 through IGF1R does not stimulate binucleation in vitro or in vivo ; 3 ) IGF 1 through IGF1R does not stimulate hypertrophy either in vivo or in vitro ; and 4 ) IGF 1 through IGF1R requires both ERK and PI3K signaling for proliferation of near term fetal sheep cardiomyocytes in vitro . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that there are interactions between the various pathways down stream of the IGF 1 receptor that may behave differently in vivo than in myogenic cell lines in vitro . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF IR ) localizes in caveolae and tyrosine phosphorylates caveolin 1 , supporting a role for these subcellular regions in the compartmentalization of IGF 1 signaling . ^^^ Src homology 2 / alpha collagen related protein ( Shc ) is the main mediator of IGF 1 mitogenic action , coupling IGF IR phosphorylation to Ras MAPK activation . ^^^ Finally , we have observed that after IGF 1 stimulation , IGF IR and Fyn colocalize in lipid raft caveolin 1 enriched microdomains . ^^^ Our results suggest that 1 ) IGF 1 causes the colocalization of signaling proteins in caveolae through a phosphorylation regulated mechanism ; and 2 ) the time course of phosphorylation and recruitment of substrates in caveolae by insulin receptor and IGF IR could determine the specific actions of these receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 stimulates cell division in numerous cell types after activation of the IGF 1 receptor , a transmembrane heterotetramer linked to the ras raf MAPK and phosphatidylinositol 3 kinase signaling pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Possible involvement of IGF 1 receptor and IGF binding protein in insulin induced enhancement of noradrenaline response in diabetic rat aorta . 1 . ^^^ The expressions of the IGF 1 receptor mRNA and protein were increased in STZ induced diabetic aortas and further increased in insulin treated diabetics . ^^^ These results suggest that the insulin deficiency and chronic hyperinsulinemia in diabetes upregulate the IGF 1 receptor and downregulate IGFBP 4 and IGFBP 5 in the aorta . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Compared with the cells transduced with a control vector , overexpression of Hsp 10 or Hsp 60 increased the abundance of IGF 1R and IGF 1 stimulated receptor autophosphorylation . ^^^ Transducing cardiomyocytes with antisense Hsp 60 oligonucleotides reduced Hsp 60 expression , decreased the abundance of IGF 1R , attenuated IGF 1R autophosphorylation , and suppressed the pro survival action of IGF 1 in cardiomyocytes . ^^^ Additional experiments showed that Hsp 10 and Hsp 60 suppressed polyubiquitination of IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Subsequently , SHP 2 is transferred to IGF 1 receptor and regulates the duration of IGF 1 receptor phosphorylation . ^^^ This was associated with a lack of SHP 2 transfer to IGF 1 receptor and sustained receptor phosphorylation . ^^^
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In terms of IGF 1 related second messenger proteins , the effect of thapsigargin is specific for IRS 1 since the protein levels of IGF 1 receptor beta subunit , Akt , Erk , and Shc are not affected . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The transcript level of upstream signaling molecules , such as IGF binding protein 5 ( IGFBP 5 ) , IGF 1 receptor ( IGF 1R ) , and phosphoinositide 3 kinase ( PI3K ) , was studied using reverse transcription polymerase chain reaction ( RT PCR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cells with increased M6P / IGF IIR expression exhibited reduced phosphorylation of IGF 1 receptor and p44 / 42 MAPK compared to vector transfectants , or wild type MDA MB 231 cells . ^^^ These results therefore suggest that M6P / IGF IIR levels can modulate breast cancer cell tumorigenicity by a mechanism that may involve altered IGF 1 receptor signaling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 increases adhesion of MM . 1S and OPM 6 MM cells to fibronectin ( FN ) in a time and dose dependent manner , as a consequence of IGF IR activation . ^^^ IGF 1 rapidly and transiently induces association of IGF IR and beta 1 integrin , with phosphorylation of IGF IR , IRS 1 , and p 85 ( PI 3 K ) . ^^^ Both IGF IR and beta 1 integrin colocalize to lipid rafts on the plasma membrane after IGF 1 stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Remarkably , this pathway is insensitive to chemical inhibition of IGF 1 receptor tyrosine kinase activity . ^^^ These results suggest that , in addition to their roles in G protein coupled receptor signaling , beta arrestins couple the IGF 1 receptor tyrosine kinase to the phosphatidylinositol 3 kinase system and suggest that this mechanism is operative independently of the tyrosine kinase activity of the receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that insulin receptor substrate 2 ( IRS 2 ) levels were markedly induced by progesterone and the synthetic progestin R 5020 in MCF 7 and other progesterone receptor ( PR ) positive breast cancer cell lines , whereas IRS 1 and the IGF 1 receptor were not induced . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Pretreatment with fibroblast growth factor 2 ( FGF 2 ) increased the IGF 1 receptor ( IGF IR ) expression , and both FGF 2 and IGF 1 were required for maximal proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
OBJECTIVE : We have shown previously that oxidized LDL decreases insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor expression in vascular smooth muscle cells and that IGF 1 and IGF 1 receptor expression are reduced in the deep intima of early atherosclerotic lesions . ^^^ Overexpression of the IGF 1 receptor by using an adenovirus completely abrogated these effects . ^^^ The antiapoptotic function of the IGF 1 receptor was associated with increased Akt kinase activity and increased expression of phosphorylated Bad . ^^^ Moreover , a dominant negative p 85 phosphatidylinositol 3 kinase adenovirus blocked the capacity of the IGF 1 receptor to prevent oxidized LDL induced apoptosis . ^^^ CONCLUSIONS : Our data demonstrate that IGF 1 receptor activation inhibits oxidized LDL induced cytochrome C release and apoptosis through the phosphatidylinositol 3 kinase / Akt signaling pathway and suggest that genetic or pharmacological activation of the IGF 1 receptor may be a useful strategy to stabilize atherosclerotic plaques . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The angiogenic response of IGF 2 could be reversed by the addition of beta galactosidase or rabbit antihuman IGF II / M6P receptor antiserum , whereas blocking antibodies against IGF 1 receptor or insulin receptor influenced IGF 2 induced sprout formation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Truncated IGF 1 receptors ( IGF Ir / dn ; 482 and 950 amino acids long , respectively , IGF Ir / 482st and IGF Ir / 950st ) that function as dominant negative inhibitor were cloned into recombinant adenoviruses and used to treat human pancreatic cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the absence of IGF 1 stimulation , or if mutated IGF IR fails to phosphorylate IRS 1 , localization of Rad 51 to the sites of damaged DNA is diminished . ^^^
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The response of smooth muscle cells to IGF 1 is determined not only by activation of the IGF 1 receptor but also by at least three other transmembrane proteins , alphaVbeta 3 , integrin associated protein ( IAP ) , and SHPS 1 . ^^^ This delay in SHP 2 transfer seems to account for the increase in the duration of IGF 1 receptor phosphorylation and for enhanced downstream signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , Zn ( 2+ ) increases the affinity by which either [ ( 125 ) 1 ] IGF 1 or [ ( 125 ) 1 ] R ( 3 ) IGF 1 binds to the IGF 1R , but depresses [ ( 125 ) 1 ] IGF 2 binding to the IGF type 2 receptor ( IGF 2R ) on BC ( 3 ) H 1 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It has been found that Mel pro is more effectively transported into the MDA MB 231 cells , evokes higher cytotoxicity , similar inhibitory effect on DNA synthesis , lower inhibitory effect on collagen biosynthesis and reduces IGF 1 receptor and MAPkinase expression in MDA MB 231 cells , compared to Mel . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Estrogens increase the effect of IGF 1 on breast cancer cells by stimulating the expression of IGF 1 and IGF 1 receptor ; IGFs enhance the action of estrogens by regulating the production of estrogen receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The developmental patterns of GH R , IGF 1 and IGF IR gene expression in adipose tissue of Erhualian and large white pigs ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the other hand , an inducible isoform of COX ( COX 2 ) , insulin like growth factor ( IGF ) 2 , and IGF 1 receptor ( IGF IR ) are up regulated in colon carcinoma and might have crucial roles in tumor growth and invasion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockade of the IGF 1 receptor ( IGF IR ) with an IGF IR antibody decreased the stimulatory influence of IGF 1 on Sp 1 protein levels and PYY ( 127 / +37 bp ) luc activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
ZD 1839 had no effect on IGF 1 receptor ( IGF IR ) autophosphorylation in intact cells . ^^^ These findings indicate that IGF 1 utilizes a novel EGFR dependent signaling pathway involving the formation of a complex between the IGF IR and the EGFR to activate the ERK pathway and to stimulate proliferation in normal human mammary epithelial cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To study mechanisms of IGF action in muscle , we have developed a mouse myoblast cell line termed C2BP5 that is dependent on activation of the IGF 1 receptor and the phosphatidyl inositol 3 kinase ( PI 3 kinase ) Akt pathway for initiation of differentiation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The aim of the current study was to examine the role of IGF 1 in cardiac myocytes in the absence of secondary effects , and to elucidate downstream signaling pathways and transcriptional regulatory effects of the IGF 1 receptor ( IGF1R ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : Treatment with IGF BP 3 significantly reduced the levels ( mean intensity per pixel ) of EGF R , IGF 2 , and VEGF in all three cell lines and IGF 1 receptor ( IGF IR ) in representative ME 180 cell line . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Infusions of WDS or BTS after a fertile AI did not affect IGF 1 , IGF 1 receptor , or IGF 2 mRNA levels compared with gilts infused with BTS only , whereas the mRNA abundance for the IGF 2 receptor was decreased ( P < 0 . 05 ) in WDS infused gilts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 induced up regulation of VEGF production was associated with activation of AP 1 and HIF 1 alpha and was abrogated by phosphatidylinositol 3 kinase inhibitors ( wortmannin and LY 294002 ) ; Jun kinase inhibitor ( SP 600125 ) ; HIF 1 alpha antisense oligonucleotide ; or geldanamycin , an inhibitor of the heat shock protein 90 molecular chaperone , which regulates the three dimensional conformation and function of IGF 1 receptor and Akt . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The truncated receptor in the LCC 6 DN cells behaved in a dominant negative manner to inhibit endogenous IGF1R activation by IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The animals were killed 11 weeks after the DMBA application , and the levels of IGF 1 , IGF 1 receptor ( IGF IR ) , Akt , Bcl 2 and Bad in tumorous and nontumorous breast tissue samples were measured by Western blot analysis . ^^^ RESULTS : GLN supplementation resulted in a significant decrease in the levels of IGF 1 , IGF IR , Akt , and Bcl 2 in nontumorous samples . ^^^ The samples collected from tumor tissues showed lower levels of IGF 1 , Akt , Bcl 2 , Bad , and IGF IR in comparison with nontumorous tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Colon cancer overexpresses insulin like growth factor 1 ( IGF 1 ) and insulin like growth factor 1 receptor ( IGF 1 R ) , as compared with normal or adenomatous mucosa , and it has been postulated that colorectal cancer cells depend on the IGF1 / IGF1 R pathway for their growth and progression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The metabolic and mitogenic actions of insulin and insulin like growth factor ( IGF ) 1 and 2 are thought to be mediated mainly by the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor immunoreactive astrocytes were detected in the spinal cord , brainstem , central gray and cerebellar nuclei of SOD 1 ( G93A ) transgenic mice . ^^^ In contrast to transgenic mice , no IGF 1 receptor immunoreactive astrocytes were observed in any brain region of wtSOD 1 transgenic mice although a few moderately stained neurons were observed . ^^^ In the hippocampal formation of SOD 1 ( G93A ) transgenic mice , IGF 1 receptor immunoreactivity was increased in the pyramidal cells of the CA 1 3 regions and granule cells of the dentate gyrus . ^^^ The present study provides the first evidence that IGF 1 receptor immunoreactivity was increased in reactive astrocytes in the central nervous system of SOD ( G93A ) transgenic mice , suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS . ^^^ The mechanisms underlying the increased immunoreactivity for IGF 1 receptor , and the functional implications of these increases , require elucidation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The presence of gold particles over the plasma membrane is an indication that IGF 1 receptor is a membrane bound receptor . ^^^ Furthermore , the intracellular distribution of the label over the endoplasmic reticulum supports the local synthesis of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We used SKBR3 / neo cells ( expressing few IGF 1 receptors ) and SKBR3 / IGF IR cells ( overexpressing IGF 1 receptor ) as our experimental model . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we analyzed the contribution of the 2 major pathways of the intracellular IGF IR signaling cascade to the overall effects elicited by IGF 1 in ES . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
It consists of IGF 1 , IGF 2 , insulin , IGF 1 receptor , and those of IGF 2 and insulin as well as IGF binding proteins . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Extensive data are available on the importance of the insulin like growth factor ( IGF ) system in growth regulation of breast cancer cell lines in vitro , indicating that the IGF 1 receptor ( IGF IR ) , IGF 1 ( and IGF 2 ) function as survival factors , while IGF binding protein ( IGFBP ) 3 may act as a growth inhibitor . ^^^ In vivo studies indicate a role of IGF 1 and IGF IR in breast cancer development . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 binds to the IGF 1 receptor , a tyrosine kinase receptor that transduces signals to the nucleus and mitochondrion primarily via the mitogen activated protein kinase ( MAPK ) and PI3K / Akt pathways . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockage of IGF 1 receptors by intracerebroventricular JB 1 , an IGF 1 receptor antagonist , attenuated both estrogen and IGF 1 neuroprotection of nigrostriatal DA neurons and motor behavior . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The hallmark molecular profile of MM cells before their commitment to SAHA induced cell death is a constellation of antiproliferative and / or proapoptotic molecular events , including down regulation of transcripts for members of the insulin like growth factor ( IGF ) / IGF 1 receptor ( IGF 1R ) and IL 6 receptor ( IL 6R ) signaling cascades , antiapoptotic molecules ( e . g . , caspase inhibitors ) , oncogenic kinases , DNA synthesis / repair enzymes , and transcription factors ( e . g . , XBP 1 , E2F 1 ) implicated in MM pathophysiology . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In SKBR3 / IGF IR cells , reduction of ErbB 2 by antisense methodology restores the IGF 1 induced MAPK activation . ^^^ They are consistent with the view that the IGF IR mediated attenuation of trastuzumab induced growth inhibition we recently described is dependent on IGF 1 induced PI3K signaling rather than IGF 1 induced MAPK signaling . . ^^^ However , IGF 1 induced tyrosine phosphorylation of IGF 1 receptor and IRS 1 and AKT phosphorylation were unaffected by ErbB 2 overexpression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Interestingly , EphA 3 expression in CD 28 stimulated Jurkat cells was enhanced by IGF 1 or by overexpression of the IGF 1R , and was suppressed by anti IGF 1R blocking antibodies . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Glutamate induces loss of sensitivity to IGF 1 by phosphorylating the IGF 1 receptor docking protein insulin receptor substrate ( IRS ) 1 in Ser ( 307 ) through a pathway involving activation of PKA and PKC in a hierarchical fashion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since 1996 , seven genetic mouse models have been reported to show increased lifespan : Ames and Snell dwarf mice , the ' little mouse ' ( Ghrhr ( lit / lit ) ) , mice null for either growth hormone receptor / binding protein ( GHR / BP ( / ) ) or p 66 ( shc ) ( p 66 ( shc / ) ) , mice heterozygous for the IGF 1 receptor ( Igf1r ( + / ) ) , and fat specific insulin receptor knockout mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Multiple signaling pathways are involved in the regulation of IGF 1 receptor inhibition of PTEN enhanced apoptosis . ^^^ Furthermore , IGF 1 receptor abrogation of this apoptotic effect was inhibited by both PI 3 ' kinase and by specific inhibitors of p 38 MAP kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , the plasma IGF 1 concentration was about twofold higher in the HL group ( P < 0 . 05 ) , and the maximal rumen epithelial IGF 1R binding was also higher in the HL ( P < 0 . 05 ) than in the LL group . ^^^ IGF 1R mRNA and IGF 1 mRNA were detected in rumen papillae ; however , they were unaffected by dietary treatments . ^^^ Thus dietary energy dependent alterations of rumen morphology and function are accompanied by corresponding changes in systemic IGF 1 and ruminal IGF 1R . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These expression patterns are very similar to those of the IGF 1 receptor and suggest that Dok 1 could be among the downstream targets of IGF signaling in areas of the primate brain involved in learning and memory . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A plasmid construct containing a mutant IGF 1 receptor ( IGF IR DN ) fused to the tetracycline operator ( tetOPh ( CMV ) IGF IR DN ) was stably transfected into MCF 7 human breast cancer cells . ^^^ Interestingly , autophosphorylation of the IGF IR and phosphorylation of the downstream substrate , insulin receptor substrate 1 ( IRS 1 ) , was not inhibited in doxycycline / IGF 1 treated cells , suggesting the possibility that activation of downstream substrates other than the IRS 1 may be critical for optimal cell proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Rapid induction of IGF IR signaling in normal and tumor tissue following intravenous injection of IGF 1 in mice . ^^^ Tail vein 4 injection of IGF 1 into mice resulted in a rapid and dose dependent activation of the IGF 1 receptor and downstream phosphorylation of Akt and ERK1 / 2 in liver , kidney , and mammary gland . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF IR ) has emerged as a good therapeutic site for ES patients . ^^^ Taken together , these findings add a new activity to the IGF 1 repertoire in ES and highlight how disruption of IGF IR functions may constitute an effective tool for the control of neovascularization in this tumor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Characteristic alterations detected in HCC and hepatoma cell lines comprise the overexpression of IGF 2 and the IGF 1 receptor emerging as critical events in malignant transformation and growth of tumors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Emerging evidence suggests that members of the Insulin like Growth Factors ( IGFs ) family , including IGF 1 , IGF 2 , the IGF 1 receptor ( IGF IR ) , and the IGF binding proteins ( IGFBPs ) play a central role in the development and progression of cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
MG 63 osteosarcoma cells were treated with serum free medium alone or in combination with IGF 1 , a neutralizing antibody against the human IGF 1 receptor ( alphaIR 3 ) or non immune control IgG ( 1 ) for two to six days . ^^^ We investigated cell survival ( cell count ) , proliferation ( CD 71 FACS ) , apoptosis ( Annexin 5 FACS , Caspase 3 activity , PCD ) and anti apoptosis ( 112 Ser Bad phosphorylation ) , and regulation of IGF 1 receptor surface expression ( IGF 1 receptor FACS ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Proliferative and anti apoptotic actions of IGFs are mediated by the IGF 1 receptor ( IGF IR ) , to which both IGF 1 and 2 bind with high affinity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report that more tumorigenic and motile N cells express higher levels of IGF 1 receptor ( IGF IR ) than less tumorigenic , more adherent S cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effects of recombinant bovine somatotropin ( rbST ) on tissue IGF 1 , IGF 1 receptor , and GH mRNA levels in rainbow trout , Oncorhynchus mykiss . ^^^ Therefore an experiment was conducted to examine the effects of rbST treatment on tissue GH , IGF 1 , and IGF 1 receptor A ( rA ) expression in rainbow trout . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , estrogen administration completely suppressed IGF 1 mRNA ( P=0 . 004 ) and protein but had no effect on IGF 1R . ^^^ Estradiol treatment reduced immunoreactivity of IGF 1 , PDGF A , PDGF Ralpha , and PDGF B in vascular lesions , whereas no changes were seen with respect to IGF 1R and PDGF Rbeta . ^^^ CONCLUSIONS : Our findings demonstrate that estrogen regulates IGF 1 , PDGF A , PDGF B , and PDGF Ralpha , which may be related to the vasculoprotective effect of estrogen , but has no effect on IGF 1R or PDGF Rbeta . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cytokine dependent FDC P 1 hematopoietic cells were conditionally transformed to grow in response to overexpression of IGF 1R in the presence of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Possible involvement of IGF 1 receptor and IGF binding protein in insulin induced enhancement of noradrenaline response in diabetic rat aorta ] . ^^^ Furthermore , the expression of the IGF 1 receptor was higher in the aorta in insulin treated diabetic than in untreated diabetes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF 1R ) expression in human lung in RDS and BPD . ^^^ We hypothesize that IGF 1 and IGF 1R proteins are upregulated in lung epithelia and fibroblasts in RDS compared to normal development , and are further upregulated in BPD . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Addition of IGFBP 3 inhibited IGF 1 mediated IGF type 1 receptor ( IGF IR ) phosphorylation and activation of the downstream molecule Akt in BALB / c 3T3 fibroblasts overexpressing human IGF IR ( 3T3 IGF IR ) and in two human colon cancer cell lines ( COLO 201 and HT 29 ) . ^^^ Coincubation of the IGF I / IGFBP 3 complex with MMP 7 restored IGF 1 mediated IGF IR phosphorylation and activation of Akt in these cell lines . ^^^ The IGF 1 signal recovered by MMP 7 protected against apoptosis induced by anoikis in 3T3 IGF IR cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To examine the effect of alcohol on IGF receptors in the liver and kidney , IGF 1 receptor mRNA was measured . ^^^ Alcohol decreased IGF 1 receptor mRNA in the liver and kidney . 4 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In colostrum fed calves , DEXA decreased ( P < 0 . 05 ) mRNA levels of IGF 1 ( esophagus , fundus , duodenum , and ileum ) , IGF 2 ( fundus ) , IGFBP 2 ( fundus ) , IGFBP 3 ( fundus ) , IGF1R ( esophagus , ileum , and colon ) , IGF2R ( fundus ) , GHR ( fundus ) , and InsR ( esophagus , fundus ) , but in formula fed calves DEXA increased mRNA levels of IGF 1 ( esophagus , rumen , jejunum , and colon ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here , molecular studies were undertaken to quantify expression of IGF 1 receptor ( IGF 1R ) mRNA in the preoptic area anterior hypothalamus ( POA AH ) and mediobasal hypothalamus ( MBH ) median eminence ( ME ) , the sites of GnRH perikarya and neuroterminals , respectively . ^^^ Moreover , the novel finding that the IGF 1R is expressed on GnRH perikarya in vivo suggests a potential direct anatomical locus where IGF 1 can regulate reproductive development and function . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Zinc ( Zn ( 2+ ) ) , a multifunctional micronutrient , was recently shown to lower the affinity of cell associated insulin like growth factor ( IGF ) binding protein ( IGFBP ) 3 and IGFBP 5 for both IGF 1 and IGF 2 , but to increase the affinity of the cell surface type 1 IGF receptor ( IGF 1R ) for the same two ligands . ^^^ In contrast , Zn ( 2+ ) increased IGF 1 , IGF 2 and R ( 3 ) IGF 1 binding to the IGF 1R by increasing ligand binding affinity on both P ( 2 ) A ( 2a ) LISN and L 6 myoblasts . ^^^ Soluble IGFBP 5 and IGFBP 4 depressed the binding of ( 125 ) 1 IGF 1 and ( 125 ) 1 IGF 2 to the IGF 1R , but did not affect binding of ( 125 ) 1 R ( 3 ) IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
DCA induced activation of the insulin receptor correlated with enhanced phosphorylation of insulin receptor substrate 1 , effects that were both blocked by the insulin receptor inhibitor AG 1024 and by expression of the dominant negative IGF 1 receptor ( K1003R ) , which inhibited in trans . ^^^ Expression of the dominant negative IGF 1 receptor ( K1003R ) also abolished DCA induced AKT activation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
At this stage the IGF 1 receptor message was highly expressed and visible in whole internal organ regions by whole mount in situ hybridization , while p 53 message was concentrated in the head portion and barely detectable in the trunk portion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study examined CLA regulation of TSU Pr 1 bladder cancer cell proliferation and apoptosis and the influence of CLA on IGF 1 receptor ( IGF IR ) signaling . ^^^ In addition , CLA decreased IGF 1 induced phosphorylation of IGF IR and IRS 1 , recruitment of the p 85 subunit of phosphoinositide 3 kinase to IRS 1 and phosphorylation of Akt and extracellular signal regulated kinase 1 / 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We demonstrated that AR activated the IGF 1 receptor ( IGF 1 R ) , which in turn induced the secretion of AR and IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSIONS : Mutations in the IGF IR gene that lead to abnormalities in the function or number of IGF 1 receptors may also retard intrauterine and subsequent growth in humans . . ^^^ IGF 1 receptor mutations resulting in intrauterine and postnatal growth retardation . ^^^ Fibroblasts cultured from the patient had decreased IGF 1 receptor function , as compared with that in control fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The direct effects of IGFBP 3 were determined in the presence of an IGF 1 receptor antagonist to eliminate its IGF 1 dependent effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Seventy two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase ( three variants ) , plasma cell differentiation antigen glycoprotein , human sorbin and SH 3 domain containing 1 , plasminogen activator inhibitor 1 , peroxisome proliferator activated receptor gamma 2 , protein tyrosine phosphatase 1B ( two variants ) , adiponectin ( two variants ) , IGF 1 , IGF 2 , IGF 1 receptor , and IGF 2 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In these protein kinase B / Akt 1 RNA interference cells , the signal molecules upstream of protein kinase B / Akt 1 , such as IGF 1 receptor and insulin receptor substrate 1 , were normally activated by insulin stimulation , whereas insulin stimulated phosphorylation of forkhead transcription factor ( FKHR ) , which is a downstream molecule of PKB / Akt 1 , was blocked . ^^^ Thus , protein kinase B / Akt 1 is an important signal mediator in IGF 1 receptor signal cascade for inducing adipocyte differentiation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The induced tumors showed upregulated expression of insulin receptor substrate 1 and phosphorylated forms of IGF 1 receptor and Akt , mimicking activated IGF signaling found in human MBs . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We also investigated the ability of these chimeras to bind and activate the IR exon 11+ isoform ( IR B ) and as a positive control , the IGF 1 receptor ( IGF 1R ) . ^^^ In contrast , the C and D domains of IGF 1 allow higher affinity binding to the IGF 1R than the analogous domains of IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 induced cellular invasiveness and IGF IR expression were significantly increased in clones overexpressing CEACAM 6 . ^^^ Using inhibitory anti IGF IR antibody , a requirement for IGF IR signaling in the enhanced invasiveness towards IGF 1 induced by CEACAM 6 overexpression was confirmed . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To determine the genetic relationship between S6Ks and the IGF 1 PI3K pathway , S6K transgenic and knockout mice were crossed with cardiac specific transgenic mice overexpressing the IGF 1 receptor ( IGF1R ) or PI3K mutants . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mice overexpressing a dominant negative IGF 1 receptor specifically in muscle ( MKR mice ) demonstrate severe insulin resistance with high levels of serum and tissue lipids and eventually develop type 2 diabetes at 5 6 wk of age . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF IR ) and its downstream signaling pathways Akt and ERK were phosphorylated by IGFBP 3 , whereas inhibition of IGF IR phosphorylation with tyrphostin AG 1024 suppressed the antiapopoptic effect of IGFBP 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To define precisely the signaling specific to the insulin receptor ( IR ) or the IGF 1 receptor , we have generated brown preadipocyte cell lines that lack either receptor ( insulin receptor knockout ( IRKO ) or insulin like growth factor receptor knockout ( IGFRKO ) ) . ^^^ In these cells , insulin stimulated IR homodimer phosphorylation , whereas IGF 1 activated both IGF 1 receptor homodimers and hybrid receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF IR ) is involved in numerous biological functions via its major downstream signaling molecules , extracellular signal regulated kinase ( ERK ) and phosphatidylinositol 3 ' kinase / Akt . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In a mixed culture system that employed IGF 1 receptor null murine embryo fibroblasts ( MEFs ) ( R ( ) cells ) to detect paracrine signals produced by MEFs expressing the human IGF 1 receptor ( R ( + ) cells ) , stimulation of R ( + ) cells provoked rapid activation of green fluorescent protein tagged ERK 2 in cocultured R ( ) cells . ^^^ These data suggest that the paracrine production of EGF receptor ligands leading to EGF receptor transactivation is a general property of IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NO production and protein expression of NOS , IGF 1 receptor ( IGF 1R ) and IGF binding protein 3 ( IGFBP 3 ) were measured by Griess assay and Western blot analysis , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cells grown on Transwell inserts were probed with antibodies to the Na ( + ) / K ( + ) ATPase alpha 1 subunit and either the alpha or beta subunits of the IGF 1 receptor and visualized in Z section using confocal microscopy . ^^^ Confocal analysis of Transwell cultured D 407 cells confirmed the apical localization of the Na ( + ) / K ( + ) ATPase alpha 1 subunit , characteristic of polarized RPE , with IGF 1 receptor alpha and beta subunits exhibiting a nonpolarized distribution . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The beta1A integrin forms a complex with the IGF IR and insulin receptor substrate 1 ( IRS 1 ) ; this complex does not promote IGF 1 mediated cell adhesion to laminin ( LN ) , although it does support IGF mediated cell proliferation . ^^^ Moreover , beta1C completely prevents IGF mediated cell proliferation and tumor growth by inhibiting IGF IR auto phosphorylation in response to IGF 1 stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Targeted mutations that affect components of this pathway , including the GH receptor , p66Shc , and the IGF 1 receptor ( IGF 1R ) , also extend life span ; mutations that affect IGF 1R or downstream components of the pathway decouple longevity effects from dwarfism . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Deletion of the pleckstrin and phosphotyrosine binding domains of insulin receptor substrate 2 does not impair its ability to regulate cell proliferation in myeloid cells . 32D IGF 1 receptor ( IR ) cells are IL 3 dependent myeloid cells that can be induced to differentiate into granulocytes by IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this connection : ( 1 ) changes in the expression pattern of components of the IGF system ( autocrine / paracrine expression of IGF 1 and 2 , overexpression of IGF IR , decreased expression of IGF binding proteins ( IGFBPs ) and of type 2 IGF receptor / cation independent mannose 6 phosphate receptor ( IGF II / M6PR ) and ( 2 ) increased serum concentrations of proteases that cleave the IGFBPs ( e . g . , cathepsin D ) were observed in patients with hepatocellular carcinomas ( HCC ) , in human hepatoma cell lines and in their conditioned culture medium , as well as in rodent models of hepatocarcinogenesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
DRG neurons express IGF 1 receptors ( IGF IR ) , and IGF 1 activates the phosphatidylinositol 3 kinase ( PI3K ) / Akt pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In nNOS / mice , there was a significant decrease in IGF 1 receptor immunoreactivity in the same cortical regions . ^^^ The immunoreactivity for IGF 1 receptor was differentially decreased in each layer in nNOS / mice . ^^^ In nNOS / cerebellum , IGF 1 receptor immunoreactivity was also significantly decreased in each layer of cerebellar cortex and cerebellar nuclei . ^^^ To clarify whether decreased expression of IGF 1 receptor in nNOS / mice was specific , the expression of other receptors for IGF 1 was also evaluated . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The assumption over the years has been that this family of proteins , having higher affinities for IGF 1 and IGF 2 than does the IGF IR , serves to block access of these ligands to the receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSIONS : WISH cells appeared to produce VEGF via a mechanism involving tyrosine kinase interaction with IGF 1 receptor , resulting in MAP kinase and PI 3 kinase activation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study examines the effect of ovariectomy and two doses of ovarian hormone treatment on IGF 1 receptor density in the adult rat by receptor autoradiography using ( 125 ) 1 IGF 1 as a ligand . ^^^ Our result showed that ovariectomy decreased IGF 1 receptor density in hippocampus , hypothalamus and parietal cortex compared to that of the sham operated group . ^^^ Treatment with low or high dose estrogen restored IGF 1 receptor density to the control levels in nearly all areas studied in this investigation . ^^^ It seems that low dose estrogen has more pronounced effect than the high dose in restoring IGF 1 receptor density . ^^^ On the other hand , progesterone treatment in high but not in low dose restored IGF 1 receptor density to that of the control . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To better understand the role of the insulin like receptors in mammalian lifespan regulation and ageing , we explored the phenotype of heterozygous IGF 1 receptor ( IGF1R ) knockout mice . ^^^ These IGF1R ( + / ) mutants were also more resistant to oxidative stress in vivo , and we identified a possible molecular pathway linking underphosphorylation of IGF 1 receptors to the lack of activation of p66Shc , a protein capable of increasing resistance to oxidative stress through regulation of a set of downstream genes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF IR ) has a central role in cell cycle progression as well as in the establishment of the transformed phenotype . ^^^ In addition , IGF 1 induced IGF IR and insulin receptor substrate 1 phosphorylation were greatly impaired in ATM deficient cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To assess the importance of the IGF 1 receptor ( IGF IR ) in brown adipocytes during fetal life , we have generated immortalized brown adipocyte cell lines from the IGF IR ( / ) mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF 1R ) and MT 1 MMP are synthesized as larger precursor proproteins , which require endoproteolytic activation by the proprotein convertases ( PCs ) furin / PC5 to gain full biological activity . ^^^ In conclusion , this study demonstrates that targeting furin like PCs and thus inhibiting IGF 1R activation is a novel target to inhibit IGF 1 mediated signaling and cell functions , such as IGF 1 induced MT 1 MMP / MMP 2 in VSMCs . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In MET cells in which the IGF IR was re expressed from a retroviral vector , the effects of DHT and IGF 1 on AR activity were similar to those seen in PRI cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tubulin and IGF 1 receptor mRNA expressions were quantified by real time polymerase chain reaction . ^^^ Expression of IGF 1 receptor mRNA increased significantly in the hypoxic animals both in the cerebrum and the cerebellum , but there was no change in expression of alpha tubulin mRNA . ^^^ CONCLUSIONS : This increase in IGF 1 receptor expression and growth cone content may be an adaptive response to hypoxia to maintain neurite growth by facilitating binding of IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
EP 2 stimulation failed to inhibit tyrosine phosphorylation either of IGF 1 receptor or IRS 1 ( insulin receptor substrate 1 ) , or activation of phosphoinositide 3 kinase or Akt in response to IGF 1 , but potently and dose dependently inhibited IGF 1 induced activation of cellular Rac activity and membrane ruffling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A newly developed bridging yeast tri hybrid assay showed that APS dimerizes JAK 2 , insulin receptor and IGF 1 receptor kinases using its SH 2 and dimerization domains . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , IGF 1 receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB 1 tg mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 induced a dose dependent increase in IGF 1R phosphorylation and in VEGF mRNA levels in cultured human RPE cells . ^^^ Somatostatin and octreotide , a somatostatin analogue , inhibited IGF 1 receptor ( IGF 1R ) phosphorylation and decreased VEGF production . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our analysis of early developmental processes in mammary tissue from mice that carry a targeted mutation in the IGF 1 receptor gene suggests that IGF dependent stimulation of cell cycle progression is more important to early mammary gland development than potential antiapoptotic effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have generated a humanized anti IGF IR antibody h7C10 that blocks in vitro IGF 1 and IGF 2 induced cell proliferation of MCF 7 breast cancer cells . ^^^ Analysis of the IGF 1 transduction cascade demonstrated that the humanized anti IGF IR antibody and its murine parental form block IGF 1 induced tyrosine phosphorylation , both its beta chain and IRS 1 tyrosine phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that IGF 1 activated the IGF 1R , insulin receptor substrate ( IRS ) 1 , phosphatidylinositol 3 kinase , and Akt in a time dependent manner in alphaT 3 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 immunoreactivity was abundant throughout surgically isolated human CNV tissues and RPE cells were immunopositive for IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibition of IGF 1R by the tyrphostin , AG 1024 , blocked endothelial tubulogenesis in vitro , confirming that IGF 1 functions as a regulator of angiogenesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and its high affinity receptor ( IGF1R ) are expressed in the developing inner ear and in the postnatal cochlear and vestibular ganglia . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We next demonstrate a physical association between CD 45 and IGF 1 receptor ( IGF 1R ) suggesting that CD 45 could be involved in the dephosphorylation of the IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of GD IgG can be reproduced by IGF 1 , appears to be mediated through the IGF 1 receptor , and is abolished with glucocorticoid treatment . ^^^ The observation that hyaluronan production is induced by GD IgG in fibroblasts suggests that the IGF 1 receptor and its activating antibodies may represent a key pathway through which important pathogenic events in thyroid associated ophthalmopathy are mediated . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PATIENT AND METHODS : The mono allelic loss of the IGF 1 receptor ( IGF1R ) gene was confirmed in a child with prenatal and severe postnatal growth retardation by fluorescence in situ hybridization , and was evaluated on the protein level in fibroblasts of the patient by FACS analysis and IGF cross linkage . ^^^ RESULTS : Levels of GH , IGF 1 , and IGFBP 3 were above the 95th percentile in the serum of the 3 year old girl with a mono allelic deletion of the IGF1R gene , suggesting IGF 1 resistance . ^^^ Mono allelic expression of the IGF 1 receptor does not affect IGF responses in human fibroblasts . ^^^ OBJECTIVE : It has been suggested that mono allelic deletion of the IGF 1 receptor gene is causally related to severe intrauterine and postnatal growth deficiency whereas no IGF 1 resistance was observed in the patients ' fibroblasts . ^^^ In the patient ' s fibroblasts the IGF 1 receptor concentration was half that in control cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In cerebellar granule neurons , ethanol inhibited autophosphorylation of the apo IGF IR , but did not reverse IGF IR phosphorylation after IGF 1 stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Quantitation of local transcript levels for mRNAs encoding IGF 1 and IGF 1 receptor ( IGF IR ) also reveals significant differences in expression of these transcripts in atrial tissue of SpDwf animals compared with controls . ^^^ In SpDwf rats , the abundance of IGF IR mRNA remains elevated at many postnatal ages , whereas mRNA encoding IGF 1 is maintained only in older animals . ^^^ Physiological concentrations of IGF 1 cause two to threefold increases in LVA current density in primary cultures of atrial myocytes , and this effect is blocked by an antisense oligonucleotide targeting the IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The costimulatory effect of GH on steroidogenesis was abolished by treatment with picropodophyllin , a specific inhibitor of the IGF 1 receptor , indicating that the action of GH is mediated via IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Caki 2 expressed higher levels of IGF IR and proliferated more vigorously to added IGF 1 , IGF 1 analogues des ( 1 3 ) IGF 1 , LongR3IGF 1 and IGF 2 compared to SK RC 52 . ^^^ Interestingly , soluble IGF 1 receptor resulted in strong growth inhibition of SK RC 52 , while no marked effect on Caki 2 was observed . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Upon binding of IGF 1 or IGF 2 , IGF 1R , a tyrosine kinase , phosphorylates tyrosine residues on two major substrates , IRS 1 and Shc , which subsequently signal through the Ras / Raf and PI 3 kinase / AKT pathways ( 7 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mice that express a dominant negative IGF 1 receptor , specifically in skeletal muscle ( MKR mice ) , exhibit severe insulin resistance , hyperinsulinemia , dyslipidemia , and hyper glycemia . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed IGF 1 receptor expression in all human pulp samples . t test revealed statistically significant higher expression in the pulps from teeth having incomplete root development ( P < 0 . 005 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Weakening of cell matrix adhesion is blocked significantly ( p < 0 . 01 ) by the catalytically inactive IGF 1 receptor ( IGF IR ) and the phosphoinositide 3 kinase ( PI 3 kinase ) inhibitor LY 294002 , but it is unaffected by mitogen activated protein kinase kinase inhibitor UO 126 and Src kinase inhibitor PP 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transfection of either wild type or a constitutively active mutant of the IGF 1 receptor augments AR mediated transcription . ^^^ An antisense construct of beta catenin that decreases the cellular level of beta catenin can reduce IGF 1 receptor mediated enhancement of AR activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A correlation between increased expression ( at mRNA and protein levels ) for IGF 1 and IGF 1R and decreased apoptosis were found in large cell carcinomas and adenocarcinomas . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Mutational analysis of the interaction between insulin receptor and IGF 1 receptor with c Crk and Crk L in a yeast two hybrid system . ^^^ We have employed a yeast two hybrid approach and mutational analysis to dissect the capabilities of the insulin receptor and the IGF 1 receptor to directly associate with Crk isoforms . ^^^ In contrast , interaction of the IGF 1 receptor with the Crk IISH 2 domain was only detectable when Crk 2 was truncated in its C terminal part , indicating the transient nature of this interaction . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We report here that activation of the type 1 insulin like growth factor receptor ( IGF IR ) by IGF 1 increases transcription from the ribosomal DNA ( rDNA ) promoter in both myeloid cells and mouse fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The steroid responsive human LNCaP prostate cancer cells , containing a functional but mutated androgen receptor ( AR ) , were used to compare effects of DHEA with those of T , DHT , and E 2 on cell proliferation and protein and / or gene expression of AR , prostate specific antigen ( PSA ) , IGF 1 , IGF 1 receptor ( IGF IR ) , IGF 2 , IGF binding proteins 2 , 3 , and 5 , ( IGFBPs 2 , 3 , and 5 ) , and estrogen receptor beta ( ERbeta ) . ^^^ All four hormones increased gene and / or protein expression of PSA , IGF IR , IGF 1 , and IGFBP 2 and decreased that of AR , ERbeta , IGF 2 , and IGFBP 3 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expression of insulin like growth factors 1 ( IGF 1 ) and 2 ( IGF 2 ) and insulin like growth factor 1 receptor ( IGF IR ) was studied in 137 clear cell , 23 chromophobe , and 20 papillary renal cell carcinomas ( RCCs ) using a tissue microarray technique . ^^^ Expression of IGF 1 and IGF IR was not related to tumor stage , grade , or prognosis . ^^^ The expression of IGF 1 together with its receptor , IGF IR , provides evidence for the existence of an autocrine paracrine loop of tumor cell stimulation in RCC and makes this type of cancer a candidate for therapeutic strategies aimed to interfere with the IGF pathway . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blocking of the IGF 1 signaling pathway targeting the IGF 1 receptor ( IGF 1R ) provides a potential treatment strategy for restenosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We studied by real time reverse transcription PCR , whether there are differences in the abundance of mRNA coding for IGF 1 , IGF 2 , IGFBP 2 , IGFBP 3 , IGF 1R , IGF 2R , GHR , and InsR in compartmentalized layers ( fractions ) of jejunum and ileum of 5 d old calves fed colostrum . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Fibroblast conditioned medium , as well as exogenous IGF 1 , increased protein synthesis in cardiac myocytes , and this increase was inhibited by antibodies against IGF 1 and IGF 1 receptor , IGF binding protein 3 , and IGF 1 receptor antagonist . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These mice demonstrated significantly increased mammary epithelial cell proliferation ( P < 0 . 003 ) , cyclin D 1 expression ( P = 0 . 002 ) , IGF 1 receptor protein expression ( P = 0 . 026 ) , mammary gland mass ( P < 0 . 05 ) , and altered expression of CCAAT / enhancer binding protein isoforms ( P = 0 . 029 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The dogma that IGF 1 stimulates pancreatic islet growth has been challenged by combinational targeting of IGF or IGF IR ( IGF receptor ) genes as well as beta cell specific IGF IR gene deficiency , which caused no defect in islet cell growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This is evidenced by dwarfism in states of congenital IGF 1 deficiency , Igf 1 gene mutation / deletions or knockouts , and in Laron syndrome ( LS ) , due to GH receptor gene mutations / deletions or IGF 1 receptor blocking . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This has led to the development of novel IGF 1 receptor targeting therapies which have impressive antineoplastic activity in experimental systems . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this paper , we review strategies of the genetic blockade of IGF 1 / IGF 1R that validate this receptor as a promising anticancer target . ^^^ Blocking for IGF 1R suppressed tumorigenicity both in vitro and invivo and effectively blocked both IGF 1 and IGF 2 induced activation of Akt 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On the other hand , decreased IGF action , subsequent to the down regulation of IGF 1 receptor expression , is associated with advanced , metastatic disease . ^^^ This decrease in IGF 1 receptor may confer a survival advantage to prostate cancer cells that have entered the circulation by making them resistant to the differentiative effects of IGF 1 at metastatic sites such as bone . ^^^ The molecular mechanisms that effect IGF 1 receptor down regulation appear to involve novel oncogenic functions of the Wilms ' tumour suppressor , as well as novel actions of the androgen receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In conclusion , human placentas from pregnancies complicated by IUGR are characterized by decreased IGF 1 receptor content , selective impairment of the IRS 2 / phosphatidyl inositol 3 kinase pathway , and reduced p 38 and c Jun N terminal kinase activation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The type 1 insulin like growth factor receptor ( IGF 1R ) is a receptor tyrosine kinase that mediates insulin like growth factor 1 ( IGF 1 ) and IGF 2 signalling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Gene expression of IGF 1 and IGF 1 receptor ( IGF 1R ) in the ischemic brain tissue were measured at 2 and 7 days after MCAo using reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Immunohistochemistry was performed to measure the expression of bromodeoxyuridine ( BrdU ) , doublecortin ( DCX ) , IGF 1 and IGF 1R at 7 , 14 and 30 days after MCAo . ^^^ MAB 1281 labeled hMSCs entered the ischemic brain and increased time dependently . hMSC treatment significantly increased IGF 1 mRNA and BrdU ( + ) , DCX ( + ) , IGF 1 ( + ) and IGF 1R ( + ) cells compared to PBS treated rats ( p < 0 . 05 ) . ^^^ IGF 1 and IGF 1R may contribute to improved functional recovery and increased neurogenesis after treatment of stroke with hMSCs . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study examined the role of crosstalk between estrogen receptor ( ER ) alpha and the IGF 1 receptor as a critical mediator of hormone and growth factor dependent neurite outgrowth in a homogenous cell system . ^^^ We used control PC 12 cells and PC 12 cells stably transfected with ER alpha , both of which express IGF 1 receptor . ^^^ Cells were treated for 1 week with vehicle , 1 nM E ( 2 ) or 100 ng / ml IGF 1 alone or with E ( 2 ) or IGF 1 in the presence of either the IGF 1 receptor antagonist JB 1 or the ER antagonist ICI 182 , 780 . ^^^ The ER and IGF 1 receptor antagonists similarly blocked the E ( 2 ) induced increase in neurite lengths in ER alpha transfected cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both cell lines exhibit androgen responsive patterns of IGF 1 receptor ( IGF IR ) expression , activation , and signaling to insulin receptor substrate 2 and AKT . ^^^ However , C 4 2 cells express higher levels of IGF IR mRNA and protein and exhibit enhanced IGF 1 mediated phosphorylation and downstream signaling under androgen deprived conditions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Val44Met IGF 1 exhibits a 90 fold decrease in type 1 IGF receptor ( IGF 1R ) binding compared with wild type human IGF 1 and only poorly stimulates autophosphorylation of the IGF 1R . ^^^ To our knowledge , our results provide the first structural study of a naturally occurring mutant human IGF 1 associated with growth and developmental abnormalities and identifies Val 44 as an essential residue involved in the IGF IGF 1R interaction . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results show that maternal undernutrition increases pancreatic IGF 1 expression and islet IGF 1 receptor content in undernourished fetuses , whereas hepatic IGF 1 expression and serum IGF 1 levels were decreased . ^^^ In conclusion , in undernourished fetuses the increased beta cell mass can be related to the stimulation of replicative beta cell response due to locally increased pancreatic IGF 1 mRNA ; this effect is perhaps potentiated or favored by the enhanced islet IGF 1 receptor content and pancreatic IGFBP 2 gene expression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We briefly compare calorie restriction , GHRH R and Pit 1 mutants with knockout phenotypes of GH receptor , IGF 1 receptor and p66Shc , to make some general conclusions . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Human estrogen receptor positive breast cancer cells typically display an elevated level of cyclin D 1 protein because of the overexpression of CCND 1 messenger RNA ( mRNA ) and an elevated level of insulin like growth factor 1 ( IGF 1 ) receptor ( IGF1R ) because of the overexpression of IGF1R mRNA . ^^^ RESULTS : IGF1R overexpressing MCF 7 cells internalized the fluorescein chelator CCND 1 PNA IGF 1 peptide but not the mismatched control peptide . ^^^ The chelator CCND 1 PNA IGF 1 peptide but not the control peptide lowered the level of cyclin D 1 protein in IGF1R overexpressing MCF 7 xenografts in nude mice after intratumoral injection . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Pretreatment with IGF 1 receptor ( IGF IR ) antibody blocked IGF 1 altered IGF IR activity and Rstn mRNA levels . ^^^ These data demonstrate that IGF 1 downregulates Rstn gene expression via IGF IR dependent and MEK 1 , p 38 MAPK , and phosphoinositide 3 kinase independent pathways and likely modifies the distribution of Rstn protein between the intracellular and extracellular compartments via a p 38 MAPK dependent pathway . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PURPOSE : The aim of this study was to characterize the relationship of insulin like growth factor ( IGF ) 2 expression with IGF 1 , IGF 1 receptor ( IGF IR ) , cyclooxygenase 2 ( COX 2 ) , and matrix metalloproteinase ( MMP ) 7 in early colorectal carcinogenesis . ^^^ EXPERIMENTAL DESIGN : With the semiquantitative reverse transcriptase PCR , 90 human colorectal tumor tissues ( 63 adenomas and 27 submucosal pT 1 cancers ) were analyzed for IGF 2 , IGF IR , IGF 1 , COX 2 , and MMP 7 expression . ^^^ IGF 2 expression was positively correlated with the expression of IGF IR and IGF 1 . ^^^ COX 2 and MMP 7 mRNA expression was detected in 42 . 2 % and 77 . 8 % of the tumor tissues , respectively , and both were positively correlated with IGF 1 , IGF 2 , and IGF IR expression . ^^^ CONCLUSIONS : IGF 2 , in conjunction with IGF IR , IGF 1 , COX 2 , and MMP 7 , seems to play a key role in the early stage of colorectal carcinogenesis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin concentrations sufficiently high to interact with the IGF 1 receptor are routinely used to induce ATDC 5 cells to differentiate . ^^^ In contrast , IGF 1 mediated Akt activation was unchanged by differentiation , indicating intact upstream IGF 1 receptor signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that expression of caveolin 1 in human breast cancer cells enhances matrix independent cell survival that is mediated by upregulation of IGF 1 receptor expression and signaling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) is a multifunctional transmembrane tyrosine kinase that has been implicated in neoplastic transformation . ^^^ In hormone dependent breast cancer cells , IGF IR and IRS 1 are often co expressed with the estrogen receptor alpha ( ERalpha ) , and IGF 1 and ER systems are engaged in a powerful functional cross talk . ^^^ Most notably , activation of ERalpha upregulates the expression of IRS 1 , IGF IR , and IGF 1 , which results in amplification of IGF 1 responses . ^^^ In contrast , in ERalpha negative breast cancer cells and tumors , the levels of IGF IR and IRS 1 are often decreased and IGF 1 is non mitogenic . ^^^ Interestingly , some non mitogenic IGF 1 responses , such as migration and invasion are retained in the absence of ERalpha , suggesting that IGF IR function in breast cancer cells might depend on the ERalpha status . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor ( IGF ) signalling pathway has been highly conserved in animal evolution and , in mammals and Xenopus , plays a key role in embryonic growth and development , with the IGF 1 receptor ( IGF 1R ) being a crucial regulator of the signalling cascade . ^^^ This is supported by the expression of IGF 1 , IGF 2 and IGF 1R in shield stage zebrafish embryos and the demonstration that IGF signalling influences expression of BMP2b , a gene that plays an important role in zebrafish pattern formation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptors ( IGF IR ) and insulin receptors ( IR ) in endothelial cells might respond to altered levels of IGF 1 and insulin , resulting in altered endothelial function in diabetes . ^^^ IGF IR phosphorylation was stimulated by 10 ( 10 ) to 10 ( 8 ) M IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To assess the role of the IGF 1 receptor ( IGF IR ) in hepatocarcinogenesis , we generated conditional mutant mice that overexpressed c myc and were knocked out for IGF IR specifically in the liver . ^^^ IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Growth hormone receptor ( GHR ) mRNA was most abundant in mature hypertrophic cells and undetectable in resting cells ; IGF 1 receptor ( IGF IR ) mRNA was detectable in resting cells but two fold higher in the fraction adjacent to cells possessing high GHR mRNA , while proliferating and resting chondrocytes had elevated IGF 1 mRNA levels when compared to that for hypertrophic chondrocytes . ^^^ The growth plate distribution of IGF IR and GHR mRNA implies distinct roles for circulating IGF 1 vs . paracrine produced IGF I . . ^^^ Fractionation of growth plate chondrocytes : differential expression of IGF 1 and growth hormone and IGF 1 receptor mRNA in purified populations . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Both GH and IGF 1 stimulated the accumulation of IGF 1 receptor mRNA in the most immature proliferative zone cells but did not alter the accumulation of IGF binding protein 4 mRNA in any fraction . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RACK 1 mediated integration of adhesion and insulin like growth factor 1 ( IGF 1 ) signaling and cell migration are defective in cells expressing an IGF 1 receptor mutated at tyrosines 1250 and 1251 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
By reverse transcriptase polymerase chain reaction ( RT PCR ) analysis , mRNA of IGF 1 and 2 , IGF 1 receptor ( IGF IR ) , insulin receptor ( insulin R ) , and IGF binding protein ( IGFBP ) 2 , 3 , 4 , 5 , and 6 was detected in the taste bud containing epithelium of the circumvallate papillae of mice . ^^^ These data reveal that IGF 1 and 2 might be produced in taste bud cells and ( or ) surrounding lingual epithelium and act through IGF IR and insulin R locally in a paracrine and autocrine manner . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have determined whether signalling through the IGF 1 receptor ( IGF 1R ) pathway plays a role in the gefitinib acquired resistance phenotype . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin deficiency downregulated heat shock protein 60 and IGF 1 receptor signaling in diabetic myocardium . ^^^ Heat shock protein ( Hsp ) 60 and IGF 1 receptor signaling protect cardiac muscle against injury . ^^^ The abundance of cardiac IGF 1 receptor can be upregulated by Hsp 60 , but how diabetes modulates cardiac muscle Hsp 60 has not yet been defined . ^^^ We investigated the changes of Hsp 60 and IGF 1 receptor signaling in the diabetic myocardium and studied how diabetes modulates Hsp 60 and IGF 1 receptor in diabetic myocardium . ^^^ In the streptozotocin ( STZ ) induced diabetic rat , downregulation of Hsp 60 and IGF 1 receptor occurred 4 days after induction of diabetes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To evaluate the biological effects of the GH / IGF 1 axis on muscle growth , we administrated recombinant human GH to mice , which lack IGF 1 function specifically in skeletal muscle , due to the overexpression of a dominant negative IGF 1 receptor in this tissue ( MKR mice ) . ^^^ Taken together , these data suggest that the in vivo effects of GH on muscle mass and strength are primarily mediated by activation of the IGF 1 receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present work , we investigated the potential of the third member of the family , insulin receptor related receptor ( IRR ) , to associate with known interaction partners of the InsR and the IGF 1 receptor in a yeast two hybrid assay . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Presence of MHC 1 in rat glioma cells expressing antisense IGF 1 receptor RNA . ^^^ The supposed immunogenic character of glioma cells transfected with antisense IGF 1 Receptor ( IGF 1 R ) expression vector was tested for the presence of MHC 1 currently present in cells of IGF 1 antisense type . ^^^ C 6 rat glioma cell line was comparatively transfected in vitro with IGF 1 antisense ( pMT Anti IGF 1 ) or IGF 1 Receptor antisense ( pMT Anti IGF 1 R ) expression vectors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Key features of the structures include ( 1 ) a disulphide bond ladder that binds to IGF and partially masks the IGF residues responsible for type 1 IGF receptor ( IGF IR ) binding , ( 2 ) the high affinity IGF 1 interaction site formed by residues 39 82 in a globular fold , and ( 3 ) CBP 4 interactions . ^^^ Although CBP 4 does not bind individually to either IGF 1 or NBP 4 , in the ternary complex , CBP 4 contacts both and also blocks the IGF IR binding region of IGF I . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The growth hormone insulin like growth factor axis revisited : lessons from IGF 1 and IGF 1 receptor gene targeting . ^^^ In a separate transgenic mouse we created a model of severe insulin resistance and type 2 diabetes by the overexpression of a dominant negative IGF 1 receptor in skeletal muscle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated whether insulin like growth factor ( IGF ) 2 may elicit a different gene expression response from insulin in cells expressing only IR A and lacking IGF 1 receptor ( R / IR A cells ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : The insulin like growth factor system , which includes insulin like growth factors ( IGF 1 and IGF 2 ) , IGF receptors ( IGF IR and IGF IIR ) and IGF binding proteins ( IGFBPs ) , plays an important role in epithelial growth , anti apoptosis and mitogenesis . ^^^ DISCUSSION : The growth promoting effects of IGF 1 and IGF 2 on cancer cells are mediated through the IGF IR , which is a tyrosine kinase and cancer cells with a strong tendency to metastasise have a higher expression of the IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We hypothesized that scintigraphic detection of MYC peptide nucleic acid ( PNA ) probes with an IGF 1 peptide loop on the C terminus , and a [ 99mTc ] chelator peptide on the N terminus , could measure levels of MYC mRNA noninvasively in human IGF1R overexpressing MCF 7 breast cancer xenografts in nude mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The functional interactions between IGF 1 receptor , lysophosphatidic acid ( LPA ) signaling , and EGF receptor were observed , both direct and / or indirectly on phospho Akt , phospho Erk1 / 2 , and phospho ribosomal S6 . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Western blot analysis revealed an approximate 200 % increase in insulin receptor protein levels and an approximate 50 % increase in IGF 1 receptor protein levels in the hippocampus of Pcmt 1 / mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) , despite their well known roles in cell survival and proliferation , can also weakly enhance apoptosis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To elucidate the potential molecular mechanisms leading to the increase in adrenal growth , we examined adrenal expression of the cell cycle regulatory proteins ( cyclin D 1 ) and cyclin kinase inhibitory proteins ( p16ink , p21Cip ) , and insulin like growth factor 2 ( IGF 2 ) , IGF binding protein 2 ( IGFBP 2 ) and IGF 1 type 1 Receptor ( IGF1R ) from fetuses infused with metyrapone or vehicle for 15 days . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Growth hormone ( GH ) , insulin like growth factors 1 and 2 ( IGF 1 and IGF 2 ) and their associated binding proteins and transmembrane receptors ( GHR , IGF1R and IGF2R ) play an important role in the physiology of mammalian growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunohistochemically , pT1a RCCs were characterized by strong expression of p 27 ( 79 % ) , bcl 2 ( 67 % ) , MUC 1 ( 87 % ) , insulin like growth factor ( IGF ) 1 ( 71 % ) and CD 10 ( 88 % ) , as well as moderate expression of IGF 1 receptor ( 43 % ) and low expression of epidermal growth factor receptor ( EGFR , 20 % ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , to begin to understand the mechanisms responsible for the beneficial effects of blueberries , we assessed changes in hippocampal plasticity parameters such as hippocampal neurogenesis , extracellular receptor kinase activation , and IGF 1 and IGF 1R levels in blueberry supplemented aged animals . ^^^ Our results show that all these parameters of hippocampal neuronal plasticity are increased in supplemented animals and aspects such as proliferation , extracellular receptor kinase activation and IGF 1 and IGF 1R levels correlate with improvements in spatial memory . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNA expressions of IGF , IGF 1 receptor , and IGF binding protein ( IGFBP ) 2 were quantitatively analyzed by reverse transcription ( RT ) PCR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the same light , we review basic research from our laboratory showing that IGF 1R differentially regulates the expression of breast cancer progression genes when pre malignant breast epithelial cells were stimulated with insulin like growth factor 1 ( IGF 1 ) over time . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here , we report that induction of sCLU is delayed , peaking 72 h after low doses of ionizing radiation , and is dependent on the up regulation of insulin like growth factor 1 as well as phosphorylation dependent activation of its receptor ( IGF 1 and IGF 1R , respectively ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Results from Northern analysis and tests using IGF 1 analogs suggest that IGF 1 effects are mediated through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study therefore examined the influence of maternal nutrient restriction ( NR ) , targeted at specific periods of kidney development during early to mid gestation , on the mRNA abundance of receptors for glucocorticoid ( GCR ) , growth hormone ( GHR ) and insulin like growth factors 1 ( IGF IR ) and 2 ( IGF IIR ) , and the IGF 1 and 2 ligands . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This mutant was equipotent compared to native IGFBP 5 in its ability to inhibit both protein synthesis and cell migration responses to IGF 1 plus TS 1 thus excluding the possibility that IGFBP 5 was inhibiting the response to TS 1 and IGF 1 by inhibiting IGF 1 binding to the IGF 1 receptor . ^^^ When the IGFBP 5 mutant that did not bind to IGF 1 was incubated with TS 1 and IGF 1 , it inhibited the capacity of TS 1 to enhance the IGF 1 receptor phosphorylation and MAP kinase activation in response to IGF 1 . ^^^ In contrast , the IGFBP 5 mutant that did not bind to TS 1 had no effect on IGF 1 stimulated IGF 1 receptor phosphorylation or MAP kinase activation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Further , we applied molecular biology techniques to determine the present of local gene expression of IGF 1R and IGF 1 . ^^^ Furthermore , the RT PCR experiment demonstrates clearly that IGF 1 and IGF 1R was expressed together in the porcine pancreas . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Decorin addition causes IGF 1 receptor phosphorylation and activation , which is followed by receptor down regulation . ^^^ The physiological relevance of the decorin / IGF 1 receptor interaction was corroborated in two animal models ( e . g . inflammatory angiogenesis in the cornea and unilateral ureteral obstruction ) . ^^^ In both models the IGF 1 receptor was up regulated in decorin deficient mice compared with controls and the up regulation could not compensate the decorin deficiency in the disease models . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cross talk from membrane localized ERs to nuclear ERs can be mediated through growth factor receptor tyrosine kinases , such as epidermal growth factor receptor and IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , it was recently suggested that p66Shc , which is an adaptor molecule of the IGF 1 receptor , might play a critical role in this synergistic effect . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Suppressor of cytokine signaling 1 suppresses muscle differentiation through modulation of IGF 1 receptor signal transduction . ^^^ However , the mechanism ( s ) of SOCS 1 induction by insulin like growth factor ( IGF ) 1 and a role of SOCS 1 on IGF 1 receptor mediated signaling are not clarified . ^^^ Collectively , these findings suggest that SOCS 1 suppresses muscle differentiation through negative feedback regulation of IGF 1 receptor mediated signaling . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunohistochemistry revealed the specific localization of the IGF 1 receptor in Hertwig ' s epithelial root sheath ( HERS ) in the tooth root . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study initially confirmed in mouse osteoblast cultures that PTH treatment increased IGF 1 mRNA and protein levels and alkaline phosphatase activity , which were accompanied by phosphorylations of IGF 1 receptor , insulin receptor substrate ( IRS ) 1 and IRS 2 , essential adaptor molecules for the IGF 1 signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 and IGF 1 receptor ( type 1 ) mRNAs were detected in the endometrial stromal cells . ^^^ IGF 1 receptor is a tyrosine kinase receptor , and treatment with genistein , a tyrosine kinase inhibitor , reduced IGF 1 induced BrdU uptake in the endometrial stromal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
BACKGROUND : The colocalization of insulin like growth factor binding protein 3 ( IGFBP 3 ) and IGF 1 receptor ( IGF IR ) in the basal / germinative layer of the epidermis suggests a key role in modulating epidermal homeostasis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Increased contractility of cardiomyocytes from copper deficient rats is associated with upregulation of cardiac IGF 1 receptor . ^^^ Cu deficiency depressed serum and heart IGF 1 and heart IGFBP 3 protein levels and increased cardiac IGF 1 receptor protein . ^^^ These changes were largely inhibited by use of H 1356 , an IGF 1 receptor blocker . ^^^ We conclude that enhanced sensitivity to IGF 1 , as indicated by an increase in IGF 1 receptor protein , accounts for the increased contractility of Cu deficient cardiomyocytes and may presage cardiac failure . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONCLUSIONS : The suggestion concerning higher susceptibility of osteosarcoma ' s with higher aneuploidy on IGF 1 should be verified by longer clinical observation concerning survival rate in the two groups ; the group with higher and the group with lower aneuploidy and IGF IR expression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Effect of tensile force on the expression of IGF 1 and IGF 1 receptor in the organ cultured rat cranial suture . ^^^ In this study , we investigated changes in the expression of IGF 1 and IGF 1 receptor and cell proliferation when a continuous tensile force was applied to the cranial suture of cultured rat calvaria . ^^^ By using in situ hybridisation , we also confirmed that IGF 1 and IGF 1 receptor mRNAs were localized in osteoblast like and fibroblastic cells subjected to the tensile force . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here , we show than in adult rat supraoptic nucleus ( SON ) , IGF 1 receptor immunoreactivity is present in neurons , whereas IGF 1 immunoreactivity is found principally in astrocytes and more moderately in neurons . ^^^ Recordings of acutely isolated SON neurons showed that this inhibition occurs through two rapid and reversible mechanisms , both involving the neuronal IGF 1 receptor but different intracellular messengers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The purpose of this study was to determine whether the novel IGF 1 receptor ( IGF IR ) kinase inhibitor , NVP ADW 742 , sensitizes SCLC cell lines to etoposide and carboplatin , which are commonly used in the treatment of SCLC . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since insulin like growth factor 1 ( IGF 1 ) is a most potent stimulator of collagen biosynthesis in fibroblasts the mechanism of IL 1 dependent inhibition of collagen biosynthesis may be related to inhibition of IGF IR expression and signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate the contribution of GH , IGF 1 and apoptosis to growth plate function , the expression of GH receptor ( GHR ) and IGF 1 receptor ( IGF IR ) mRNA were evaluated by in situ hybridization in fractionated costochondral growth plates of growing rats ( at 2 , 4 , and 7 weeks ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Levels of immunoreactive IGF 1 , IGF 2 and IGF 1R protein were most abundant on the apical surface of the endometrial LE and GE . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
All of the Meg1 / Grb10 transgenic mice showed growth retardation after weaning ( 3 4 weeks ) , which indicates that ectopic overexpression of Meg1 / Grb10 inhibits postnatal growth that is mediated by IGF 1 via IGF1R . ^^^ These results suggest that Meg1 / Grb10 inhibits the function of both insulin and IGF 1 receptors in these cells , since a similar phenotype has been reported for Ir and Igf1r double knockout mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we show that androgens up regulate insulin like growth factor 1 receptor ( IGF IR ) expression and sensitize prostate cancer cells to the biological effects of IGF 1 . ^^^ In accordance with IGF IR up regulation , treatment with the nonmetabolizable androgen R 1881 sensitized LNCaP cells to the mitogenic and motogenic effects of IGF 1 , whereas an IGF IR blocking antibody effectively inhibited these effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
A plasmid containing a fragment of porcine IGF 1 receptor ( pIGF IR ) gene cloned downstream of EGFP sequence was constructed and cotransfected with pIGF IR / siRNAs in HEK 293T human cell line . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : This antibody blocks binding of IGF 1 to its receptor ( IC ( 50 ) 1 . 8 nmol / L ) , IGF 1 induced receptor autophosphorylation ( IC ( 50 ) 0 . 42 nmol / L ) and induced the down regulation of IGF 1R in vitro and in tumor xenografts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to investigate this relationship in a mammalian species , a series of experiments were carried out with a mouse model heterozygous for a mutation in the IGF 1 receptor gene . ^^^ Resistance to oxidative stress in these mutant animals could be caused by decreased phosphorylation of molecules downstream of the IGF 1 receptor in the IGF 1 signalling pathway , one of which is thought to be p66shc . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The inactivating nature of the mutation was proven by functional analysis demonstrating a 90 fold reduced affinity of recombinantly produced for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , we confirm that there is no local down regulation of IGF 1 and IGF IR mRNA in aged muscle tissue ; on the contrary , the most sarcopenic individuals showed significantly higher local expression of IGF 1 mRNA . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 dose dependently increased the phosphorylation level of Erk1 / 2 by 1 . 2 5 . 3 fold and that of IGF 1 receptor ( IGF IR ) by 2 4 fold . ^^^ Recent studies have implicated a role for integrin in the regulation of IGF IR phosphorylation and IGF 1 signaling . ^^^ Shear stress also significantly reduced the amounts of co immunoprecipitated SHP 2 and 1 with IGF IR , suggesting that the synergy between shear stress and IGF 1 in osteoblast proliferation involves integrin dependent recruitment of SHP 2 and 1 away from IGF IR . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In six of nine human MB cell lines IGF 2 displayed a growth promoting effect that was mediated mainly through the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , the IGF 1 receptor antagonist , JB 1 , blocked the effect of E ( 2 ) on prolactin synthesis and MAPK activation , as did the oestrogen receptor antagonist ICI 182 780 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In this study , we have mapped the distribution of putative IGF 1 receptor ( IGF IR ) binding sites in the brain of the brown trout using both ligand binding in vitro autoradiography and immunohistochemistry . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , interplay between heat shock protein and IGF 1 receptor signaling has been identified and this new paradigm might be involved in the development of diabetic cardiomyopathy . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptors ( IGF IR ) were identified by immunohistochemistry in biopsies taken from patients with different AIDS / HIV related KS stages and on KSIMM cells ( an established KS derived cell line ) . ^^^ Moreover , specific blockade of the receptor ( either by alpha IR 3 antibody or by picropodophyllin , a recently described selective IGF IR tyrosine phosphorylation inhibitor ) induced KSIMM apoptosis , suggesting that IGF IR agonists ( IGF 1 and 2 ) mediate antiapoptotic signals for these cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The relationship of oestrogen receptor alpha with IGF 1 receptor through the mitogen activated protein kinase and the phosphoinositide 3 kinase signalling pathways may represent the point of convergence used by these two factors to cooperatively modulate neuritic growth , synaptic plasticity , neuroendocrine events , reproductive behaviour and neuronal survival . ^^^ In addition , Akt and glycogen synthase kinase 3beta are key molecular targets to explain the interaction of oestrogen and IGF 1 receptor signalling in the promotion of neuroprotection . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor was found in seminal plasma from fertile and infertile men , but no IGF 1 receptor was observed in sperm from patients with a history of more failed fertilization . ^^^ The presence of the IGF 1 receptor in the plasma membrane of human sperm is proposed as a future tool for male sterility assessment . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In an attempt to understand the mechanism of chemo resistance , we investigated the roles of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptors ( IGF IR ) , and their relationship with the apoptotic response of two glioma cell lines to etoposide , a chemotherapeutic agent for malignant gliomas . ^^^ The anti apoptotic effect of IGF 1 and IGF IR might be related to the chemo resistance of glioma to chemotherapeutic agents . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
On GD 19 , immunolocalization of IGF 1 receptor protein demonstrated an increase in cytoplasmic expression in the mesenchymal and epithelial cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To test this hypothesis further , we examined the effects of 10 daily s . c . injections of IGF 1 on NMDA receptor subunits ( NR 1 , NR2A , and NR2B ) , GH receptor ( GHR ) , GH binding protein ( GHBP ) and type 1 IGF receptor ( IGF 1R ) gene transcripts in the hippocampus . ^^^ The GHR mRNA increased in young rats , mimicking the effect of GH , while the IGF 1R mRNA was decreased in the older group of rats after IGF 1 treatment . ^^^ Age related effects of IGF 1 on the NMDA , GH and IGF 1 receptor mRNA transcripts in the rat hippocampus . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF 1R ) is expressed on T and B lymphocytes , and the expression of the insulin and IGF 1 signaling machinery undergoes defined changes throughout lineage differentiation , offering a putative role for IGF 1 in the regulation of immune responses . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Rescue of ligand binding of a mutant IGF 1 receptor by complementation . ^^^ The IGF 1 receptor binds IGF 1 with complex kinetics characterized by a curvilinear Scatchard plot , suggesting receptor heterogeneity and apparent negative cooperativity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Tectorigenin and several other phytochemicals downregulated PDEF , PSA and IGF 1 receptor mRNA expression in vitro . ^^^ Furthermore , PSA secretion and IGF 1 receptor protein expression were diminished , and hTERT mRNA expression and telomerase activity decreased after tectorigenin treatments . ^^^ The downregulation of PDEF , PSA , hTERT and IGF 1 receptor gene expression by tectorigenin demonstrates the antiproliferative potential of these agents . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CRC cells are known to overexpress IGF 1 receptor ( IGF IR ) , c Met , and uPAR , 3 cell surface receptors known to mediate cell migration and invasion . ^^^ The c Met ribozyme inhibited IGF 1 and HGF mediated migration and invasion , indicating that c Met is essential for these processes . uPA and uPAR inhibition blocked IGF 1 and HGF mediated migration and invasion , suggesting that uPAR is downstream of IGF / IGF IR and HGF / c Met in the signaling pathways that mediate cell migration and invasion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Moreover , GnRH neurons themselves co express IGF 1 and the IGF 1 receptor , and this expression is developmentally regulated . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In May and June , expression of the igf 1 receptor ( igf Ir ) increased 4 to 5 fold , which coincided with an increase in bone density . ^^^ A peak in gh receptor expression is associated with growth activation in Atlantic salmon vertebrae , while upregulation of igf 1 receptor expression is related to increased bone density . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
PURPOSE : Growth factors , particularly insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor ( IGF IR ) in some nonendocrine and a few endocrine tumors , are thought important in recurrence , growth , and aggressiveness . ^^^ EXPERIMENTAL DESIGN : IGF 1 and IGF IR expression in gastrinomas from 54 patients with Zollinger Ellison syndrome were analyzed and correlated with clinical / tumor characteristics . ^^^ IGF 1 and IGF IR mRNA levels were determined by competitive reverse transcription PCR . ^^^ RESULTS : IGF IR mRNA was found in 100 % and IGF 1 in 89 % . ^^^ IGF 1 mRNA expression varied by > 254 fold , IGF IR by 2 , 670 fold , and the levels correlated in a given tumor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The protein levels of ERalpha , IGF 1 Receptor ( IGF IR ) and Bcl 2 were severely reduced , when RU 58 ( R ) 1 cells were cultured with RU 58 , 668 and the expression of progesterone receptor ( PR ) was lost . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , because depletion of beta arrestin 1 almost completely eliminated degradation , and IGF 1 induced down regulation of the receptor in these cells , whereas beta arrestin 2 only had a partial effect , beta arrestin 1 seems to the more important isoform in affecting the expression of IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Many cancers have been shown to overexpress the IGF 1 receptor and produce the ligands ( IGF 1 or IGF 2 ) and some combinations of the six IGF binding proteins . ^^^ With the recent demonstration by epidemiological studies that an elevated serum IGF 1 level is associated with an increased relative risk of developing a number of epithelial cancers , interest has been sparked in this area of research with the possibility of targeting the IGF 1 receptor in cancer treatment protocols . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We demonstrated that the level of IGF 1 and ALS mRNAs is dramatically decreased in both young and aged dwarf livers , transcripts encoding IGF IR and IGFBP 1 are elevated in young dwarfs , but normalize to control levels in aged dwarf livers while transcripts encoding IGFBP 3 are elevated only in aged controls . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , the in vivo effects of estradiol 17beta ( E 2 ) and growth hormone ( GH ) exposure on IGF 1 , IGF 2 , IGF1R , and IGFBP 2 gene expression in sea bream ovary were monitored by RT PCR during prereproductive and reproductive periods . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have suggested that IGF 1 receptor expression , involved in collagen metabolism , may be one of the targets for puromycin induced inhibition of collagen biosynthesis . ^^^ It was found that melanin abolished puromycin induced decrease in the expression of IGF 1 receptor as well MAP kinases expression : ERK 1 and ERK 2 as shown by Western immunoblot analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 , IGF 2 , IGF type 1 receptor ( IGF IR ) , and IGF binding protein ( IGFBP ) 2 and 5 genes was quantified relative to an internal 18S rRNA standard by RT PCR in liver and whole brain tissue on days 14 , 16 , 18 , 20 , 22 , 24 and 26 of embryonic development , as well as at hatch ( H , day 28 ) and at 3 weeks post hatching ( PH ) . ^^^ An inverse relationship was observed for the expression of IGF 1 and IGF IR genes in brain , but not in liver , through 3 weeks PH . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Igfbp 6 is a secreted factor that specifically binds insulin like growth factor 2 ( IGF 2 ) , prevents its binding to the IGF 1 receptor , and is thought to regulate the activity of IGF 2 in growth and differentiation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONTEXT : Mouse knockout models have clearly demonstrated the critical importance of IGF 1 and IGF receptor type 1 ( IGF IR ) for embryonic growth as well as postnatal growth . ^^^ Functions of mutated IGF IR in fibroblasts were evaluated by IGF 1 binding , and IGF 1 stimulated DNA synthesis and beta subunit autophosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Evidence against a direct effect of leptin on insulin like growth factor 1 ( IGF 1 ) , IGFBP 2 and IGF 1 receptor expression in human SK N MC neuroepithelioma cells . ^^^ SK N MC cells were chosen for further investigation since they express IGF 1 , IGF 1 receptor and IGFBP 2 mRNA and secrete IGF 1 and IGFBP 2 protein . ^^^ Secondly and most importantly , when SK N MC cells were cultured in the presence of leptin , neither IGF 1 , nor IGF 1 receptor or IGFBP 2 mRNA expression was different than in the absence of leptin . ^^^ In conclusion , ( 1 ) human SK N MC neuroepithelioma cells express ob and leptin receptor mRNA and secrete leptin . ( 2 ) Added exogenous leptin does not affect IGF 1 , IGFBP 2 or IGF 1 receptor mRNA expression and IGF 1 and IGFBP 2 secretion by SK N MC cells in vitro under the conditions studied . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The biological effects of the IGFs are mediated by the IGF 1 receptor ( IGFR ) , a covalent homodimer composed of two alpha and two beta chains , similar in structure to the insulin receptor ( IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These clonogenic cells and early committed progeny possess a hepatocyte growth factor ( HGF ) c Met and an insulin like growth factor 1 ( IGF 1 ) IGF 1 receptor system that can be activated to induce their migration , proliferation , and survival . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IRS 1 ( Insulin Receptor Substrate 1 ) is an adaptor protein important for insulin and IGF 1 receptor ( Insulin like Growth Factor IR ) transduction to downstream targets . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study investigated the temporal expression and regulation of porcine IGF 1 receptor ( IGF IR ) mRNA and the role of IGF 1 on development of porcine in vitro fertilized ( IVF ) and somatic cell nuclear transfer ( SCNT ) embryos . ^^^ Treating IVF or SCNT embryos with 50 ng / ml IGF 1 significantly up regulated IGF IR mRNA compared to untreated control embryos . ^^^ In conclusion , the present study demonstrated that IGF IR mRNA is expressed in porcine IVF and SCNT embryos , and that IGF 1 improved the developmental competence of IVF and SCNT embryos through its specific receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present study , we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin like growth factor 1 ( IGF 1 ) or antibodies to the IGF 1 receptor ( IGF 1R ) . ^^^ An increase in the expression of the IGF 1R in GHo cells was also detected by Western blot analysis , ( 125 ) 1 IGF 1 binding and analysis of IGF 1R promoter luciferase constructs . ^^^ The results suggest that one of the consequences of the overexpression of GH , in cells lacking the GH receptor , is an increase in the expression of IGF 1 and the IGF 1R which mediate the protection of EL 4 lymphoma cells from apoptosis . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results indicate that IRS 1 ( activated by the IGF 1 receptor ) is one of several proteins that regulate the subcellular localization and activity of beta catenin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study was undertaken to elucidate whether estriol ( E 3 ) affects the proliferative activity and the expression of insulin like growth factor 1 ( IGF 1 ) mRNA and IGF 1 receptor ( IGF IR ) mRNA in cultured human osteoblast like osteosarcoma cells ( HOS TE 85 ) . ^^^ These results demonstrate that E 3 ( 3 . 52 10 10 ( 9 ) , 3 . 52 10 10 ( 8 ) , 3 . 52 10 10 ( 7 ) mol / l ) exerts profound effects on the proliferative potential of cultured HOS TE 85 cells , compatible with that of E 2 ( 3 . 67 10 10 ( 8 ) mol / l ) , through the induction of IGF 1 mRNA expression without affecting IGF IR mRNA expression in these cells . . ^^^ Effects of estriol on proliferative activity and expression of insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor mRNA in cultured human osteoblast like osteosarcoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have developed two bioluminescence resonance energy transfer ( BRET ) based approaches to monitor 1 ) ligand induced conformational changes within partially purified insulin like growth factor 1 ( IGF 1 ) receptors ( IGF1R ) and 2 ) IGF1R interaction with a substrate trapping mutant of protein tyrosine phosphatase 1B ( PTP1B D181A ) in living cells . ^^^ Dose response experiments with IGF 1 , IGF 2 , and insulin demonstrated that the effects of these ligands on BRET correlate well with their known pharmacological properties toward the IGF1R . ^^^ Inhibition of IGF1R autophosphorylation by the tyrphostin AG 1024 ( 3 bromo 5 t butyl 4 hydroxy benzylidenemalonitrile ) resulted in the inhibition of IGF 1 induced BRET signal between the IGF1R and PTP1B . ^^^ In addition , an anti IGF1R antibody known to inhibit the biological effects of IGF 1 inhibited ligand induced BRET signal within the IGF1R , as well as between IGF1R and PTP1B . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : Bromodeoxyuridine DNA incorporation , chemotaxis and the appearance of membrane ruffles were measured in cultured SMCs after incubation with insulin or IGF 1 in the presence of insulin or IGF 1 receptor blocking antibodies . ^^^ On the contrary , insulin induced cell migration was inhibited by blocking the insulin receptor but not the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
As insulin like growth factor 1 ( IGF 1 ) is known for its antiapoptotic effects in different cell types , we investigated whether IGF 1 and its receptor ( IGF IR ) participate in autocrine / paracrine loops affecting the survival of CLL cells . ^^^ Therefore , local production of IGF 1 can account for the increased levels of serum IGF 1 , independently of GH , and may be related to autocrine / paracrine control of lymphocyte survival acting at IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , insulin aspart is equivalent to human insulin on key in vitro parameters such as insulin receptor affinity , insulin receptor dissociation rate , insulin receptor tyrosine kinase activation , IGF 1 receptor binding affinity , metabolic and mitogenic potency . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have suggested that IGF 1 receptor expression , involved in cell growth and collagen metabolism , may be one of the targets for kanamycin induced inhibition of these processes . ^^^ As shown by Western immunoblot analysis melanin augmented kanamycin induced decrease in the expression of IGF 1 receptor as well MAP kinases expression : ERK 1 and ERK 2 . ^^^ The obtained results demonstrate that melanin potentiates the inhibitory effect of kanamycin on IGF 1 receptor dependent signaling pathway in cultured fibroblasts . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Generally , growth hormone promotes local release of insulin like growth factor 1 ( IGF 1 ) , which in turn activates the IGF 1 receptor ( IGF IR ) if present . ^^^ To address this issue , we analyzed phenotypically well characterized primary low passage craniopharyngioma cell lines from nine different patients for IGF IR expression and IGF 1 dependency . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here we report mRNA and protein levels of IGF 1 , the type 1 IGF receptor ( IGF 1R ) and IGF binding proteins ( IGFBP ) 1 , 2 and 3 in fetal gut , liver , muscle and placenta from fetuses in that earlier study in an attempt to explain these contrasting results . mRNA and protein were extracted from tissues obtained at post mortem at 131 days of gestation ( term , 145 days ) from three groups of fetuses ( control , IUGR+saline and IUGR+IGF 1 , n=9 per group ) . ^^^ In liver , muscle and placenta , IGF 1 mRNA and protein levels were reduced by between 8 and 30 % in IGF 1 treated fetuses compared with saline treated fetuses and controls with no change in IGF 1R mRNA or protein levels . ^^^ In contrast , in the gut , IGF 1 mRNA and protein levels were not significantly altered with IGF 1 treatment , but IGF 1R levels were increased , especially in the jejunum . ^^^ Immunolocalisation demonstrated that IGF 1R expression was confined to the luminal aspect of the gut . mRNA levels of all three IGFBPs were reduced in the gut of IGF 1 treated fetuses , but hepatic expression was significantly increased . ^^^ These data demonstrated tissue specific regulation of IGF 1 , IGF 1R and IGFBPs 1 , 2 and 3 in response to intra amniotic IGF 1 supplementation , though the underlying mechanisms remain obscure . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
One of the most important growth factors is IGF 1 , which increases the expression of type 1 and 3 procollagen ( found in the uterus ) ; the IGF 1 receptor is overexpressed in the fibroblasts of keloids . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
At 24 h after UV ( 960 mJ / cm ( 2 ) UVB ) , in comparison to NHKs , HaCaT keratinocytes exhibited significantly higher levels of apoptosis , refractoriness to IGF 1 treatment and reduced IGF IR phosphorylation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These pups also had elevated muscle IGF 1 , IGF 1 receptor , and PPARgamma mRNA levels , which may indicate an attempt to maintain normal insulin sensitivity . ^^^ The increased adiposity and elevated IGF 1 , IGF 1 receptor and PPARgamma mRNAs were not seen in the pups rehabilitated to the balanced diet during lactation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
There is considerable evidence that the epidermal growth factor receptor ( EGFR ) and IGF 1 receptor ( IGF IR ) cross talk in breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Growth factor receptor bound protein ( Grb ) 10 is a protein that interacts with the IGF 1 receptor and may thus regulate IGF 1 stimulated growth . ^^^ Although IGF 1 receptor autophosphorylation normally correlates with receptor signaling , we demonstrate a decrease in IGF 1 stimulated receptor phosphorylation in Grb 10 knockdown cells . ^^^ Pretreatment of cells with the protein tyrosine phosphatase inhibitor pervanadate partially reverses this effect of Grb 10 knockdown on receptor phosphorylation , indicating that endogenous Grb 10 may block phosphatase access to the activated IGF 1 receptor . ^^^ Modulation of the Grb 10 IGF 1 receptor pathway may represent a mechanism that regulates IGF 1 responsive cell and tissue growth . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cell growth stimulated by RSV ( 10 ( 6 ) M ) was blocked by addition of a blocking IGF 1 receptor antibody , or the antiestrogen tamoxifen ( 10 ( 7 ) M ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Postulated mechanisms of action are as follows : ( a ) reduction of levels of circulating IGF 1 , which will decrease activation of the IGF 1 receptor and subsequent signaling pathways ; ( b ) increasing local IGF binding proteins , which may have IGF dependent effects through obstruction of IGF interaction with local IGF 1 receptor as well as IGF independent effects ; and ( c ) interference with estrogens and estrogen receptor action , which may have direct ( and possibly synergistic ) effects on IGF signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In situ hybridization ( ISH ) was used to document the cellular distribution of mRNAs for components of the IGF system ( IGF 1 , IGF 1 receptor [ IGFIR ] and IGF binding proteins [ IGFBP ] 1 to 6 ) in the eyes . ^^^ RESULTS : In nondiabetic rats , mRNA for IGFBP 1 , 5 , and 6 ; IGF 1 ; and IGFIR were detected in the retina . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We examined myocardial expression of insulin like growth factor 1 ( IGF 1 ) , IGF 2 , IGF binding protein 3 ( IGFBP 3 ) , IGF receptor 1 ( IGF 1R ) and IGF 2R in fetal sheep with maternal undernutrition . ^^^ At necropsy on day 78 or day 135 of gestation , gravid uteri were recovered . mRNA expression of IGF 1 and IGF 2 in ventricles were measured with RT PCR , and protein expression of IGF 1R , IGF 2R , IGFBP 3 was quantitated with Western blot . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Strategies targeting the IGF 1 receptor ( IGF 1R ) may therefore be important to develop efficient anti MM agents . ^^^ In vitro data showed that PPP reduced IGF 1R autophosphorylation and downstream ERK activation , leading to inhibition of IGF 1 stimulated proliferation and vascular endothelial growth factor ( VEGF ) secretion of MM cells . ^^^ Inhibiting the IGF 1 receptor tyrosine kinase with the cyclolignan PPP : an in vitro and in vivo study in the 5T33MM mouse model . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibitors of cathepsin B and pro cathepsin B processing , which abolish endosomal proteolysis of IGF 1 and alter tumor cell growth and IGF 1 receptor signalling , merit investigation as antimetastatic drugs . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Skeletal hypothyroidism in TRalpha 1 ( PV ) mutants was accompanied by impaired GH receptor and IGF 1 receptor expression and signaling in the growth plate , whereas GH receptor and IGF 1 receptor expression and signaling were increased in TRbeta ( PV ) mice . ^^^ These data indicate that GH receptor and IGF 1 receptor are physiological targets for T ( 3 ) action in bone in vivo . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , beta cell expression of IGF 1 receptor ( Igf1r ) and insulin receptor ( Insr ) is mandatory for several steps of insulin secretion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When SW 837 cells were treated with EGCG for a longer time , i . e . , 96 h , a very low concentration ( 1 . 0 microg / ml ) of EGCG also caused inhibition of activation of IGF 1R , a decrease in the IGF 1 protein , and an increase in the IGFBP 3 protein . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Clear links between cancer and cellular signaling triggered by the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) and its cognate ligands ( IGF 1 and IGF 2 ) have been reported throughout the past two decades . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study shows that PTEN can partially inhibit the Wnt 1 induced mammary tumorigenesis in early neoplastic stages by blocking the AKT pathway and by reducing the IGF 1 receptor levels in mammary gland . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 induced production of TXB 2 , a metabolite of TXA 2 , was greater in diabetic than in control aortae and was attenuated by endothelium denudation , indomethacin or AG 1024 ( IGF 1 receptor inhibitor ) . ^^^ The expression of the protein and mRNA for the IGF 1 receptor ( as assessed by RT PCR and immunohistochemistry ) was markedly increased within endothelial cells in diabetic aortae but only slightly increased within smooth muscle cells ( versus control rat aortae ) . ^^^ The observed enhancement of IGF 1 receptor expression within endothelial cells may be causally related to the potentiation of vascular contractility and the increase in TXA 2 production . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Phosphorylation of the mammary IGF 1 receptor was increased in the WAP DES mice , but only during prolonged lactation . ^^^ These data support the conclusion that overexpressed des ( 1 3 ) IGF 1 enhanced milk synthesis and mammary development during prolonged lactation through localized and direct activation of the mammary gland IGF 1 receptor and through systemic effects on prolactin secretion and possibly nutrient balance . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Local expression of IGF 1 increased significantly after exercise training by 81 % [ from 6 . 3 ( SE 0 . 8 ) to 11 . 4 ( SE 1 . 4 ) relative units , P=0 . 007 versus control ] while IGF 1 receptor expression was reduced by 33 % [ from 20 . 0 ( SE 2 . 1 ) to 13 . 8 ( SE 1 . 7 ) relative units , P=0 . 008 versus control ] . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 promoted cholangiocyte proliferation in association with overexpression of p IGF1R , IRS 1 , IRS 2 , p ERK1 / 2 and p AKT . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF IR ) has an important role in breast cancer development and progression . ^^^ The WT 1 Wilms ' tumor suppressor gene product interacts with estrogen receptor alpha and regulates IGF 1 receptor gene transcription in breast cancer cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The TbetaR 5 signaling cascade appears to cross talk with the TbetaR I / TbetaR 2 , insulin receptor ( IR ) , IGF 1 receptor ( IGF IR ) , integrin and c Met signaling cascades . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated the changes in IGF 1 clearance , blood glucose and plasma insulin levels , and tissue 2 deoxyglucose uptake after intravenous administration of the IGF aptamer , NBI 31772 , which selectively competes with IGF 1 for binding to the IGFBPs , but has no effect at the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our aim was to characterise the expression and function of IGF 1 receptor ( IGF IR ) and insulin receptor ( IR ) in HCASMCs . ^^^ Phosphorylation of the IGF IR beta subunit was obtained by IGF 1 at 10 ( 10 ) 10 ( 8 ) mol / l and insulin at 10 ( 8 ) mol / l . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We conclude that : 1 ) insulin at physiological concentrations selectively activates IR signaling in bAECs ; 2 ) bAECs express IGF IR and insulin / IGF 1 hybrid receptors in addition to IR ; 3 ) high concentrations of insulin ( > or=1 5 nM ) activate IGF IR and hybrid receptors as well as IR ; and 4 ) this crossover activation can confound interpretation of studies of insulin action in ECs when high insulin concentrations are used . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We have provided evidence that the IGF 1 receptor serves as an anchor for ERalpha in the plasma membrane . ^^^ Estradiol causes phosphorylation of the adaptor protein , Shc and the IGF 1 receptor itself . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Furthermore , IGF 1 receptors ( IGF IR ) were located in and out of membrane lipid rafts and were tyrosine autophosphorylated in response to IGF 1 . ^^^ However , disruption of rafts by acute cholesterol depletion shifted IGF IR to non raft domains , abolished the IGF 1 mediated proapoptotic effect , and inhibited the IGF 1 dependent IRS 1 and Akt recruitment into and phosphorylation / activation within lipid rafts . ^^^ Thus , we propose that segregation of IGF IR in and out of lipid rafts may dynamically regulate the pro and anti apoptotic effects of IGF 1 on apoptosis induced by TNF superfamily members . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
SH EP cells are glial like , express low levels of the type 1 IGF 1 receptor ( IGF IR ) and IRS 2 and high levels of IRS 1 . ^^^ When stimulated with IGF 1 , IRS 1 expression remains constant in SH EP cells ; however , IRS 2 in SH SY5Y cells shows time and concentration dependent degradation , which requires IGF IR activation . ^^^ When SH EP cells are transfected with IGF IR or suppressor of cytokine signaling , IRS 1 is degraded by IGF 1 treatment . ^^^ In summary , 1 ) IRS 2 is more sensitive to IGF 1 mediated degradation ; 2 ) IRS degradation is mediated by phosphatidylinositol 3 kinase and proteasome sensitive pathways ; and 3 ) high levels of IGF IR , and possibly the subsequent increase in Akt phosphorylation , are required for efficient IRS degradation . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We identified the main substrates and signaling pathways [ PI3K / Akt and MAPK ( ERK1 / 2 , p 38 and JNK1 / 2 ] of IGF 1R and investigated the effect of IGF 1 on the stimulation of ovine pituitary cell LH secretion by the various LHRH . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Additional mice were injected with IGF 1 or LR 3 IGF 1 , and phosphorylation of the type 1 IGF receptor ( IGF 1R ) was compared . ^^^ LR 3 IGF 1 stimulated IGF 1R phosphorylation to a greater extent than IGF 1 at both 5 and 10 wk of age ( P < 0 . 01 ) , regardless of gender or genotype ( P > 0 . 21 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Immunoblotting revealed that methyl cyclodextrin had no effect on IGF 1 induced activation of the IGF IR or insulin receptor substrate 1 but increased and decreased the phosphorylation of MAPK and protein kinase B , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The results showed that IGF 1 , IGF IR mRNAs , and phospho insulin receptor substrate 1 ( IRS 1 ) protein were decreased in ECC 1TAM compared with ECC 1E2 tumors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2 / M phase accumulation and apoptosis in multiple myeloma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We show that psychosine inhibits the phosphorylation of Akt and Erk1 / Erk2 ( Erk1 / 2 ) , which are the main anti apoptotic pathways of the IGF 1 receptor ( IGF 1R ) . ^^^ The effects of IGF 1 were dose dependent and resulted in increased IGF 1R autophosphorylation levels . ^^^ Although relatively high concentrations of IGF 1 also resulted in the activation of the insulin receptor ( IR ) , its effect was more significant on the IGF 1R . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Neither CXCR 4 knockdown nor PTX had any effect on the ability of IGF 1 to activate IGF 1R , suggesting that CXCR 4 and G proteins are activated subsequent to , or independently of , phosphorylation of IGF 1R by IGF 1 . ^^^ Coprecipitation studies revealed the presence of a constitutive complex containing IGF 1R , CXCR 4 , and the G protein subunits , G ( 1 ) alpha 2 and Gbeta , and stimulation of MDA MB 231 cells with IGF 1 led to the release of G ( 1 ) alpha 2 and Gbeta from CXCR 4 . ^^^ Based on our findings , we propose that CXCR 4 constitutively forms a complex with IGF 1R in MDA MB 231 cells , and that this interaction allows IGF 1 to activate migrational signaling pathways through CXCR 4 , G ( 1 ) alpha 2 and Gbeta . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , overexpression and / or constitutive activation of the IGF 1 receptor ( IGF IR ) or different components of the IGF IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transcripts of the IGF 1 receptor ( r ) and IGF binding protein ( BP ) 2 were detected in all embryos , regardless of origin . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Similarly , elevated expressions of the steady state mRNA of IGF 1 , IGF IR , and Cox vb were observed on day 4 in animals with the ovaries intact and these expressions were enhanced by E 2 treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Endometrial IGF gene and protein expression , IGF 1 receptor ( IGF IR ) gene expression , and uterine lumenal content of IGF binding proteins ( IGFBPs ) were evaluated in control and oestrogen treated gilts on Days 10 , 12 , 13 , 15 and 17 of gestation . ^^^ Oestrogen treatment altered endometrial IGF 1 and IGF IR gene expression on Days 12 and 13 of gestation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In breast cancer , we have previously shown that insulin like growth factor 1 ( IGF 1 ) enhances cell motility in the highly metastatic MDA 231BO cell line by activating the type 1 IGF receptor ( IGF1R ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Occupation of alphavbeta 3 integrin by endogenous ligands modulates IGF 1 receptor activation and proliferation of human intestinal smooth muscle . ^^^ The aim of the present study was to determine whether occupation of the alpha ( 5 ) beta ( 3 ) receptor influences IGF 1 receptor tyrosine kinase activation and function in human intestinal smooth muscle cells . ^^^ In the presence of the alpha ( 5 ) beta ( 3 ) ligand fibronectin , IGF 1 stimulated IGF 1 receptor activation was augmented . ^^^ Conversely , in the presence of the alpha ( 5 ) beta ( 3 ) specific disintegrin echistatin , IGF 1 stimulated IGF 1 receptor tyrosine kinase phosphorylation was inhibited . ^^^ IGF 1 stimulated IGF 1 receptor activation was accompanied by recruitment of the adapter protein IRS 1 , activation of Erk1 / 2 , p70S6 kinase , and proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
With regard to the regulation of survival pathway , using dot blotting , we found cardiac insulin like growth factor 1 ( IGF 1 ) and IGF 1 receptor mRNA levels to be significantly increased , indicating that compensative effects of IGF 1 survival signaling could occur . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of a peptide IGF 1 receptor antagonist ( JB 3 ) has been examined on kidney fibrosis and function in the rat following 5 / 6 subtotal nephrectomy ( SNx ) . ^^^ Thus an interventional study with an IGF 1 receptor antagonist does not support a role for IGF 1 in the development of renal fibrosis in the SNx rat , although IGF 1 does make an important contribution to compensatory kidney growth . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Intravenous IGF 1 receptor antisense reduces IGF IR expression and diminishes pressor responses to angiotensin 2 in conscious normotensive rats . ^^^ Given the variety of cardiovascular effects of insulin like growth factor 1 ( IGF 1 ) , we investigated the effects of a functional deficit in IGF 1 signalling in the conscious rat cardiovascular system using intravenous IGF 1 receptor antisense ( AS , 0 . 5 nmol ) treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibition of insulin / IGF 1 receptor signaling enhances bile acid toxicity in primary hepatocytes . ^^^ Herein , we extend our analyses to examine the impact of insulin / IGF 1 receptor inhibition on primary hepatocyte survival when exposed to the secondary bile acid deoxycholic acid ( DCA ) and compare the impact inhibition of this receptor has on bile acid toxicity effects to that of ERBB1 / MEK1 / 2 inhibition . ^^^ The insulin / IGF 1 receptor inhibitor NVP ADW 742 at concentrations which inhibit both the insulin and IGF 1 receptors had a modest negative impact on hepatocyte viability , and strongly potentiated DCA induced apoptotic cell death . ^^^ Identical data were obtained expressing a dominant negative IGF 1 receptor in hepatocytes ; a receptor which acts to inhibit both the IGF 1 receptor and the insulin receptor in trans . ^^^ Inhibition of ERBB 1 function using Iressa ( gefitinib ) or the tyrphostin AG 1478 had more modest effects at enhancing DCA lethality than inhibition of the insulin / IGF 1 receptor function . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Secreted IGFBP 3 neutralized IGFs and prevented IGF 1 receptor ( IGF IR ) activation . ^^^ When stably overexpressed , wild type IGFBP 3 but not I56G / L80G / L81G ( GGG ) mutant IGFBP 3 , which has a reduced affinity to IGFs , prevented IGF 1 from activating IGF IR and Akt as well as stimulating cell proliferation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Cyclic stretch increased , while SB 203580 , IGF 1 , and IGF 1 receptor antibody abolished , the phosphorylated p 38 protein . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Blockade of IGF 1 receptor function prevented rapamycin ' s activation of AKT . ^^^ Thus , mTOR inhibitors activate PI 3 K / AKT in multiple myeloma cells ; activation depends on basal IGF R signaling ; and enhanced IRS 1 / IGF 1 receptor interactions secondary to inhibited IRS 1 serine phosphorylation may play a role in activation of the cascade . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These results suggest that IGF 1 treatment prevents motor neuron loss by affecting the signal transduction system through IGF 1R and the main downstream signal , IRS 1 . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
P2Y12 receptor signalling towards PKB proceeds through IGF 1 receptor cross talk and requires activation of Src , Pyk 2 and Rap 1 . ^^^ Although the increased PKB phosphorylation was abolished in the presence of the IGF 1 receptor tyrosine kinase inhibitor AG 1024 , 2MeSADP did not significantly increase receptor phosphorylation . ^^^ Nevertheless , phosphorylation of a 120 kDa IGF 1 receptor associated protein was observed . ^^^ Consistent with the signalling towards Rap 1 and PKB , activation of Pyk 2 was abrogated by Ca2+ chelation , inhibition of PLD 2 and IGF 1 receptor tyrosine kinase activity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In prostate cancer cells proliferation is regulated by modulation of the IGF 1 receptor ( IGF R 1 ) by the androgen receptor ( AR ) and its co activator prostate derived Ets factor ( PDEF ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Thus , cardiomyocytes derived from human ES cells proliferate extensively in vitro , and their proliferation appears to be mediated primarily via the PI 3 kinase / Akt signaling pathway , using the IGF 1 receptor as one upstream activator . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We studied expression of the ligands IGF 1 and IGF 2 , the inhibitory IGF binding protein 3 , the type 1 IGF receptor ( IGF IR ) , and the downstream mediator insulin receptor substrate 1 by immunohistochemistry in 56 tissue specimens ( 28 low grade and 28 high grade prostate adenocarcinomas ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Sections were processed for in situ hybridization and immunohistochemistry . mRNA and protein expression profiles IGF 1 , IGF 2 , IGF IR , and IGF IIR mRNA were essentially identical . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF system is a complex network comprised of two growth factors ( IGF 1 and 2 ) , cell surface receptors ( IGF IR and IIR ) , six specific high affinity binding proteins ( IGFBP 1 to IGFBP 6 ) , IGFBP proteases as well as several other IGFBP interacting molecules , which regulate and propagate IGF actions in several tissues . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We now present evidence that blockade of the IGF 1 receptor in the choroid plexus originates changes in brain that are reminiscent of those found in AD . ^^^ In rodents , IGF 1 receptor impairment led to brain amyloidosis , cognitive disturbance , and hyperphosphorylated tau deposits together with other changes found in Alzheimer ' s disease such as gliosis and synaptic protein loss . ^^^ While these disturbances were mostly corrected by restoring receptor function , blockade of the IGF 1 receptor exacerbated AD like pathology in old mutant mice already affected of brain amyloidosis and cognitive derangement . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
When cells carrying the antisense IGF IR expression construct were exposed to IGF 1 , tPA protein accumulation was significantly lower than that of control transfected cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNA expression of IGF 1 , IGF 2 , and IGF 1 receptor ( IGF 1R ) increased during injury . ^^^ The addition of anti IGF 1R and anti IGF 1 antibodies inhibited the cell proliferation and trans differentiation to some extent , as evident by cell morphology and the expression of type 1 and type 2 cell markers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
RESULTS : The OVCAR 3 and OVCAR 4 cell lines produce IGF 1 and IGF 2 , and express IGF IR , detectable by Western blotting , supporting the existence of an autocrine loop . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF I / IGF 1 receptor pathway : Implications in the Pathophysiology of Thyroid Cancer . ^^^ The biological actions of the insulin like growth factor ( IGF ) 1 are mediated by its activation of the IGF 1 receptor ( IGF 1 R ) , a transmembrane tyrosine kinase linked to the Akt and ras raf MAPK cascades . ^^^ We have previously documented increased IGF 1 and IGF 1 receptor immunoreactivity in human thyroid carcinomas with a corresponding up regulation of IGF 1 mRNA . ^^^ Immunoreactivity for IGF 1 and IGF 1 receptor positively correlated with tumor diameter , but not with the occurrence of lymph node metastases . ^^^ Several recent studies have identified new signaling pathways emanating from the IGF 1 receptor that affect cancer cell proliferation , adhesion , migration and apoptosis , which represent critical functions for cancer cell survival and metastasizing capacity . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF binding proteins ( IGFBPs ) represent a class of natural IGF antagonists that bind to and sequester IGF 1 / 2 from the IGF 1R , making them attractive candidates as therapeutics for cancer prevention and control . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We measured insulin stimulated phosphorylation of the IR and IRS 1 , IRS 1 p 85 association and Akt activation , and the abundance of the IR , IRS 1 , p 85 , GLUT 4 and IGF 1 receptor in skeletal muscle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Individuals underwent biopsy of the right vastus lateralis muscle , and real time polymerase chain reaction ( PCR ) amplification of mRNAs for insulin like growth factor 1 ( IGF 1 ) , IGF 2 , IGF 1 receptor ( IGF IR ) , IGF IIR , and myostatin ( 44 patients ) was performed . ^^^ Skeletal muscle mRNA for IGF IEa , IGF 2 , and IGF 1 receptor is decreased in sedentary chronic hemodialysis patients . ^^^ CONCLUSION : In sedentary , clinically stable maintenance hemodialysis patients as compared to sedentary normal individuals , the mRNA levels for IGF IEa , IGF 2 , and the IGF 1 receptor are decreased in vastus lateralis muscle . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To study whether this inhibitory effect in cells was due to a direct action on these receptors , we studied the IGF 1 stimulated tyrosine kinase activity of isolated IGF 1R , which was inhibited by NDGA at 10 muM or less . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The mRNA of IGF 1 and IGF type 1 receptor ( IGF 1R ) , as well as IGF 1R binding capacity were unaffected by butyric acid treatments . ^^^ The abundance of IGF 1 mRNA tended to be lower ( p = 0 . 1 ) and IGF 1R abundance was lower ( p = 0 . 03 ) in response to the HL . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Increased expression of the IGF 1 receptor ( IGF IR ) is associated with proliferation and survival of vascular smooth muscle cells ( VSMCs ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The occurrence of cross talk between IGF IR and HER 2 exclusively in resistant cells is evidenced by the IGF 1 stimulation resulting in increased phosphorylation of HER 2 in resistant cells , but not in parental cells , and by the inhibition of IGF IR tyrosine kinase activity leading to decreased HER 2 phosphorylation only in resistant cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor and insulin receptor substrate 2 levels were increased in LTED versus the Wt MCF 7 cells , and ICI but not TAM reduced their expression in a dose dependent fashion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
An experiment was carried out to determine the pattern of follicular expression of mRNAs for aromatase , IGF 1 receptor ( IGF IR ) , IGF binding protein ( IGFBP ) 2 , 4 and 5 , leptin and the long form of the leptin receptor ( Ob Rb ) in ten ewes infused with human recombinant leptin ( n = 5 ; 1 microg / h ) or saline ( n = 5 ) for 72 h in the luteal phase of the oestrous cycle . ^^^ The ovarian expression of mRNAs for aromatase , IGF 1 receptor , IGF binding protein 2 , 4 and 5 , leptin and leptin receptor in cycling ewes after three days of leptin infusion . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 is a potent survival factor for human vascular smooth muscle cells ( hVSMC ) , and its antiapoptotic effects are mediated via the IGF 1 receptor ( IGF 1R ) through a signaling pathway involving phosphatidylinositol 3 kinase and Akt . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In H9c2 cells , coincubation with PMA lead to an increase in the rate of the IGF 1 receptor activation , and this may further implicate a role for PKC in regulating the IGF1R . ^^^ In conclusion , PKC alpha plays an essential role in the IGF 1 signaling cascade , including the regulation of key signaling proteins involved in cell signaling and gene expression , and this may primarily be due to PKC alpha directly regulating the IGF1R . . ^^^ PKC alpha dependent regulation of the IGF 1 receptor in adult and embryonic rat cardiomyocytes . ^^^ In both , the adult rat ventricular cardiomyocytes and the embryonic rat heart cell line , H9c2 , acute exposure to IGF 1 resulted in activation of the IGF 1 receptor ' s internal tyrosine kinase , and this was completely blocked by the PKC alpha inhibitor , G6976 . ^^^ In addition , RNA interference using siRNA mediated gene silencing of PKC alpha inhibited IGF 1 receptor activity and blocked PKC alpha expression in H9c2 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism ( StAR , CYP 11 , CYP 17 , CYP 19 HSD17B1 3 , HSD3B1 2 ) , gonadotropin and gonadal hormones action ( ACTR 1 , ACTR2A B , FS , INHA , INHBA B , INHC , SHBG , LHCGR , FSHR , MADH 4 , AR ) , obesity and energy regulation ( MC4R , OB , OBR , POMC , UCP 2 3 ) , insulin secretion and action ( IGF 1 , IGF1R , IGFBPI 1 3 , INS VNTR , IR , INSL , IRS 1 2 , PPARG ) and many others . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Treatment with an anti human IGF neutralizing monoclonal antibody , KM 1468 , inhibited the IGF 1 stimulated phosphorylation of type 1 IGF receptors ( IGF IR ) in RPMI 8226 cells and the activation of the downstream PI 3 K / Akt signaling pathway in vitro . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We therefore examined the beta cell phenotype in the MKR mouse , a model in which expression of a dominant negative IGF 1 receptor ( IGF1R ) in skeletal muscle leads to systemic insulin resistance and diabetes . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , Akt 1 down regulation in IGF IR stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial mesenchymal transition ( EMT ) and enhanced cell migration induced by IGF 1 or EGF stimulation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated the actions of DHT , T , DHEA , and estradiol ( E 2 ) on insulin like growth factor ( IGF ) 1 , IGF 2 , IGF 1 receptor ( R ) , IGF binding protein ( IGFBP ) 2 , IGFBP 3 , and IGFBP 5 in primary cultures of human prostatic stromal cells by assessing cell proliferation , mRNA expression , and protein secretion by MTT growth assay , quantitative real time PCR , and ELISA , respectively . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The cellular responses to the IGFs are mediated primarily by the IGF 1 receptor . ^^^ The IGF 1 receptor is a member of the family of tyrosine kinase growth factor receptors , and is highly homologous ( 70 % ) to the insulin receptor , especially in the tyrosine kinase domain ( 84 % ) ADDIN . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Because genistein has previously been reported to decrease HT 29 cell growth , the present study compared the effects of genistein with daidzein on the protein levels of the members of the ErbB receptor family and insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) . ^^^ Immunoprecipitation / western blot analyses revealed that genistein decreased IGF 1 stimulated phosphorylation of IGF IR and IRS 1 , recruitment of p 85 to IGF IR , and phosphorylation of Akt . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We hypothesized that scintigraphic detection of MYC or CCND 1 peptide nucleic acid ( PNA ) probes with an IGF 1 peptide loop on the C terminus , and a Tc 99m chelator peptide on the N terminus , could measure levels of MYC or CCND 1 mRNA noninvasively in human IGF1R overexpressing MCF 7 breast cancer xenografts in immunocompromised mice . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This study is to investigate the regulatory mechanism of IGF 1 receptor ( IGF 1R ) signaling and its importance in cervical cancer formation . ^^^ IGF 1 stimulated invasion and proliferation were abolished by functional blocking monoclonal antibody against IGF 1R , whereas these cellular functions were unaffected by either IgG or monoclonal antibody to insulin receptor . ^^^ Functional blocking monoclonal antibody against integrins alpha ( 5 ) beta 3 , but not alpha 2 alpha3 , alpha 4 alpha6 beta 1 , beta 4 or alpha2beta1 , inhibited the IGF 1 stimulated invasion and proliferation in cervical cancer cells . alpha ( 5 ) beta 3 integrin modulated IGF 1R phosphorylation by altering the rate of Src homology 2 containing phosphotyrosine phosphatase ( SHP 2 ) recruitment to the activated IGF 1R . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 receptor ( IGF IR ) is a newly recognized self antigen that , when activated in GD fibroblasts by IGF 1 or GD IgGs , provokes the expression of IL 16 and RANTES ( regulated upon activation , normal T cell expressed and secreted ) dependent T lymphocyte chemoattraction and hyaluronan synthesis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since R type channels exist in NET cells and couple to both , IGF 1 receptor signaling as well as CgA secretion , pharmacological interference with R type channels may represent a new therapeutic option by blocking Ca ( 2+ ) signaling thereby abrogating IGF 1 dependent hypersecretion in NET disease . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
They bound with high ( subnanomolar ) affinity to IGF 2 , did not cross react with IGF 1 and insulin , and potently inhibited signal transduction mediated by the IGF IR interaction with IGF 2 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) and its receptor ( IGF IR ) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells , retinal pigment epithelial cells , Mller cells and endothelial cells . ^^^ Proliferating endothelial cell specific expression of IGF 1 receptor ribozyme inhibits retinal neovascularization . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Expression of IGF 1 , IGF 2 , and IGF IR in gallbladder carcinoma . ^^^ This study was designed to analyse the expression of the IGF 1 receptor ( IGF IR ) and its ligands ( IGF 1 , IGF 2 ) in gallbladder cancer . ^^^ METHODS : IGF 1 , IGF 2 , and IGF IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node ( n = 11 ) and hepatic ( n = 7 ) metastases using a tissue microarray technique and correlated with tumour stage , grade , and patient outcome . ^^^ RESULTS : Cancer tissue allowing a reliable evaluation of IGF 1 , IGF 2 , and IGF IR was present in 55 of 57 primary tumours and 17 of 18 metastases . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Evidence from in vitro and animal studies suggests that members of the insulin like growth factors ( IGFs ) system , including IGF 1 , IGF 2 , the IGF 1 receptor ( IGF IR ) , and the IGF binding proteins ( IGFBPs ) play a central role in the development and progression of cancer . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
After 6 months , many altered liver acini progressed to other types of preneoplasias often accompanied by an overexpression of the glutathione S transferase ( placental form ) , IGF 1 receptor , and transforming growth factor ( TGF ) alpha . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Inhibition of CCN 6 expression promoted anchorage independent growth of HME cells and rendered them more responsive to the growth effects of IGF 1 , which was coupled with the increased phosphorylation of IGF 1 receptor and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Defects in IGF 1 receptor associated signaling has , however , been shown to significantly extend lifespan in models ranging from invertebrates to mouse . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We found that IGF 1 promotes the migratory capacity of androgen independent prostate cancer cells through the activation of its specific receptor , IGF IR . ^^^ This study : a ) supports a crucial role for IGF 1 in the progression of the pathology towards the highly metastatic phase ; and b ) provides an additional rationale basis for the development of therapeutic strategies directed at the IGF I / IGF IR system in the treatment of androgen independent prostate cancer . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The IGF 1 and IGF 1R expression in pairs of breast cancer tissue and ANCT were investigated using RT PCR and immunohistochemistry . ^^^ MATERIALS AND METHODS : IGF 1 and IGF 1R mRNA from 31 specimen pairs were estimated using RT PCR . ^^^ There was no difference in the expression of the IGF 1 receptor in both types of tissue , as proven by RT PCR and immunohistochemistty . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Compared with group M , piglets in group MI exhibited significantly increased expression levels of both insulin and GH receptor in the ileum , and LAP in the jejunum ( p < 0 . 05 ) ; IGF 1 receptor expression levels in both the jejunum and ileum were significantly decreased ( p < 0 . 01 and p < 0 . 05 , respectively ) , while IGF 1 expression was unchanged ( p > 0 . 05 ) . ^^^ Dietary insulin suppressed IGF 1 receptor expression , which may be the result of negative feedback caused when insulin binds to IGF 1 receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In these cells , the type 1 insulin like growth factor ( IGF 1 ) and granulocytic colony stimulating factor ( G CSF ) induce differentiation to granulocytes . 32D cells do not express insulin receptor substrate 1 ( IRS 1 ) or IRS 2 , docking proteins of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Neuroprotective effects of activated protein C through induction of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor , and its downstream signal phosphorylated serine threonine kinase after spinal cord ischemia in rabbits . ^^^ To investigate the mechanisms by which APC prevents ischemic spinal cord damage , we performed immunoreactivity and Western blotting of insulin like growth factor 1 ( IGF 1 ) , IGF 1 receptor , and phosphorylated serine threonine kinase ( p Akt ) . ^^^ Induction of IGF 1 receptor and the downstream factor p Akt was stronger and more prolonged in group A . ^^^ CONCLUSIONS : These results indicate that induction of IGF 1 , IGF 1 receptor , and p Akt might partially explain the neuroprotective effects of APC after transient spinal cord ischemia in rabbit . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin like growth factor 1 ( IGF 1 ) , IGF 2 , and insulin have all been implicated in regulating several aspects of the malignant phenotype via the type 1 IGF receptor ( IGF1R ) and insulin receptor ( IR ) . ^^^ We have previously shown that a chimeric single chain antibody against IGF1R ( scFv Fc ) and a murine antibody EM 164 down regulate IGF1R , making breast cancer cells unresponsive to IGF 1 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
For migration inhibition assays , HCECs were pretreated with inhibitors of the IGF 1 receptor ( alphaIR 3 ) , the PI 3 K / AKT pathway ( LY 294002 ) , and the MEK ERK pathway ( PD 98059 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Muscle IGF 1 receptor ( IGF IR ) lysine arginine ( MKR ) mice expressing dominant negative mutant IGF IRs in skeletal muscle are diabetic with insulin resistance in muscle , liver , and adipose tissue . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We hypothesized a cortisol induced upregulation of fetal hepatic GH receptor ( GH R ) mRNA levels , secondary increases in IGF 1 mRNA levels , and circulating IGF 1 levels , but a downregulation of the type 1 IGF receptor ( IGF IR ) as an explanation . ^^^ However , in liver , GH R , but not IGF 1 or IGF IR , mRNA levels were decreased in both IUGR groups . ^^^ In contrast , in placenta , GH R , IGF 1 , and IGF IR expression were increased in IUGR vehicle infused fetuses . ^^^ GH infusion further increased placental GH R and IGF IR , but abolished the increase in IGF 1 mRNA levels . ^^^ GH infusion reduced IGF 1 expression in muscle and increased GH R but decreased IGF IR expression in kidney . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Interaction with the IGF 1 receptor , DNA synthesis , and intracellular signal transduction were assessed in cardiac K 6 myoblasts . ^^^ IGF 1 receptor binding affinity was lower ( four to fivefold ) for glulisine , but significantly higher ( four fold ) for Asp ( B 10 ) versus RHI . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study aims to investigate the effect of IGF 1 receptor ( IGF IR ) gene activation on the expression of monocarboxylic acid transporters ( MCTs ) in hepatocarcinoma cells . ^^^ Furthermore , the cellular uptake of benzoic acid , a representative substrate of MCT 1 , was significantly ( p < 0 . 05 ) enhanced following the activation of IGF IR via the pre incubation with IGF 1 ( 10 ng / ml ) . ^^^ IGF 1 receptor gene activation enhanced the expression of monocarboxylic acid transporter 1 in hepatocarcinoma cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
METHODS : Expression of insulin receptor , IGF 1 receptor , and SCF was studied in gastric muscles and purified ICC by immunohistochemistry and reverse transcription polymerase chain reaction ( RT PCR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Since insulin like growth factor 1 ( IGF 1 ) is the most potent stimulator of collagen biosynthesis in fibroblasts , the effect of butyrate on IGF 1 receptor ( IGF IR ) expression was evaluated . ^^^ Butyrate induced collagen biosynthesis in cultured fibroblasts is independent on alpha2beta1 integrin signalling and undergoes through IGF 1 receptor cascade . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Binding analysis indicated that IGF binding proteins ( IGFBPs ) , primarily localized with the extracellular matrix , were the primary IGF 1 binding elements in our system , with twice as many binding sites ( 8 . 0 + / 1 . 9 10 10 ( 4 ) per cell ) as IGF 1 receptors ( IGF IR ) ( 3 . 9 + / 0 . 6 10 10 ( 4 ) per cell ) . ^^^ Internalization of IGF 1 by IGF IR , but not IGFBPs , was detected , however both receptor and IGFBP binding were shown to inhibit rather than enhance the transport of intact IGF 1 , albeit in different ways . ^^^ IGFBPs retained IGF 1 in the apical region while IGF IR binding led to protein degradation . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To test the hypothesis that there may be an altered regulation of p 16 in psoriatic involved skin , we have measured genes involved in the Igf 1 receptor signalling through the Ras / MAPK cascade . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , IGF 1 , IGF 1 receptor , and IRS 1 protein levels were induced by exposure to 25 mm glucose in both cell lines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONTEXT : Signaling via the IGF 1 receptor ( IGF IR ) is crucial for normal prenatal and postnatal growth . ^^^ CONCLUSIONS : In vivo and in vitro IGF 1 resistance in Arg59Ter subjects and fibroblasts indicates a human IGF1R gene dosage effect involving not only the IGF IR , but also IGF IR / IR hybrids . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The FITC insulin distribution was compared with that of insulin receptors ( IR ) , IGF 1 receptors ( IGF IR ) , and caveolin 1 ( a protein marker for caveolae ) in skeletal muscle vasculature . ^^^ Finally , the ability of insulin , IGF 1 , and IGF 1 blocking antibody to diminish insulin transport across bAECs grown on transwell plates suggested that IGF IR , in addition to IR , can also mediate transendothelial insulin transit . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Biochemical evidence that SOCS 2 binds to the IGF 1 receptor ( IGF IR ) supports the novel possibility that SOCS 2 limits IGF 1 action . ^^^ The current study tested the hypothesis that SOCS 2 normally limits basal or IGF 1 induced intestinal growth and limits IGF IR signaling in intestinal epithelial cells . ^^^ IGF 1 stimulated activation of IGF IR and downstream signaling intermediates were enhanced in the intestine of SOCS 2 null mice and were decreased by SOCS 2 overexpression in Caco 2 cells . ^^^ We conclude that SOCS 2 normally limits basal and IGF 1 and EGF induced intestinal growth in vivo and has novel inhibitory effects on the IGF IR tyrosine kinase pathway in intestinal epithelial cells . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The present study has the following aims : ( 1 ) Since high doses of insulin , as found in MDI , will activate the IGF 1 receptor , we sought to determine if IGF 1 is capable of reproducing the lipogenic effect seen with MDI treatment , and ( 2 ) to determine if the sterol response element binding protein 1 ( SREBP 1 ) pathway mediates the increase in lipogenesis . ^^^ These data indicate that activation of the IGF 1 receptor increases lipogenesis in SEB 1 cells through both SREBP dependent and SREBP independent pathways . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Transgenic mice expressing a constitutively active IGFIR or IGF 1 develop mammary tumors and increased levels of IGFIR have been detected in primary breast cancers . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In order to determine the role of the IGF 1 receptor ( IGF IR ) in human pheochromocytomas we have compared the expression of the IGF IR in normal tissues and in pheochromocytomas with regard to the IGF IR mRNA levels and ligand binding . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here , we studied the anti neoplastic effects of an inhibition of the IGF 1 receptor ( IGF 1R ) signalling in NET cells by the novel IGF 1R tyrosine kinase ( TK ) inhibitor NVP AEW 541 , whose anti neoplastic potency has not yet been tested in NET disease . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Disruption of the IGF 1 , IGF 2 or IGF1R gene retards fetal growth , whereas disruption of IGF2R or overexpression of IGF 2 enhances fetal growth . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expression of phosphorylated EGF receptor ( p EGFR ) , IGF 1 receptor alpha subunit ( IGF IRalpha ) and phosphorylated TGFbeta receptor type 2 ( p TGFbeta RII ) was assessed by Western blot analysis . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Recent published research on the actions of IGF 1 in humans and the phenotypes of children with genetic defects in the GH / IGF axis establish IGF 1 signaling via its receptor ( IGF IR ) as the critical growth controlling element in man . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To further investigate the IGF 1 receptor signaling pathways that are required for the permissive effect of the receptor on transformation by SV 40 T antigen , we established three independent fibroblast cell lines each from wild type and IGF 1 receptor null embryos ( R ) . ^^^ We conclude that late passage IGF 1 receptor null mouse embryo fibroblasts can be transformed by SV 40 T antigen , and that ErbB 3 may play a role in permitting transformation by T antigen . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Prostate cancer shows high expression of type 1 insulin like growth factor ( IGF 1 ) receptor ( IGF IR ) and prostate stromal cells ( PrSC ) produce IGF 1 . ^^^ The conditioned medium of PrSC , as well as IGF 1 , induced phosphorylation of IGF IR and increased the growth of LNCaP and DU 145 cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In the present work , we aimed to elucidate a possible interaction between PDGF receptor ( PDGFR ) and IGF 1 receptor ( IGF IR ) signaling in LMFs . ^^^ IGF 1 and PDGF BB differentially affected IGF IR and PDGFR signaling . ^^^ High concentrations of IGF 1 decreased levels of IGF IR and IRS 1 and inhibited the expression and activation of PDGFRalpha . ^^^ PDGF BB prevented IGF 1 induced downregulation of the IGF IR , but did not affect expression of its cognate receptor subunits . ^^^ In conclusion , the presented data demonstrate that the PDGFR signaling requires a functional IGF IR and that PDGF BB stabilizes the IGF IR function through preventing the IGF 1 induced downregulation of the IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Exposure to insulin like growth factor 1 ( IGF 1 ) of human lung adenocarcinoma cell lines ( A 549 and H 1299 ) triggers IGF IR ubiquitination and internalization processes that require energy and are preceded by the phosphorylation of receptor tyrosines . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This review summarizes our current understanding of how IGF 1 receptor signaling interferes with the apoptotic machinery of the cell . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Unlike the liver , which is mostly unaffected by changes in IGF 1 level , skeletal muscles express high levels of IGF 1 receptor ( IGF IR ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
These abnormalities were associated reduced expression of genes encoding insulin , IGF 2 , insulin receptor , IGF 1 receptor , and insulin receptor substrate 1 , and reduced ligand binding to the insulin and IGF 2 receptors . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
However , PTH increased the mRNA levels of IGF 1 and IGF IR only in the bones of male mice . ^^^ These differences between male and female mice may reflect the greater response to PTH of IGF 1 and IGF IR gene expression in males enhancing the anabolic effect on cortical bone . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The exact molecular mechanisms are unclear but may involve the modulation of hepatic and muscle insulin sensitivity , possibly by altering insulin and IGF 1 receptor responsiveness and / or density . . ^^^
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Decalcified and paraffin embedded TMJs of 48 NMRI mice sacrificed in groups of three male and females each at the ages of 3 , 4 , 5 , 7 , 9 , 10 , 12 , and 18 months were prepared for histopathology and immunohistochemistry for IGF 1 and 2 , IGF 1 receptor and IGF binding proteins 1 , 2 , 3 , 4 , 5 , and 6 . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To evaluate the role of IGF2R or IGFBPs in mediating the actions of RA , the IGF 2 analogs [ Leu 27 ] IGF 2 ( 10 20 fold reduced IGF 1 receptor affinity ) and des ( 1 6 ) IGF 2 ( lower IGFBP binding affinity ) were used . ^^^ CONCLUSIONS : These data implicate a novel antiproliferative role for RA in enhancing the pericellular clearance of IGF 2 via the IGF2R preventing ligand activation of the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Our findings confirm previous studies indicating that IGF F 1 1 is a weak antagonist of IGF 1 binding to the IGFBPs and the IGF 1R and suggest that it does not effectively inhibit downstream events stimulated by IGF 1 . ^^^ IGF F 1 1 may act in conjunction with IGF 1 at the IGF 1R or independently of IGF 1 at the IGF 1R or another receptor . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This dissociation of PP2A from RACK 1 and an IGF 1 mediated decrease in cellular PP2A activity did not occur in cells expressing either the serine 1248 or tyrosine 1250 / 1251 mutants of the IGF IR that do not interact with RACK 1 . ^^^ Taken together , our findings indicate that RACK 1 enhances IGF 1 mediated cell migration through its ability to exclusively associate with either beta 1 integrin or PP2A in a complex at the IGF IR . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The effect of rhIGF 1 treatment was evaluated in a mouse model of type 2 DM ( MKR mouse ) , which expresses a dominant negative form of the human IGF 1 receptor under the control of the muscle creatine kinase promoter specifically in skeletal muscle . ^^^ Also , these results suggest that a functional IGF 1 receptor in skeletal muscle is required for IGF 1 to improve insulin sensitivity in this mouse model of type 2 DM . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
H 89 abolished the adverse effects of acidosis on condylar development and restored IGF 1 and IGF 1 receptors ( IGF IR ) levels . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor antisense treatment caused a significant decrease in pressor responses to angiotensin 2 in comparison with full length mismatch treatment ( E ( max ) was reduced to 65 + / 7 mm Hg compared with 99 + / 6 mm Hg , p < 0 . 05 ) . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We studied the signalling properties of AspB 10 insulin , an analog with enhanced affinity for the IGF 1 receptor , in comparison to native insulin using primary human skeletal muscle cells . ^^^ Phosphorylation of IRS 1 in response to insulin was inhibited equally by blocking either the insulin or the IGF 1 receptor . ^^^ IRS 1 activation by AspB 10 insulin was only inhibited by blocking the IGF 1 receptor . ^^^ IRS 2 phosphorylation induced by both insulin and AspB 10 insulin was nearly insensitive to blocking the insulin receptor , being predominantly mediated by the IGF 1 receptor . ^^^ We conclude that in myoblasts IRS 2 , but not IRS 1 , functions as preferred substrate for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
CONTEXT : The type 1 IGF 1 receptor ( IGF1R ) mediates the biological functions of IGF 1 . ^^^ Binding of IGF 1 to the IGF1R results in autophosphorylation of the intracellular beta subunit and activation of intracellular signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The type 1 insulin like growth factor receptor ( IGF 1R ) is the cognate tyrosine kinase receptor for the insulin like growth factor IGF 1 and is expressed widely in many foetal and postnatal tissue cells . ^^^ Designing antagonists for IGF 1R would be greatly facilitated by the availability of structural information on the complex between IGF 1 and IGF 1R . ^^^ In the present work we model the three dimensional structure of the complex between IGF 1 and the first three domains of IGF 1R using a macromolecular docking method guided by selected experimental data . ^^^ Model for the complex between the insulin like growth factor 1 and its receptor : towards designing antagonists for the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In addition , 1 pig from each pen in Experiments 1 and 2 was selected randomly to obtain the small intestinal mucosa for analyzing IGF 1 and IGF 1 receptor ( IGF IR ) gene expression and to determine the small intestinal morphology . ^^^ In both experiments , the villous height of the small intestinal mucosa and both the mRNA and protein levels for IGF 1 and IGF IR in the small intestine were markedly enhanced ( P < 0 . 05 ) by feeding elevated levels of Zn . ^^^ Collectively , these results suggest that dietary Zn supplementation exerts its beneficial effects on the intestinal growth of weanling piglets through increasing IGF 1 and IGF IR expression in the small intestinal mucosa . . ^^^ Dietary supplementation with zinc oxide increases Igf 1 and Igf 1 receptor gene expression in the small intestine of weanling piglets . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
In contrast , a significant inhibition of growth and increase of apoptosis of K562 / AC cells were induced by IGF 1 receptor neutralizing antibody , or suramin , a nonspecific growth factor antagonist . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The nuclear transcription factor cAMP response element binding protein ( CREB ) may also be involved although relationships between these two proteins in IGF 1 receptor signaling and protection is not clear , especially in neuronal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Here , we show that the receptor interacting protein ( RIP ) , a key mediator of tumor necrosis factor induced NF kappaB and JNK activation , plays a key role in IGF 1 receptor signaling . ^^^ More importantly , RIP was recruited to the IGF 1 receptor complex during IGF 1 induced signaling . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We therefore aimed to evaluate IGF IR and IGF 1 mRNA expression in liver from patient with CHC . ^^^ METHODS : IGF IR and IGF 1 mRNA content were determined by semi quantitative RT PCR and IGF IR protein expression was determined by immunohisto chemistry in hepatic tissue obtained from patients with CHC before ( 34 patients ) and after ( 10 patients ) therapy with interferon alpha and ribavirin . ^^^ RESULTS : An increase of IGF IR mRNA content was observed in hepatic tissue obtained from all CHC patients as well as from 6 cadaveric liver donors following orthopic transplantation ( an attempt to evaluate normal livers ) in comparison to normal liver , while no relevant modifications were detected in IGF 1 mRNA content . ^^^ Considering that liver is the organ with the highest levels of IGF 1 , our finding of increased IGF IR expression after both acute and chronic hepatic damage highlights the need for additional studies to elucidate the role of IGF 1 in liver regeneration . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor ( IGF1R ) is a transmembrane tyrosine kinase , which is indispensable for cellular growth and differentiation . ^^^ Hydrogen peroxide inhibits activity of the IGF 1 receptor kinase . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The insulin like growth factor 1 receptor ( IGF IR ) mediates the biological actions of both IGF 1 and IGF 2 . ^^^ The mode of action of many tumor suppressors involves transcriptional suppression of the IGF IR gene , with a subsequent reduction in cell surface IGF IR concentrations and IGF 1 action . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
This review is a critical appraisal of the role of IGFs , IGFBP , and IGF 1 receptor ( the IGF axis ) in both experimental and clinical prostate cancer genesis and progression . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The current data show that neuroblastoma cells with high IGF IR expression , either endogenously or through transfection , adhere to human bone marrow endothelial cells and subsequently migrate toward both IGF 1 and human bone stromal cells . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
They were assessed in right vastus lateralis muscle for insulinlike growth factor 1 ( IGF IEa and IGF IEc ) , IGF 2 , the IGF 1 receptor , the IGF 2 receptor , and myostatin . mRNA was measured by real time polymerase chain reaction amplification of reverse transcribed cDNA . ^^^ The results showed that in the MHD patients , as compared with the normal control patients , skeletal muscle mRNA levels for IGF IEa , IGF 2 , and the IGF 1 receptor were significantly reduced , whereas mRNA for IGF IEc , IGF 2 receptor , and myostatin were not different than normal . ^^^ We conclude that sedentary MHD patients show reductions in mRNA levels in the right vastus lateralis muscle for certain growth factor proteins , notably IGF IEa , IGF 2 , and the IGF 1 receptor . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 receptor is essential for the establishment of hippocampal neuronal polarity . ^^^ Results obtained with a function blocking antibody and an siRNA targeting the insulin like growth factor 1 ( IGF 1 ) receptor suggest that an essential step in the establishment of hippocampal neuronal polarity and the initiation of axonal outgrowth is the activation of the phosphatidylinositol 3 kinase ( PI3k ) Cdc 42 pathway by the IGF 1 receptor , but not by the TrkA or TrkB receptors . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Consistent with results obtained using HER 2 or IGF IR transfected cells ( MCF 7 / HER2 18 and SKBR3 / IGF IR , respectively ) , we found that rhIGFBP 3 significantly reduced IGF 1 induced IGF IR phosphorylation and displayed a synergistic interaction with Herceptin against cultured HER 2 overexpressing breast cancer cells in vitro . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Pancreatic carcinoma cells overexpress the insulin like growth factor 1 ( IGF 1 ) receptor ( IGF IR ) and the hepatocyte growth factor ( HGF ) receptor , c Met , which are both known to mediate tumor cell migration and invasion . ^^^ We hypothesized that IGF IR and c Met cooperate to induce migration and invasion of human pancreatic carcinoma cells and that IGF 1 mediated migration and invasion depend on c Met . ^^^ To determine if c Met is necessary for IGF IR mediated migration and invasion , c Met was down regulated in L3 . 6pl cells via adenoviral infection with a c Met ribozyme before IGF 1 treatment . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IL 1beta enhanced expression of IGF IR levels , as determined by both [ 125I ] IGF 1 binding studies and Western blotting , while reducing the concentration of endogenous IGF 1 detected in conditioned media by radioimmunoassay . ^^^ Northern blot analysis suggested IL 1beta regulation of IGF 1 and , to some extent , IGF IR was mediated by transcription ; however , the cytokine did not affect IGFBP 2 expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Ethanol also reduced insulin , IGF 1 , and IGF 2 receptor binding , insulin and IGF 1 receptor tyrosine kinase activities , ATP , membrane cholesterol , and choline acetyltransferase ( ChAT ) expression . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
To investigate their roles in tooth movement , root resorption , and repair , the occurrence of components of the IGF system , including the ligands IGF 1 and 2 , the IGF receptor 1 ( IGF1R ) and six IGF binding proteins ( IGFBP 1 to 6 ) , was investigated by immunohistochemistry on sections from rat maxillae where the first molar had been moved mesially by means of an orthodontic appliance for 9 d to induce root resorption . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
Insulin and the new long acting insulin analog , glargine , interacted with the IGF IR with over thousand and 100 fold less potency than IGF 1 itself , whereas IGF 2 had 6 times lower potency than IGF 1 . ^^^ Phosphorylation of the IGF IR beta subunit was obtained by concentrations of 10 ( 10 ) 10 ( 8 ) M IGF 1 , 10 ( 6 ) M of insulin , inconsistently by 10 ( 8 ) M insulin and not at all by 10 ( 10 ) 10 ( 9 ) M insulin . ^^^ Both IGF 1 and insulin phosphorylate their receptors , but only IGF 1 seems to phosphorylate Hybrid IR / IGF IR . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We investigated the expression of estrogen receptors ( ERs ) , insulin like growth factor 1 ( IGF 1 ) , and IGF 1R ( receptor ) in human cholangiocarcinoma and cholangiocarcinoma cell lines ( HuH 28 , TFK 1 , Mz ChA 1 ) , evaluating the role of estrogens and IGF 1 in the modulation of neoplastic cell growth . ^^^ ER alpha , ER beta , IGF 1 , and IGF 1R were expressed ( immunohistochemistry ) in all biopsies ( 18 of 18 ) of intrahepatic cholangiocarcinoma . ^^^ ER alpha was expressed ( Western blot ) only by the HuH 28 cell line ( intrahepatic cholangiocarcinoma ) , whereas ER beta , IGF 1 , and IGF 1R were expressed in the three cell lines examined . ^^^ In serum deprived HuH 28 cells , serum readmission induced stimulation of cell proliferation that was inhibited by ER and IGF 1R antagonists . 17beta Estradiol and IGF 1 stimulated proliferation of HuH 28 cells to a similar extent to that of MCF 7 ( breast cancer ) but greater than that of TFK 1 and Mz ChA 1 , inhibiting apoptosis and exerting additive effects . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
We also used IGF 1 receptor antibody to inhibit the action of IGF 1 and studied its effect on alpha sma and type 1 collagen . ^^^ IGF 1 induced increase in alpha sma expression and type 1 collagen was significantly inhibited by pretreatment with LY 294002 and IGF 1 receptor antibody . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
As insulin like growth factor ( IGF ) signaling has been recognized to play an important role in human cancer , the IGF 1 receptor ( IGF IR ) is currently the focus of intensive research aimed at developing novel antitumor agents . ^^^ The IGF system is frequently deregulated in cancer cells by the establishment of autocrine loops involving IGF 1 or 2 and / or IGF IR over expression . ^^^
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CD45neg but not CD45pos human myeloma cells are sensitive to the inhibition of IGF 1 signaling by a murine anti IGF 1R monoclonal antibody , mAVE 1642 . ^^^
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OBJECTIVE : To determine whether the insulin receptor ( IR ) , insulin like growth factor 1 receptor ( IGF IR ) , and IGF 1 are expressed differentially in fibroblasts isolated from normal peritoneal and adhesion tissue before and after 24 hour treatment with increasing glucose concentrations . ^^^ MAIN OUTCOME MEASURE ( S ) : Real time polymerase chain reaction was used to measure messenger RNA ( mRNA ) levels for IR , IGF IR , and IGF 1 . ^^^ RESULT ( S ) : At the normal glycemic level ( 100 mg / dL ) , adhesion fibroblasts have significantly higher mRNA levels of the IR ( 7 . 96 + / 0 . 15 vs . 6 . 97 + / 0 . 16 ; P < . 05 ) , IGF IR ( 7 . 72 + / 0 . 22 vs . 6 . 88 + / 0 . 06 ; P < . 05 ) , and IGF 1 ( 7 . 04 + / 0 . 10 vs . 5 . 92 + / 0 . 10 ; P < . 05 ) when compared with normal fibroblasts , respectively . ^^^ Normal fibroblasts respond to increasing glucose concentrations by increasing the expression levels of the IR , IGF IR , and IGF 1 , whereas adhesion fibroblasts respond by decreasing the expression of the IR , IGF IR , and IGF 1 . ^^^ CONCLUSION ( S ) : The differential expression of the IR , IGF IR , and IGF 1 in adhesion fibroblasts may contribute to the pathogenesis of fibrosis observed in diabetic patients . . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
IGF 1 enhanced the phosphorylation of IGF 1R , Akt and Erk1 / 2 in KYN 2 cells , and coadministration of IGFBP 3 blocked all types of activation by IGF 1 investigated here . ^^^
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
The expressions of IGF 1 and IGF 1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function . ^^^ Positive immunostaining for IGF 1 and IGF 1 receptor proteins was enhanced in myocardial biopsies from failing hearts compared with those from nonfailing hearts . ^^^
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Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
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Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA
Interacting proteins: P05019 and P08069 Pubmed SVM Score :0.0
NA