Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.60564976
Association of IRS 1 with the insulin receptor and the phosphatidylinositol 3 ' kinase . 0.60564976^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.55095268
Evidence for a direct interaction between insulin receptor substrate 1 and Shc . 0.55095268^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.58315974
Insulin signaling is initiated at least in part by activation of the insulin receptor tyrosine kinase and subsequent phosphorylation of cellular substrates such as insulin receptor substrate 1 ( IRS 1 ) . 0.58315974^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.95761682
Using the yeast two hybrid system , a genetic assay for studying protein protein interactions , we have examined and compared the interaction of the insulin like growth factor 1 receptor ( IGF IR ) and the insulin receptor ( IR ) with their two known substrates p52Shc and the insulin receptor substrate 1 ( IRS 1 ) . 0.95761682^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.63501469
TNF effect on IRS 1 in Fao hepatoma cells was not associated with a significant reduction in insulin receptor tyrosine kinase activity as measured in vitro but impaired the association of IRS 1 with phosphatidylinositol 3 kinase , localizing TNF impact to IRS 1 . 0.63501469^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :1.1570848
To characterize the structural basis for the interactions between the insulin receptor ( IR ) and its major substrate , insulin receptor substrate 1 ( IRS 1 ) , a segment of the NH 2 terminal region of IRS 1 ( Pro 5 Pro65 ) was deleted . 1.1570848^^^ This could account for the fact that partial deletion of the PH domain selectively impairs the in vivo interactions between the insulin receptor and IRS 1 , whereas their in vitro interactions remain unaffected . . 0.8938075^^^ These findings suggest that the overall structure of IRS 1 is not altered by deletion of its PH domain and that the PH domain is not the main site for protein protein interactions between the insulin receptor and IRS 1 , at least in vitro . 0.50082357^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.7661891
To study the interaction of the insulin receptor with IRS 1 in vitro , we expressed in Escherichia coli the amino acids 516 777 of human IRS 1 ( hIRS p 30 ) covering five potential tyrosine phosphorylation sites within YXXM motifs . 0.7661891^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.72770074
Characterization of an interaction between insulin receptor substrate 1 and the insulin receptor by using the two hybrid system . 0.72770074^^^ Although IRS 1 is thought to interact with the insulin receptor , the nature of the interaction has not been defined . 0.6391418^^^ We demonstrate that IRS 1 forms a specific complex with the cytoplasmic domain of the insulin receptor when both are expressed as hybrid proteins in yeast cells . 0.61033779^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.50045723
Here , insulin dependent insulin receptor tyrosine kinase activation was examined with recombinant insulin receptor substrate 1 ( IRS 1 ) as the substrate and shown to be 3 fold greater in cells with suppressed LAR levels . 0.50045723^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :1.0863892
These interactions explain why IRS 1 binds to the insulin receptor but not to NPXpY motifs in growth factor receptors . 1.0863892^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.64913556
Expression of a carboxy terminal truncated IRS 1 molecule containing the pleckstrin homology and phosphotyrosine binding domains associates with the insulin receptor and prevents tyrosyl phosphorylation of endogenous IRS 1 and Shc proteins . 0.64913556^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.89330109
In the present study , we have examined the levels and phosphorylation state of the insulin receptor and of insulin receptor substrate 1 ( IRS 1 ) , as well as the association between IRS 1 and phosphatidylinositol 3 kinase ( PI 3 kinase ) in the liver and muscle of pregnant rats ( day 20 of gestation ) by immunoprecipitation and immunoblotting with anti insulin receptor , anti IRS 1 , anti PI 3 kinase and anti phosphotyrosine antibodies . 0.89330109^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :1.1078723
Because of competition between Shc and IRS 1 for interaction with the insulin receptor , insulin stimulated tyrosine phosphorylation of IRS 1 was decreased in WT Shc cells compared with that in HIRc cells . 1.1078723^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.76127495
We conclude that stable association of IRS 1 with the insulin receptor is unaffected by disruption of PTB domain Tyr 960 interactions but requires the IRS 1 PH domain , and that efficient phosphorylation of IRS 1 in intact cells correlates with the formation of stable receptor IRS complexes . . 0.76127495^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.60861279
Among these three , the motif around Ser 270 is located in the phosphotyrosine binding domain of IRS 1 , which is responsible for the interaction with the insulin receptor . 0.60861279^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.86024946
A 973 valine to methionine mutation of the human insulin receptor : interaction with insulin receptor substrate 1 and Shc in HEK 293 cells . 0.86024946^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.77884507
Activated insulin receptor ( IR ) interacts with its substrates , IRS 1 , IRS 2 , and Shc via the NPXY motif centered at Y 960 . 0.77884507^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.75703092
In the present study , we examined the phosphorylation status of the insulin receptor and IRS 1 , as well as the association between IRS 1 and PI 3 kinase in the liver and muscle of 20 month old rats treated acutely with captopril , using immunoprecipitation with antipeptide antibodies to the insulin receptor and IRS 1 , and immunoblotting with antiphosphotyrosine and anti PI 3 kinase antibodies . 0.75703092^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.70355884
Treating cells with C 2 ceramide does not affect phosphorylation of insulin receptor substrate 1 , interactions between insulin receptor substrate 1 and p 85 , or insulin stimulated phosphatidylinositol 3 kinase activity , suggesting that the effects of C 2 ceramide on Akt kinase are not mediated through modulating phosphatidylinositol 3 kinase . 0.70355884^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.57428333
The results demonstrated that ethanol treatment ( 100 mM ) caused 30 to 50 % reductions in the levels of insulin stimulated tyrosyl phosphorylation of the insulin receptor beta subunit , tyrosyl phosphorylation of IRS 1 , phosphorylation of Erk 2 , association of phosphatidylinositol 3 kinase with tyrosyl phosphorylated IRS 1 , and MAP kinase and phosphatidylinositol 3 kinase activities . 0.57428333^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.6766935
We postulate that during regulated insulin secretion , released insulin binds the beta cell insulin receptor and activates IRS 1 , thus further increasing cytosolic Ca2+ by reducing Ca2+ uptake . 0.6766935^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.89932232
In the present study we have examined the levels and phosphorylation state of the insulin receptor and of insulin receptor substrate 1 ( IRS 1 ) , as well as the association between IRS 1 and phosphatidylinositol 3 kinase ( PI 3 kinase ) in the liver and muscle of septic rats by immunoprecipitation and immunoblotting with anti insulin receptor , anti IRS 1 , anti PI 3 kinase and anti phosphotyrosine antibodies . 0.89932232^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.67507862
Although plasma insulin had reached 98 % of its final concentration within 10 min , insulin receptor kinase ( IRK ) activity , p 85 associated with insulin receptor substrate 1 ( IRS 1 ) , IRS 1 associated phosphatidylinositol 3 kinase ( PI3K ) activity , and Thr ( 308 ) protein kinase B ( PKB ) phosphorylation in the muscle biopsies at 20 min had reached only 60 , 48 , 34 and 47 % respectively of those at 180 min . 0.67507862^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.5740822
The development of insulin resistance was determined by tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 , phosphatidylinositol 3 kinase activity associated with insulin receptor substrate 1 and glucose uptake . 0.5740822^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.90888692
This controls many aspects of IRS 1 , including its interaction with the insulin receptor and subsequent tyrosine phosphorylation , as well as its subcellular distribution and targeting for degradation by the proteasome . 0.90888692^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.75167284
The insulin receptor is a ligand activated tyrosine kinase that phosphorylates its major substrate protein , insulin receptor substrate 1 ( IRS 1 ) , at multiple sites . 0.75167284^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :1.0407274
LIP in CON reduced insulin stimulated glucose disposal ( Rd ) by 25 % , insulin stimulated insulin receptor tyrosine phosphorylation by 17 % , phosphatidylinositol 3 kinase activity associated with insulin receptor substrate 1 by 20 % , and insulin stimulated glycogen synthase fractional velocity over baseline ( 44 vs . 15 % ; all P < 0 . 05 ) . 1.0407274^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.5711824
This was due to the ability of IRS 1 ( 7A ) to remain complexed with the insulin receptor ( IR ) , unlike IRS 1 ( WT ) , which underwent Ser phosphorylation , resulting in its dissociation from IR . 0.5711824^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also show that a 173 residue region of insulin receptor substrate 1 ( IRS 1 ; residues 144 316 ) has related PTB activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth hormone stimulates tyrosine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 gene and cardiovascular risk factors in NIDDM . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It also was not bound to the insulin receptor , phosphatidylinositol 3 kinase or insulin receptor substrate 1 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , forskolin did not inhibit insulin stimulated tyrosine phosphorylation of the insulin receptor substrate IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate ( IRS 1 ) gene polymorphisms in French NIDDM families . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is phosphorylated by the serine kinase activity of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The overexpression of insulin receptor makes CHO cells resistant to the action of IGF 1 : role of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The human insulin receptor substrate 1 gene ( IRS 1 ) is localized on 2q36 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A complex of GRB 2 dynamin binds to tyrosine phosphorylated insulin receptor substrate 1 after insulin treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The results of the present study show that another target of this kinase is the insulin receptor substrate , IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
There was near complete absence of insulin receptor substrate 1 ( IRS 1 ) in the cell ghosts after permeabilization . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cloning of the mouse insulin receptor substrate 1 ( IRS 1 ) gene and complete sequence of mouse IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 is a principal substrate of the insulin receptor tyrosine kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate protein 1 ( IRS 1 ) could not be detected in the nucleus by immunoblotting . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both IRS 1 and Shc are phosphorylated by the insulin receptor tyrosine kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IFN alpha also induces tyrosine phosphorylation of IRS 1 , the principle substrate of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin dependent tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and Shc was 3 fold greater in CD 45 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Similar results have been found concerning the tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
By comparison with the insulin receptor , p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Human insulin receptor substrate 1 : variant sequences in familial non insulin dependent diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Deletion of Gly 723 in the insulin receptor substrate 1 of a patient with noninsulin dependent diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No change in 5 ' phosphatase activity was detected in insulin receptor or IRS 1 immune complexes in response to insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Among the multiple substrates , the insulin receptor substrate 1 ( IRS 1 ) is the major cytoplasmic substrate for insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
All of the fusion receptors can phosphorylate insulin receptor substrate 1 and activate PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Whereas IRS 1 is located on murine chromosome 1 , IRS 2 is located on murine chromosome 8 near the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
The large docking protein IRS 1 is a major substrate for the insulin receptor and other tyrosine kinases . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin dramatically increased insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation ( p < 0 . 05 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance and hyperinsulinaemia in insulin receptor substrate 1 knockout mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance syndrome in mice deficient in insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) gene ] . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
APP stimulated the tyrosine phosphorylation of a number of proteins including insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is expressed at high levels in all cells of the peri implantation mouse embryo . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Isolation and characterization of the chicken insulin receptor substrate 1 gene . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The family of insulin receptor substrates ( IRS 1 4 ) is defined by proteins with an overall similar structure . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The level of insulin receptor substrate 1 ( IRS 1 ) protein was decreased by 60 % in control SHROB compared with lean SHR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In cultured cells , GH stimulates the tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , IRS 2 , and Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced insulin receptor substrate 1 degradation is mediated by the proteasome degradation pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent studies have identified several polymorphisms in the human insulin receptor substrate 1 ( IRS 1 ) gene . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin like growth factor 1 activates insulin receptor substrate 1 and Ras in human osteosarcoma cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor substrate 1 ( IRS 1 ) by protein kinase B positively regulates IRS 1 function . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , birth weights were reduced in insulin receptor substrate 1 knockout mice despite normal insulin levels . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PMA also decreased IGF 1 induced tyrosine phosphorylation of insulin receptor substrate 1 and its association with PI3K . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Kinase activity towards insulin receptor substrate 1 and insulin binding were then measured in these wells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PI3K activation was inhibited by wortmannin and was not dependent upon insulin receptor substrate 1 activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Gly972Arg variant in insulin receptor substrate 1 is not associated with birth weight in contemporary English children . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The common Arg 972 polymorphism in insulin receptor substrate 1 causes apoptosis of human pancreatic islets . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Novel silent variant ( c1722G > A ) in the coding region of the insulin receptor substrate 1 ( IRS 1 ) gene . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor substrate 1 and 2 in ovaries from women with insulin resistance and from controls . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Additionally , CEACAM 1 binding to Shc enhances its ability to compete with IRS 1 for phosphorylation by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Apomorphine , dopamine and phenylethylamine reduce the proportion of phosphorylated insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Neither treatment had any effect on basal insulin receptor substrate 1 ( IRS 1 ) associated PI 3 kinase activity in muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol ( PI ) 3 kinase activity is unaffected ( 30 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin resistant rodents . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The type 2 vascular endothelial growth factor receptor recruits insulin receptor substrate 1 in its signalling pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Polymorphisms in insulin receptor substrate 1 ( IRS 1 ) gene ] . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate 1 ( IRS 1 ) can translocate to the nuclei and nucleoli of several types of cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
HG culturing also enhanced leptin stimulated insulin receptor substrate 1 ( IRS 1 ) and MAPK phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
High insulin had no effect on glucose transport or the expression of insulin receptor 1 ( IRS 1 ) . 3 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SIK 2 is found in adipocytes and phosphorylates a specific serine residue in insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of insulin receptor substrate 1 with insulin stimulation was not significantly affected . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance due to phosphorylation of insulin receptor substrate 1 at serine 302 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Several polymorphisms in the insulin receptor substrate 1 ( IRS 1 ) gene have been reported in the last years . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
GLUT 4 translocation was increased through insulin receptor substrate 1 ( IRS 1 ) PI 3 kinase Akt signaling mechanism . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Influence of alcohol on insulin sensitivity and insulin receptor substrate 1 mRNA expression in rat skeletal muscle ] . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both Cr and Zn could phosphorylate insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) mediates signaling from the insulin like growth factor type 1 receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The protein content of insulin receptor beta subunit , IRS 1 and 2 , did not differ between groups . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is required for bone anabolic function of parathyroid hormone in mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Inducible nitric oxide synthase and NO donor induce insulin receptor substrate 1 degradation in skeletal muscle cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in growth hormone treated animals . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
T antigen does not operate directly but utilizes a cytosolic molecule , insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
One mechanism is insulin activated signaling through insulin receptor substrate 1 and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No increase in insulin receptor substrate 1 ( IRS 1 ) or total PKB / Akt ( Akt ) was detected in the resistant cell lines . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No association between genetic polymorphisms in insulin and insulin receptor substrate 1 and prostate cancer . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Variation of the insulin receptor substrate gene ( IRS 1 ) in African Pygmies and Bantus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Direct cross talk of interleukin 6 and insulin signal transduction via insulin receptor substrate 1 in skeletal muscle cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Feedback control in insulin signaling involves serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regulation of insulin receptor substrate 1 pleckstrin homology domain by protein kinase C : role of serine 24 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Leptin down regulates insulin action through phosphorylation of serine 318 in insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This IGF 1 resistance was associated with enhanced Ser ( 307 ) phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These genes were FOXO1A , INSR , IRS 1 , PIK3CB , PIK3CG , and PPARGC1A . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Additionally , SOCS 7 associated with the INSR and IRS 1 molecules that are essential for normal regulation of insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cloning and increased expression of an insulin receptor substrate 1 like gene in human hepatocellular carcinoma . ^^^ Human insulin receptor substrate 1 ( hIRS 1 ) cDNAs were cloned from a lambda GT 11 expression library using a monoclonal antibody ( MAb ) produced against a human hepatocellular carcinoma ( HCC ) cell line ( FOCUS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Of 34 tyrosine residues in insulin receptor substrate 1 ( IRS 1 ) , 14 are adjacent to acidic residues , suggesting that they might be phosphorylation sites . ^^^ YMXM motifs of IRS 1 define substrate specificity of the insulin receptor kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Non tyrosine kinase pathways that could signal insulin effects through the insulin receptor include non covalent activation of G proteins , phospholipase Cs , or docking proteins such as IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regulation of insulin receptor substrate 1 in liver and muscle of animal models of insulin resistance . ^^^ This protein , termed insulin receptor substrate 1 ( IRS 1 ) , has been implicated in insulin signal transmission based on studies with insulin receptor mutants . ^^^ In the present study we have examined the levels of IRS 1 and the phosphorylation state of insulin receptor and IRS 1 in liver and muscle after insulin stimulation in vivo in two rat models of insulin resistance , i . e . , insulinopenic diabetes and fasting , and a mouse model of non insulin dependent diabetes mellitus ( ob / ob ) by immunoblotting with anti peptide antibodies to IRS 1 and anti phosphotyrosine antibodies . ^^^ These data indicate that : ( a ) IRS 1 protein levels are differentially regulated in liver and muscle ; ( b ) insulin levels may play a role in this differential regulation of IRS 1 ; ( c ) IRS 1 phosphorylation depends more on insulin receptor kinase activity than IRS 1 protein levels ; and ( d ) reduced IRS 1 phosphorylation in liver and muscle may play a role in insulin resistant states , especially of the ob / ob mice . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 is an insulin receptor substrate that undergoes tyrosine phosphorylation and associates with the phosphatidylinositol ( PtdIns ) 3 ' kinase immediately after insulin stimulation . ^^^ Recombinant IRS 1 protein was tyrosine phosphorylated by the insulin receptor in vitro and associated with the PtdIns 3 ' kinase from lysates of quiescent 3T3 fibroblasts . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin dependent formation of a complex containing an 85 kDa subunit of phosphatidylinositol 3 kinase and tyrosine phosphorylated insulin receptor substrate 1 . ^^^ Insulin also induced an association of p 85 with the tyrosine phosphorylated insulin receptor substrate 1 ( IRS 1 ) and other phosphorylated proteins ranging in size from 100 to 170 kDa but not with the activated insulin receptor . ^^^ In vitro reconstitution studies were used to show p 85 in the active PI 3 kinase associated with the tyrosine phosphorylated IRS 1 but not with the activated insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Intracellular signalling is dependent on ligand activated tyrosine kinase activity in the transmembrane beta subunit , which phosphorylates both the receptor itself and the specific substrate insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , a synthetic phosphopeptide ( 13 mer ) containing sequences conserved between the major tyrosine phosphorylation site of murine polyoma virus mT , hamster polyoma virus mT , and the insulin receptor substrate ( IRS 1 ) specifically blocked the association of the 85 and 110 kDa polypeptides with the mT pp60c src complex . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The major cytosolic substrate of the insulin receptor is a 185 kDa phosphoprotein ( IRS 1 ) that contains multiple putative attachment sites for the p 85 alpha regulatory subunit of phosphatidylinositol 3 ' kinase ( PI3K ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 and pp 185 undergo tyrosine phosphorylation immediately after insulin stimulation and show an insulin dose response similar to that of insulin receptor autophosphorylation . ^^^ Our results show that Fao cells contain at least two insulin receptor substrates , IRS 1 and HMW pp 185 , which may play unique roles in insulin signal transmission . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The polypeptides of 175 , 41 , and 37 kDa were tentatively identified as the insulin receptor substrate 1 ( IRS 1 ) and extracellular signal regulated kinases 1 and 2 ( ERK 1 and 2 ) , respectively , by immunoblotting with antibodies specific for these proteins , and the 115 and 100 kDa polypeptides are probably the beta subunits of the insulin and IGF 1 receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulation of phosphatidylinositol 3 kinase activity and association with insulin receptor substrate 1 in liver and muscle of the intact rat . ^^^ Insulin rapidly stimulates tyrosine phosphorylation of its endogenous substrate , insulin receptor substrate 1 ( IRS 1 ) , and in vitro IRS 1 associates with PI 3 kinase , thus activating the enzyme . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 is a major insulin receptor substrate which may play an important role in insulin signal transmission . ^^^ Expression of the human insulin receptor and rat IRS 1 together in CHO / IR / IRS 1 cells increased the basal serine phosphorylation of IRS 1 and strongly increased tyrosine phosphorylation during insulin stimulation . ^^^ Some IRS 1 associated with the insulin receptor during insulin stimulation . ^^^ In addition , a phosphatidylinositol 3 ' kinase associated with IRS 1 during insulin stimulation , and this association was more sensitive to insulin in CHO cells overexpressing the insulin receptor ( CHO / IR cells ) , more responsive to insulin to CHO / IRS 1 cells , and both sensitive and responsive in CHO / IR / IRS 1 cells . ^^^ Together , these results suggest that IRS 1 is a direct physiologic substrate of the insulin receptor and may play an important role in insulin signal transmission . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd ( insulin receptor substrate 1 or IRS 1 ) in most cell types . ^^^ Tyrosine phosphorylation of insulin receptor and of IRS 1 have been implicated in insulin signal transmission based on studies with insulin receptor mutants . ^^^ In the study presented here , the levels and phosphorylation state of the insulin receptor and IRS 1 in liver and muscle after insulin stimulation in vivo have been examined in spontaneously hypertensive rats ( SHR ) by immunoblotting with antipeptide antibodies to insulin receptor and IRS 1 and antiphosphotyrosine antibodies . ^^^ It was found that the levels of insulin receptor and IRS 1 protein in liver and muscle are similar in controls ( Wistar Kyoto rats ) and SHR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Structure of the insulin receptor substrate IRS 1 defines a unique signal transduction protein . ^^^ Thus IRS 1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Among these steps are phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and activation of phosphatidylinositol 3 kinase ( P 13 kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Autophosphorylation sites in the PDGFr directly bind SH 2 proteins , whereas activation of the insulin receptor leads to phosphorylation of IRS 1 , which in turn binds SH 2 proteins . ^^^ These results support the hypothesis that IRS 1 differentiates the signals generated by the insulin receptor and PDGFr tyrosine kinases by binding and regulating a specific subset of SH 2 domain containing signaling molecules . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cloning of a cDNA encoding a 190 kDa insulin receptor substrate 1 like protein of simian COS cells . ^^^ Major insulin signals such as stimulation of glucose uptake and DNA synthesis and modification of hexose metabolism are mediated by the tyrosine phosphorylated insulin receptor substrate 1 ( IRS 1 ; pp 180 ) in many species of cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate 1 related 4PS substrate but not the interleukin 2R gamma chain is involved in interleukin 13 mediated signal transduction . ^^^ IL 13 and IL 4 stimulation of murine L cell fibroblasts , which endogenously express the IL 4 receptor ( IL 4R alpha ) and lack expression of the IL 2 receptor gamma subunit ( IL 2R gamma ) , resulted in tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) / 4PS . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Adapter function of protein tyrosine phosphatase 1D in insulin receptor / insulin receptor substrate 1 interaction . ^^^ Insulin signal transduction involves the multisite docking protein insulin receptor substrate 1 ( IRS 1 ) and a number of Src homology 2 ( SH 2 ) domain factors , including p85 / p110 phosphatidylinositol 3 kinase , p 110 GTPase activating protein , and the phosphotyrosine specific phosphatase PTP1D . ^^^ While the receptor and the phosphatase do not serve as substrates for each other , their interaction promotes IRS 1 binding to the receptor , indicating that PTP1D functions as an adapter for insulin receptor and IRS 1 . ^^^ The formation of a multiprotein signaling complex involving the insulin receptor , PTP1D , and IRS 1 enhances cellular glucose uptake , a critical process in the physiological action of insulin . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , they fail to undergo insulin stimulated internalization , do not regulate the phosphorylation of insulin receptor substrate 1 , and are unable to mediate an insulin stimulated increase in DNA synthesis and c jun and c fos expression . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Thrombin stimulates phosphorylation of insulin like growth factor 1 receptor , insulin receptor substrate 1 , and phospholipase C gamma 1 in rat aortic smooth muscle cells . ^^^ These proteins are insulin like growth factor 1 receptor beta subunit ( IGF IR beta ) , insulin receptor substrate 1 ( IRS 1 ) , and phospholipase C gamma 1 ( PLC gamma 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We conclude that Tyr phosphorylated insulin receptor substrate 1 is the main upstream regulator of insulin induced S 6 phosphorylation by p70s6k , whereas MAPK signaling seems to be activated in these cells primarily through the adaptor molecule Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 ( insulin receptor substrate 1 ) is a principal insulin receptor substrate that undergoes tyrosine phosphorylation during insulin stimulation . ^^^ IRS 1 ( insulin receptor substrate 1 ) is a principal insulin receptor substrate that undergoes tyrosine phosphorylation during insulin stimulation . ^^^ We identified some of the tyrosine residues of IRS 1 that undergo insulin stimulated phosphorylation by the purified insulin receptor and in intact cells during insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This protein , insulin receptor substrate 1 ( IRS 1 ) , has been implicated as the first postreceptor step in insulin signal transmission based on studies with insulin receptor mutants . ^^^ Thus , the insulin receptor , IRS 1 and PI 3 kinase represent three of the earliest steps in insulin action at the cellular level . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunocytochemical detection of insulin receptor substrate 1 ( IRS 1 ) in rat brain : colocalization with phosphotyrosine . ^^^ In peripheral insulin sensitive tissues , insulin receptor substrate ( IRS 1 ) undergoes tyrosine phosphorylation immediately after cells are stimulated by insulin or insulin like growth factor 1 ( IGF 1 ) , and may function as a molecular link between insulin / IGF 1 receptor tyrosine kinases and enzymes regulating cell growth and metabolism . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Correlation of the insulin receptor substrate 1 with insulin responsive deoxyglucose transport in 3T3 L 1 adipocytes . ^^^ We have devised procedures for decreasing the amount of IRS 1 in 3T3 L 1 adipocytes ( viz . , chronic treatments with insulin , dexamethasone , 1 methyl 3 isobutylxanthine , cycloheximide or actinomycin D ) and have determined the correlation between the amounts of IRS 1 , insulin receptor , GluT 4 and phosphatidylinositol 3 ' kinase regulatory subunit with insulin responsive dGlc transport . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have examined the involvement of insulin receptor ( IR ) substrate 1 ( IRS 1 ) and / or Shc in the upstream of Ras activation in insulin signaling using Chinese hamster ovary ( CHO ) cell lines overexpressing wild type ( CHO IR ) cells ) or mutant insulin receptors . ^^^ In contrast , a CHO cell line overexpressing the kinase negative mutant insulin receptor substituting Arg 1018 for Lys 1018 was unable to tyrosine phosphorylate IRS 1 and Shc and failed to activate Ras in response to insulin . ^^^ A CHO cell line overexpressing the mutant insulin receptor , substituting Ala 960 for Tyr 960 and which was known to exhibit impaired tyrosine phosphorylation of IRS 1 and biological effects evoked by insulin , showed severely impaired insulin dependent tyrosine phosphorylation of Shc and moderately impaired activation of Ras . ^^^ Another cell line overexpressing the mutant insulin receptor , lacking 82 amino acids of the C terminus of beta subunit and which was recently reported to retain normal insulin dependent tyrosine phosphorylation of IRS 1 , showed slightly impaired Ras activation at 10 ( 7 ) M insulin with severely reduced tyrosine phosphorylation of Shc protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families , including glucokinase regulatory protein , hexokinase 2 , insulin receptor substrate 1 , fatty acid binding protein 2 , glucagon like peptide 1 receptor , apolipoprotein C 2 , glycogen synthase , adenosine deaminase ( a marker for the MODY gene on chromosome 20 ) , and phosphoenolpyruvate carboxykinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ethanol impairs insulin receptor substrate 1 mediated signal transduction during rat liver regeneration . ^^^ Insulin is a potent hepatotrophic factor and it was determined if ethanol interferes with insulin receptor substrate ( IRS 1 ) protein mediated signal transduction during liver regeneration . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Src homology 2 domains of protein tyrosine phosphatase are associated in vitro with both the insulin receptor and insulin receptor substrate 1 via different phosphotyrosine motifs . ^^^ To clarify the role of protein tyrosine phosphatase containing Src homology 2 ( SH 2 ) regions on insulin signaling , we investigated the interactions among the insulin receptor , a pair of SH 2 domains of SH PTP 2 coupled to glutathione S transferase ( GST ) and insulin receptor substrate 1 ( IRS 1 ) GST fusion protein ( amino portion , IRS IN ; carboxyl portion , IRS 1C ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The two receptors bound IGF 1 with similar affinity ( Kd approximately 1 . 7 nM ) , but the CAG form exhibited an approximately 2 fold increase in IGF 1 stimulation of receptor autophosphorylation , insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , thymidine incorporation , and IRS 1 associated phosphatidylinositol 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) expression in rat brain . ^^^ IRS 1 mRNA was colocalized with insulin receptor mRNA in neuron cell bodies of hippocampus and olfactory bulb . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activation of protein kinase C alpha inhibits insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 . ^^^ Activation of PKC by 12 O tetradecanoylphorbol 13 acetate in the CHO PKC alpha cells inhibited by approximately 75 % the : 1 ) insulin stimulated increase in antiphosphotyrosine precipitable phosphatidylinositol 3 kinase activity in these cells ; 2 ) insulin stimulated increase in PI 3 kinase activity associated with insulin receptor substrate 1 ; and 3 ) tyrosine phosphorylation of the endogenous substrate , insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Gln 1131 mutation impaired the activity of the receptor tyrosine kinase and inhibited the ability of insulin to phosphorylate the endogenous substrate insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activation of PI 3 kinase in 3T3 L 1 adipocytes by association with insulin receptor substrate 1 . ^^^ Insulin treatment of adipocytes causes the rapid phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) on tyrosine . ^^^ Moreover , the purified Tyr ( P ) form of IRS 1 , either isolated from 3T3 L 1 adipocytes or obtained by phosphorylation of the recombinant protein with the insulin receptor , markedly stimulated the activity of purified rat liver PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activation of the SH 2 containing protein tyrosine phosphatase , SH PTP 2 , by phosphotyrosine containing peptides derived from insulin receptor substrate 1 . ^^^ The cytoplasmic insulin receptor substrate 1 ( IRS 1 ) , which is multiply phosphorylated in vivo on tyrosine residues , is a known binding protein for the tandem src homology 2 ( SH 2 ) domain containing protein tyrosine phosphatase , SH PTP 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Dephosphorylation of insulin receptor substrate 1 by the tyrosine phosphatase PTP2C . ^^^ The phosphotyrosine ( Tyr ( P ) ) form of insulin receptor substrate 1 ( IRS 1 ) is a key component in insulin signaling . ^^^ In the present study , we examined the activity of this enzyme and of a truncated form lacking the SH 2 domains ( delta PTP2C ) toward IRS 1 and also toward the cytoplasmic domain of the insulin receptor . ^^^ Tyr ( P ) IRS 1 was prepared by phosphorylation of recombinant IRS 1 with recombinant cytoplasmic insulin receptor kinase ( CIRK ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although no substrates specific for the insulin receptor were detected , phosphorylation of a 170 kilodalton ( kDa ; IRS 1 ) and a 70 kDa protein was 10 times more sensitive to insulin than to IGF 1 ( EC 50 = 1 . 5 2 . 5 vs . 14 23 nM ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regulation of insulin receptor , insulin receptor substrate 1 and phosphatidylinositol 3 kinase in 3T3 F442A adipocytes . ^^^ Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate insulin receptor substrate 1 ( IRS 1 ) , which in turn associates with and activates the enzyme phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^ The differentiation of 3T3 F442A cells was characterized by a 13 fold increase in insulin receptor protein , a 9 fold increase in IRS 1 , and a 10 and 4 . 5 fold increase in their insulin stimulated phosphorylation , respectively . ^^^ The expression of insulin receptor mRNA was unchanged , but the expression of IRS 1 mRNA was decreased by approximately 75 % after dexamethasone . ^^^ Chronic treatment with 100 nM insulin induced a time and dose dependent decrease in insulin receptor and IRS 1 protein levels reaching a nadir of 34 + / 5 % ( P < 0 . 005 ) and 39 + / 5 % ( P < 0 . 01 ) of control levels after 24 h , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Potent activation of phosphatidylinositol 3 ' kinase by simple phosphotyrosine peptides derived from insulin receptor substrate 1 containing two YMXM motifs for binding SH 2 domains . ^^^ The phosphotyrosine form of the major substrate for the insulin receptor tyrosine kinase , insulin receptor substrate 1 ( IRS 1 ) , associates with and activates the enzyme phosphatidylinositol 3 ' kinase ( PtdIns 3 ' kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This neutralization resulted in a marked increase in insulin stimulated autophosphorylation of the IR , as well as phosphorylation of insulin receptor substrate 1 ( IRS 1 ) in muscle and fat tissues of the fa / fa rats , restoring them to near control ( lean ) levels . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The 145 kDa protein , which appears , from antiphosphotyrosine blots of two dimensional O ' Farrell gels , to exist in four different phosphorylation states following cytokine stimulation ( with isoelectric points ranging from 7 . 2 to 7 . 8 ) , does not appear to be immunologically related to the beta subunit of the interleukin 3 receptor , c Kit , BCR , ABL , JAK 1 , JAK 2 , Sos 1 , eps 15 , or insulin receptor substrate 1 protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Similar insulin stimulated receptor autophosphorylation was observed in all three lines , along with a nearly identical increase in the association of phosphorylated insulin receptor substrate 1 with endogenous PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation and immunoblotting experiments using antibodies against the regulatory subunit of PI 3 K ( p 85 ) , phosphotyrosine , and insulin receptor alpha and beta subunits demonstrate that lovastatin inhibits the association of p 85 with tyrosine phosphorylated insulin receptor substrate 1 and the beta subunit of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , we demonstrate the association of the phosphorylated Leu 323 mutant receptor with insulin receptor substrate 1 and with phosphatidylinositol 3 kinase . ^^^ These findings indicate that insulin binding is not required for phosphorylation of the Leu 323 mutant receptor , that the phosphorylation of the Leu 323 mutant receptor occurs by an intermolecular transphosphorylation mechanism , and , finally , that the Leu 323 mutant receptor , once phosphorylated , can associate with insulin receptor substrate 1 and phosphatidylinositol 3 kinase . . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , unlike UR 2 protein , mutant TM 1 protein becomes glycosylated , is differentially phosphorylated , and fails to induce tyrosine phosphorylation of a 88 kDa protein and a major substrate of insulin receptor , insulin receptor substrate 1 . ^^^ The TM 1 protein is unable to associate with phosphatidylinositol 3 kinase and fails to promote association of insulin receptor substrate 1 with phosphatidylinositol 3 kinase . ^^^ The mutant defines a signaling pathway including phosphatidylinositol 3 kinase , insulin receptor substrate 1 , and possibly an 88 kDa protein that does not overlap the Ras pathway and is important for full transforming and mitogenic potency of 5 ros protein tyrosine kinase . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association of insulin receptor substrate 1 with integrins . ^^^ Insulin stimulation was found to promote association of the alpha 5 beta 3 integrin ( a vitronectin receptor ) with insulin receptor substrate 1 ( IRS 1 ) , an intracellular protein that mediates insulin signaling by binding other signaling molecules , including growth factor receptor bound protein 2 ( Grb 2 ) and phosphatidylinositol 3 ' kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Identification of a 190 kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate 1 . ^^^ We identified pp 190 as a novel substrate for insulin receptor kinase ( IRS 2 ) , which can bind both PI 3 kinase and Ash / Grb2 , and whose tyrosine phosphorylation is specifically induced in IRS 1 deficient mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cr ( 6 ) pretreatment also inhibited the insulin induced tyrosine phosphorylation of the major substrate of the insulin receptor kinase , insulin receptor substrate 1 , and its subsequent association with the 85 kDa regulatory subunit ( p 85 ) of phosphatidylinositol 3 ' kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 tyrosine phosphorylation followed the kinetics of IRK activation in ENs not PM and a hypoglycemic response similar to that achieved with a pharmacological dose of insulin ensued . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor phosphorylation , insulin receptor substrate 1 phosphorylation , and phosphatidylinositol 3 kinase activity are decreased in intact skeletal muscle strips from obese subjects . ^^^ In the lean subjects , tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) , measured by immunoblotting with anti phosphotyrosine antibodies , was significantly increased by insulin at all time points . ^^^ In addition , the obese subjects had a lower abundance of the insulin receptor , IRS 1 , and the p 85 subunit of PI 3 kinase ( 55 , 54 , and 64 % of nonobese , respectively ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphotyrosine dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non SH 2 domain . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These observations suggest that paxillin serves as an adapter protein , similar to insulin receptor substrate 1 , and that pp125FAK may regulate the formation of signaling complexes by directing the phosphorylation of paxillin on tyrosine . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In all three cell types insulin caused the rapid tyrosine phosphorylation of a 160 kD protein , which was shown not to be the insulin receptor substrate 1 ( IRS 1 ) and may be the recently described IRS 2 , as well as that of a 100 kD polypeptide , which is probably a mixture of the beta subunits of the insulin and insulin like growth factor 1 receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both glucose and insulin stimulate the tyrosine phosphorylation of the insulin receptor substrate ( IRS ) IRS 1 and increase by two to fivefold the rapid association of IRS 1 with the 85 kDa alpha subunit of the phosphatidylinositol 3 kinase , as determined by co immunoprecipitation assays . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Non SH 2 domains within insulin receptor substrate 1 and SHC mediate their phosphotyrosine dependent interaction with the NPEY motif of the insulin like growth factor 1 receptor . ^^^ Insulin receptor substrate 1 ( IRS 1 ) and SHC become rapidly phosphorylated upon tyrosines after insulin like growth factor 1 receptor ( IGFIR ) activation . ^^^ We conclude that the interactions of SHC and IRS 1 with the IGFIR are similar to those which we have previously defined with the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association of insulin receptor substrate 1 with simian virus 40 large T antigen . ^^^ Mouse embryo cells expressing a wild type number of insulin like growth factor 1 receptors ( IGF IR ) ( W cells ) can be transformed either by simian virus 40 large T antigen ( SV 40 T ) or by overexpressed insulin receptor substrate 1 ( IRS 1 ) , singly transfected . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here , we describe p55PIK , a new regulatory subunit that was isolated by screening expression libraries with tyrosine phosphorylated insulin receptor substrate 1 ( IRS 1 ) . p55PIK is composed of a unique 30 residue NH 2 terminus followed by a proline rich motif and two Src homology 2 ( SH 2 ) domains with significant sequence identify to those in p 85 . p55PIK mRNA is expressed early during development , remains abundant in adult mouse brain and testis tissue , and is detectable in adult adipocytes and heart and kidney tissues . p55PIK forms a stable complex with p 110 , and it associates with IRS 1 during insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Effect of ethanol on p 36 protein kinase substrate and insulin receptor substrate 1 expression and tyrosyl phosphorylation in human hepatocellular carcinoma cells . ^^^ Growth factor receptor kinases , such as IN and EGF , phosphorylate insulin receptor substrate ( IRS 1 ) and p 36 protein kinase substrate , respectively , on tyrosine residues . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The role of the NPXY motif in the insulin receptor in tyrosine phosphorylation of insulin receptor substrate 1 and Shc . ^^^ The insulin receptor phosphorylates insulin receptor substrate 1 ( IRS 1 ) and Shc on tyrosine residues , both of which associate with the protein abundant Src homology / growth factor receptor bound protein 2 ( ASH / GRB2 ) leading to p21ras activation . ^^^ Juxtamembrane Tyr 960 of the insulin receptor required for tyrosine phosphorylation of both IRS 1 and Shc is contained in the NPXY motif , which is also present in other tyrosine kinase receptors and oncogene products . ^^^ These data suggest that the NPXY motif in the insulin receptor is important for tyrosine phosphorylation of both IRS 1 and Shc as well as subsequent signaling . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is the principle cellular substrate for insulin and insulin like growth factor 1 ( IGF 1 ) receptor signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Consistent with the known requirement for 4PS or insulin receptor substrate 1 ( IRS 1 ) in IL 4 mediated mitogenesis , activation of STF IL 4 in 32D cells is not sufficient for IL 4 inducible c myc expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Effect of glucagon on insulin receptor substrate 1 ( IRS 1 ) phosphorylation and association with phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^ In the present study we have examined the levels and phosphorylation state of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) as well as the association between IRS 1 and phosphatidylinositol 3 kinase ( PI 3 kinase ) in the liver and muscle of rats treated with glucagon . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interleukin 9 induces tyrosine phosphorylation of insulin receptor substrate 1 via JAK tyrosine kinases . ^^^ In addition to the activation of JAK 1 and JAK 3 tyrosine kinases , IL 9 , unlike most hematopoietic cytokines but similar to IL 4 , induces the tyrosine phosphorylation of a 170 kDa protein that is related to the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In order to characterize the potential site ( s ) of action of PTP1B in insulin signaling , we also determined that insulin stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation were increased 2 . 2 and 2 . 0 fold , respectively , and that insulin stimulated receptor kinase activity toward an exogenous peptide substrate was increased by 57 % in the PTP1B antibody loaded cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , dexamethasone decreased both tyrosine phosphorylation and expression of insulin receptor substrate 1 ( IRS 1 ) and IRS 1 associated phosphatidylinositol 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although the in situ phosphorylation of insulin receptor substrate 1 and p 60 by this receptor was inhibited by prior stimulation of protein kinase C alpha , the in vitro tyrosine phosphorylation of these two substrates by this receptor was not decreased by prior stimulation of the protein kinase C alpha in the cells that served as a source of the substrates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Distinct modes of interaction of SHC and insulin receptor substrate 1 with the insulin receptor NPEY region via non SH 2 domains . ^^^ Insulin receptor substrate 1 ( IRS 1 ) and src homology and collagen protein ( SHC ) are signaling proteins which are rapidly phosphorylated on tyrosines after insulin receptor ( IR ) activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Previous studies have demonstrated that insulin receptor tyrosine kinase activity and subsequent phosphorylation of insulin receptor substrate 1 ( IRS 1 ) contribute to mediating the effect of insulin on glucose transport . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Angiotensin 2 induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3 kinase in rat heart . ^^^ We have investigated whether angiotensin 2 ( AII ) is able to induce insulin receptor substrate 1 ( IRS 1 ) phosphorylation and its association with phosphatidylinositol 3 kinase ( PI 3 kinase ) in the rat heart in vivo . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Identification by mutation of the tyrosine residues in the insulin receptor substrate 1 affecting association with the tyrosine phosphatase 2C and phosphatidylinositol 3 kinase . ^^^ The insulin receptor substrate 1 ( IRS 1 ) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The association of the src homology 2 ( SH 2 ) domain containing tyrosine phosphatase ( SH PTP 2 ) with the activated epidermal growth factor ( EGF ) and platelet derived growth factor receptors , as well as the insulin receptor substrate 1 and growth factor receptor bound protein 2 and its intrinsic tyrosine phosphatase activity suggests an important role for this phosphatase in signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced egr 1 expression in Chinese hamster ovary cells is insulin receptor and insulin receptor substrate 1 phosphorylation independent . ^^^ Insulin ' s effects primarily are initiated by insulin binding to its plasma membrane receptor and the sequential tyrosine phosphorylation of the insulin receptor and intracellular substrates , such as insulin receptor substrate 1 ( IRS 1 ) . ^^^ The present study compared the levels of insulin binding , insulin receptor and IRS 1 tyrosine phosphorylation , and phosphatidylinositol 3 ' kinase activity to immediate early gene c fos and egr 1 mRNA expression in Chinese hamster ovary ( CHO ) cells expressing only neomycin resistant plasmid ( CHONEO ) , overexpressing wild type human insulin receptor ( CHOHIRc ) or ATP binding site mutated insulin receptors ( CHOA1018K ) . ^^^ Insulin binding in CHONEO cells was markedly lower than that in other cell types . 10 nM insulin significantly increased tyrosine phosphorylation of insulin receptor and IRS 1 in CHOHIRc cells . ^^^ Phosphorylation of insulin receptor and IRS 1 in CHONEO and CHOA1018K cells was not detected in the presence or absence of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Combination of insulinomimetic agents H2O2 and vanadate enhances insulin receptor mediated tyrosine phosphorylation of IRS 1 leading to IRS 1 association with the phosphatidylinositol 3 kinase . ^^^ To analyze the mechanism of action of the insulinomimetic agents H2O2 , vanadate , and pervanadate ( H2O2 and vanadate ) , CHO cells or CHO cells that overexpress wild type or mutant insulin receptor and / or the insulin receptor substrate ( IRS 1 ) were used . ^^^ H2O2 or vanadate treatment alone had little or no effect on tyrosine phosphorylation of cellular proteins ; however , pervanadate treatment dramatically enhanced tyrosine phosphorylation of a number of proteins including the insulin receptor and IRS 1 . ^^^ However , the insulin receptor and IRS 1 coimmunoprecipitate from insulin treated but not from pervanadate treated cells . ^^^ Pervanadate induced tyrosine phosphorylation of the insulin receptor led to an increase in insulin receptor tyrosine kinase activity toward IRS 1 in vivo and IRS 1 peptides in vitro equal to that induced by insulin treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interferon alpha engages the insulin receptor substrate 1 to associate with the phosphatidylinositol 3 ' kinase . ^^^ Interferon alpha ( IFN alpha ) induces rapid tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) , a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 ( SH 2 ) domains of various signaling proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin , but not dinitrophenol , caused tyrosine phosphorylation of several polypeptides , including the insulin receptor substrate 1 and mitogen activated protein kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance : interactions between obesity and a common variant of insulin receptor substrate 1 . ^^^ We previously discovered two aminoacid polymorphisms in codons 513 and 972 of the protein insulin receptor substrate 1 ( IRS 1 ) , which is important in cellular insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signaling is known to proceed through the insulin receptor to the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SHPTP 2 was also associated with tyrosine phosphorylated insulin receptor substrate 1 , but this only accounted for < 2 % of the total immunoreactive SHPTP 2 protein . ^^^ Similarly , only a small fraction of the total amount of tyrosine phosphorylated insulin receptor substrate 1 ( < 4 % ) was associated with SHPTP 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The constitutively active tyrosine kinase of this mutant was verified by promoted tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) in the absence of IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Previous studies suggested the involvement of the insulin receptor substrate 1 ( IRS 1 ) in the IL 4 signal transduction pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ethanol inhibits insulin receptor substrate 1 tyrosine phosphorylation and insulin stimulated neuronal thread protein gene expression . ^^^ The effects of ethanol on NTP gene expression were associated with impaired insulin mediated tyrosine phosphorylation of both the insulin receptor beta subunit and the insulin receptor substrate 1 ( IRS 1 ) , resulting in decreased association of phosphatidylinositol 3 kinase with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Transforming potential of the insulin receptor substrate 1 . ^^^ The role of the insulin receptor substrate 1 ( IRS 1 ) in cellular transformation was studied in R cells , which are 3T3 like fibroblasts derived from mouse embryos with a targeted disruption of the insulin like growth factor 1 receptor gene . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Two of the insulin receptor substrates have been identified as IRS 1 and Shc . ^^^ IRS 1 is phosphorylated at several sites by the insulin receptor , and acts as a docking protein by associating several SH 2 containing proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 rescues insulin action in CHO cells expressing mutant insulin receptors that lack a juxtamembrane NPXY motif . ^^^ Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 ( IRS 1 ) and Shc by the activated insulin receptor ( IR ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Dexamethasone treatment caused an increase in in vivo IR autophosphorylation and insulin receptor substrate 1 ( IRS 1 ) phosphorylation both early events in the insulin signaling pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Role of p 85 subunit of phosphatidylinositol 3 kinase as an adaptor molecule linking the insulin receptor to insulin receptor substrate 1 . ^^^ After insulin stimulation of cells , signaling complexes are formed , containing the insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Amino acid polymorphisms of the insulin receptor substrate 1 in Japanese noninsulin dependent diabetes mellitus . ^^^ By using polymerase chain reaction restriction length polymorphism and polymerase chain reaction single strand conformation polymorphism analysis , we screened 283 Japanese subjects [ 226 noninsulin dependent diabetes mellitus ( NIDDM ) , 12 impaired glucose tolerance , and 45 normal controls ] for 2 amino acid polymorphisms , Ala513Pro and Gly972Arg , of the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) , an endogenous substrate for the insulin receptor tyrosine kinase , mediates many or all of the metabolic actions of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this report , we describe the kinetic parameters and binding affinities of SH 2 domains of p 85 toward short phosphotyrosine containing peptides with the amino acid sequence motif YMXM , derived from a major insulin receptor substrate , IRS 1 , by using real time biospecific interaction analysis ( BIAcore ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After insulin treatment of these cells , pp 60 , as well as the 160 kDa insulin receptor substrate 1 ( IRS 1 ) , were found to be associated with the enzyme phosphatidylinositol 3 kinase ( PtdIns 3 kinase ) in separate complexes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Glucocorticoid regulation of insulin receptor and substrate IRS 1 tyrosine phosphorylation in rat skeletal muscle in vivo . ^^^ To test the hypothesis that glucocorticoid induced insulin resistance might originate from abnormalities in insulin receptor signaling , we investigated the effects of glucocorticoids on in vivo tyrosine phosphorylation of the insulin receptor and the insulin receptor substrate IRS 1 in rat skeletal muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Lowest affinity ( 80 to 300 fold lower ) was observed with phosphopeptides corresponding to phosphorylated tyrosines of GTPase activating protein , insulin receptor substrate 1 , and SH 2 domain containing protein tyrosine phosphatase 1 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 mediates insulin and insulin like growth factor 1 stimulated maturation of Xenopus oocytes . ^^^ In most mammalian cell types , this results in rapid tyrosine phosphorylation of a high molecular weight substrate termed insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Substitution of the erbB 2 oncoprotein transmembrane domain activates the insulin receptor and modulates the action of insulin and insulin receptor substrate 1 . ^^^ This activity results in an increase in the level of insulin receptor substrate 1 phosphorylation but a down regulation in insulin receptor substrate 1 protein and desensitization to insulin stimulation of glycogen synthesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , which in turn binds to and activates phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Modulation of insulin receptor , insulin receptor substrate 1 , and phosphatidylinositol 3 kinase in liver and muscle of dexamethasone treated rats . ^^^ Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate , insulin receptor substrate 1 ( IRS 1 ) , which in turn associates with phosphatidylinositol 3 kinase ( PI 3 kinase ) , thus activating the enzyme . ^^^ In the present study we have examined the levels and phosphorylation state of the insulin receptor and IRS 1 , as well as the association / activation between IRS 1 and PI 3 kinase in the liver and muscle of rats treated with dexamethasone . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin induced association of PI 3 kinase activity with insulin receptor sustrate 1 ( IRS 1 ) was inhibited in both wortmannin treated cells and delta p 85 overexpressing cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The ability of the drosophila cytoplasmic domain to mediate the tyrosine phosphorylation of insulin receptor substrate 1 , stimulate cell proliferation , and activate MAP kinase was found to be indistinguishable from that of the human IR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A portion of the insulin receptor substrate 1 gene in 30 NIDDM subjects and in normal control subjects was also screened for mutations . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Whereas insulin receptor substrate 1 was weakly detected , insulin increased 5 . 5 + / 1 . 5 fold ( mean + / SD ) PtdIns 3 ' kinase activity in receptor immunoprecipitates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulation of receptor tyrosine kinase activity was only slightly decreased in muscle of young obese mice , whereas insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation was blunted . ^^^ In adipocytes from young obese mice , insulin ' s stimulatory effect on the phosphorylation of insulin receptor beta subunit , pp 60 , and an exogenous substrate was normal , whereas IRS 1 tyrosine phosphorylation was markedly depressed . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found that , compared to wild type insulin and IGF 1 receptors , the chimeric receptor showed a decrease in ( a ) autophosphorylation , ( b ) tyrosine kinase activity towards insulin receptor substrate 1 and the insulin receptor ( 1142 1158 ) peptide , and ( c ) the ability to activate phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The normal heterotetrameric receptors possess kinase activity in vivo leading to tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and its association with the p 85 regulatory subunit of phosphatidyl inositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The pleckstrin homology domain in insulin receptor substrate 1 sensitizes insulin signaling . ^^^ The NH 2 terminus of insulin receptor substrate 1 ( IRS 1 ) contains a pleckstrin homology ( PH ) domain . ^^^ Overexpression of the insulin receptor in 32DIR cells , however , restores tyrosine phosphorylation of IRS 1 delta PH and rescues insulin responses including mitogenesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Antibodies raised against the entire insulin receptor substrate 1 ( IRS 1 ) protein immunoprecipitated p 170 much less efficiently than they did IRS 1 from 3T3 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Similarly , insulin failed to stimulate tyrosyl phosphorylation of receptor beta subunits or insulin receptor substrate 1 ( IRS 1 ) in transgenic muscle . ^^^ We conclude that ( 1 ) transgenic expression of kinase defective insulin receptors exerts dominant negative effects at the level of receptor auto phosphorylation and kinase activation ; ( 2 ) insulin receptor tyrosine kinase activity is required for in vivo insulin stimulated IRS 1 phosphorylation , IRS 1 associated PI 3 kinase activation , phosphorylation of mitogen activated protein kinase , and c fos gene induction in skeletal muscle ; ( 3 ) hybrid receptor formation is likely to contribute to the in vivo dominant negative effects of kinase defective receptor expression . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates signaling reactions that include insulin receptor autophosphorylation and tyrosine kinase activation , insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , and phosphatidylinositol 3 kinase ( PI 3 kinase ) activation . ^^^ Insulin increased tyrosine phosphorylation of the insulin receptor and IRS 1 , whereas contraction alone had no effect . ^^^ Contraction alone had little effect on PI 3 kinase activity , but contraction markedly blunted the insulin stimulated activation of IRS 1 and insulin receptor immunoprecipitable PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Alternative splicing of insulin receptor mRNA and gene expression of insulin receptor , IRS 1 and MAP kinase isoforms were examined in skeletal muscle of trained and sedentary rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Following insulin stimulation , SHPTP 2 , a non transmembrane protein tyrosine phosphatase , associates with insulin receptor substrate 1 via its Src homology 2 ( SH 2 ) domains . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth hormone , interferon gamma , and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate 1 . ^^^ In the present study , GH is shown to stimulate tyrosyl phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , the principle substrate of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular cloning of an amphibian insulin receptor substrate 1 like cDNA and involvement of phosphatidylinositol 3 kinase in insulin induced Xenopus oocyte maturation . ^^^ An insulin receptor substrate 1 ( IRS 1 ) like cDNA was isolated from a Xenopus ovary cDNA library by low stringency hybridization using rat IRS 1 cDNA as a probe . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 gene mutations in NIDDM ; implications for the study of polygenic disease . ^^^ Variations in the coding regions of the insulin receptor substrate 1 ( IRS 1 ) gene have recently been suggested to contribute to the susceptibility of non insulin dependent diabetes mellitus ( NIDDM ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These proteins were found to be associated with the insulin receptor substrate 1 most likely through src homology ( SH 2 ) domains of these proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A mutant insulin receptor induces formation of a Shc growth factor receptor bound protein 2 ( Grb 2 ) complex and p21ras GTP without detectable interaction of insulin receptor substrate 1 ( IRS 1 ) with Grb 2 . ^^^ Insulin receptors induce p21ras GTP formation by two possible mechanisms : tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and its subsequent association with Grb 2 , or Shc phosphorylation and its subsequent association with Grb 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin causes rapid insulin receptor autophosphorylation , receptor endocytosis , and phosphorylation of its principle substrate ( IRS 1 ) . ^^^ The phosphorylation state of IRS 1 in the IM parallels that of the insulin receptor , but cytosolic IRS 1 phosphorylation remains constant . ^^^ The dephosphorylation of the insulin receptor and IRS 1 in the IM appears to be a concerted process , possibly mediated by the same enzyme . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor tyrosine kinase activity accounts for tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , but the serine kinase ( s ) responsible for serine phosphorylation of IRS 1 is ( are ) unknown . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These features include receptor autophosphorylation , phosphorylation of insulin receptor substrate 1 , and activation of Ras and phosphatidylinositol 3 kinase ( PI3K ) . ^^^ In response to IGF 1 , insulin receptor substrate 1 was tyrosine phosphorylated and formed a complex with the PI3K heterodimer that consists of a p 85 regulatory subunit and a p 110 catalytic subunit . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
WT and c ' 973 EGFR exhibited ligand dependent tyrosine kinase activity and stimulated mitogen activated protein kinase activity equivalently ; neither phosphorylated insulin receptor substrate 1 . ^^^ EGF did not stimulate tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor substrate ( IRS ) 1 in intact cells by the mutant IGF 1 receptors was similar to the level of IRS 1 phosphorylation seen in the parental NIH 3T3 cells , but there was no obvious dominant negative effect on IRS 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association between GRB2 / Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal regulated kinases by interleukin 4 : implications for Ras activation by insulin . ^^^ Insulin receptor substrate 1 ( IRS 1 ) mediates the activation of a variety of signaling pathways by the insulin and insulin like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH 2 domains . ^^^ We and others have shown that in response to insulin stimulation IRS 1 binds GRB2 / Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A peptide containing acidic residues N terminal to the substrate Tyr as well as the Tyr Met Xaa Met motif of the insulin receptor substrate 1 had a Km value of 15 microM , the lowest value for a synthetic peptide reported to date . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth hormone stimulates the tyrosine phosphorylation of the insulin receptor substrate 1 and its association with phosphatidylinositol 3 kinase in primary adipocytes . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is tyrosine phosphorylated in response to insulin resulting in association with and activation of phosphatidylinositol 3 kinase ( PI 3 kinase ) , thereby initiating some of the effects of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphatidylinositol 3 ' kinase ( PI 3 ' kinase ) is activated in insulin stimulated cells by the binding of the SH 2 domains in its 85 kDa regulatory subunit to insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , the insulin receptor does not bind Grb 2 directly but rather induces the tyrosine phosphorylation of two proteins , insulin receptor substrate 1 and Shc , that bind the Grb2 / Sos complex . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The oxazolidinedione CP 92 , 768 2 partially protects insulin receptor substrate 1 from dexamethasone down regulation in 3T3 L 1 adipocytes . ^^^ We selected the oxazolidinedione CP 92 , 768 2 ( 5 [ 2 [ ( 5 methyl 2 phenyl 4 oxazolyl ) methyl ] 5 benzofuranyl methyl ] 2 , 4 oxazolidinedione ) to determine whether these agents could reverse the dexamethasone induced down regulation of IRS 1 , the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin and dexamethasone regulate insulin receptors , insulin receptor substrate 1 , and phosphatidylinositol 3 kinase in Fao hepatoma cells . ^^^ Insulin rapidly stimulates tyrosine kinase activity of its receptor , resulting in phosphorylation of the cytosolic substrate , insulin receptor substrate 1 ( IRS 1 ) , which , in turn , associates with phosphatidylinositol 3 kinase ( PI 3 kinase ) , thus activating the enzyme . ^^^ Prolonged insulin treatment induced a time and dose dependent decrease in insulin receptor and IRS 1 protein levels , reaching nadirs of 40 + / 4 % ( P < 0 . 01 ) and 15 + / 6 % ( P < 0 . 005 ) of control levels , respectively , after 24 h with 100 nM insulin . ^^^ When cells were exposed to both insulin and dexamethasone , the effect of insulin to reduce insulin receptor and IRS 1 levels and insulin stimulated IRS 1 phosphorylation dominated . ^^^ These data suggest that regulation of the insulin receptor , IRS 1 , and PI 3 kinase contributes significantly to the insulin resistance induced by chronic hyperinsulinemia , but that glucocorticoid induced insulin resistance is located beyond these early steps in insulin action . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The expression of the insulin receptor substrate 1 ( IRS 1 ) and analysis of its mechanism ] . ^^^ IRS 1 ( insulin receptor substrate 1 ) is a major substrate for the insulin receptor tyrosine kinase . ^^^ IRS 1 ( insulin receptor substrate 1 ) is a major substrate for the insulin receptor tyrosine kinase . ^^^ After phosphorylation by the insulin receptor , IRS 1 binds to the specific molecules which possess SH 2 ( src homology 2 ) domain such as 85 kDa subunit of phosphatidylinositol 3 kinase and may mediate insulin signals . ^^^ In animal models of insulin resistance , phosphorylation of IRS 1 was mainly regulated by the insulin receptor tyrosine kinase both in liver and muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The role of tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) was studied utilizing parental CHO cells or CHO cells that overexpress IRS 1 , the insulin receptor , or both IRS 1 and the insulin receptor . ^^^ Effect of phosphotyrosyl IRS 1 level and insulin receptor tyrosine kinase activity on insulin stimulated phosphatidylinositol 3 , MAP , and S 6 kinase activities . ^^^ However , insulin sensitivity of the MAP and S 6 kinases and maximal insulin stimulated S 6 kinase activity was not changed by a twofold increase in phosphotyrosyl IRS 1 , but an increase was observed with insulin stimulated receptor autophosphorylation and kinase activity in CHO / IR cells which led to a tenfold increase in insulin receptor autophosphorylation and a fourfold increase in IRS 1 tyrosine phosphorylation . ^^^ Thus , these three kinase activities may be differentially coupled to the activation of the insulin receptor kinase activity via IRS 1 and other possible cellular substrates . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
On a cellular level , TNF alpha is a potent inhibitor of the insulin stimulated tyrosine phosphorylations on the beta chain of the insulin receptor and insulin receptor substrate 1 , suggesting a defect at or near the tyrosine kinase activity of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These results suggest that the ErbB 3 protein can be phosphorylated on tyrosine residues by a cross phosphorylation mechanism and that the phosphorylated ErbB 3 protein can couple other growth factor receptor protein tyrosine kinases to the PI 3 kinase pathway in a manner similar to the insulin receptor substrate 1 protein . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No gross changes in the tyrosine phosphorylation state of the insulin receptor substrate 1 were detected in insulin stimulated CHO . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SH PTP 2 is a nontransmembrane human protein tyrosine phosphatase that contains two Src homology 2 ( SH 2 ) domains and binds to insulin receptor substrate 1 ( IRS 1 ) via these domains in response to insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The specificity of the fusion protein was examined by in vitro precipitation experiments , which showed that the SH 2 domain of p 85 can independently associate with both insulin receptor substrate 1 and the insulin receptor itself in the absence of detectable binding to other phosphoproteins . ^^^ Microinjection of the SH 2 domain fusion protein also inhibited insulin signaling in these cells , suggesting that association of p 85 with insulin receptor substrate 1 is a key element in insulin mediated cell cycle progression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interactive roles of Ras , insulin receptor substrate 1 , and proteins with Src homology 2 domains in insulin signaling in Xenopus oocytes . ^^^ Insulin receptor substrate 1 ( IRS 1 ) serves as the major immediate substrate of insulin / insulin like growth factor ( IGF ) 1 receptors and following tyrosine phosphorylation binds to specific Src homology 2 ( SH 2 ) domain containing proteins including the p 85 subunit of phosphatidylinositol ( PI ) 3 kinase and GRB 2 , a molecule believed to link IRS 1 to the Ras pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 mediates phosphatidylinositol 3 ' kinase and p70S6k signaling during insulin , insulin like growth factor 1 , and interleukin 4 stimulation . ^^^ Insulin Receptor Substrate 1 ( IRS 1 ) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin , IGF 1 , and interleukin 4 ( IL 4 ) . ^^^ Expression of the insulin receptor alone partially mediates insulin stimulated microtubule associated protein ( MAP ) kinase activation , and the addition of IRS 1 enhances this effect ( Myers , M . ^^^ Expression of IRS 1 alone in 32D cells mediates the stimulation of p70S6k by insulin , IGF 1 , or IL 4 ; addition of insulin receptor to these cells increases the sensitivity of the insulin response . ^^^ In contrast , full insulin stimulation of PI 3 ' kinase requires both the insulin receptor and IRS 1 , suggesting that a high level of IRS 1 phosphorylation is required for insulin stimulated PI 3 ' kinase activation , whereas a low level of IRS 1 tyrosine phosphorylation transmits an essential signal to p70S6k . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The roles of the alpha and beta isoforms of phosphatidylinositol ( PI ) 3 ' kinase p 85 regulatory subunit were studied with isoform specific antisera in three model systems in which the insulin receptor mediates rapid phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^ Insulin receptor signaling stimulated the association of IRS 1 with p 85 alpha protein , and p 85 alpha associated PI 3 kinase activity in 3T3 L 1 adipocytes , and in transfected Chinese hamster ovary cells ( CHO T ) and COS 1 cells expressing high levels of human insulin receptors . ^^^ While not detectable in 3T3 L 1 adipocytes , the p 85 beta isoform was also found to associate with IRS 1 in response to insulin receptor activation in COS 1 and CHO T cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inhibitory effect of cytochalasin D treatment on the insulin stimulation of glucose transport occurred downstream of tyrosine phosphorylation of the insulin receptor substrate 1 and of binding of phosphatidylinositol 3 kinase to the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) distribution in the rat central nervous system . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is the primary cytosolic substrate of the insulin and insulin like growth factor 1 ( IGF 1 ) receptors . ^^^ Immunoprecipitation and Western blotting experiments demonstrate the presence of substantial amounts of IRS 1 , insulin receptor , and PI 3 kinase in the brain . ^^^ In these areas most of the neurons immunoreactive for IRS 1 are also stained by either anti insulin receptor or anti IGF 1 receptor antibodies as well as PI 3 kinase antiserum . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance and growth retardation in mice lacking insulin receptor substrate 1 . ^^^ 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: P06213 and P35568 Pubmed SVM Score :0.0
LY 294002 had no effect on tyrosine phosphorylation of both the insulin receptor beta subunit and insulin receptor substrate 1 ( IRS 1 ) and did not influence the association of the p 85 subunit of PI3K with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) and Shc compete for a limited pool of Grb 2 in mediating insulin downstream signaling . ^^^ Expression of the insulin receptor substrate 1 ( IRS 1 ) or Shc cDNA resulted in both increased protein and insulin stimulated tyrosine phosphorylation of IRS 1 and Shc proteins , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin activates the insulin receptor tyrosine kinase to phosphorylate signaling molecules such as insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Characterization of the IRS 1 ( insulin receptor substrate 1 ) gene and its promoter ] . ^^^ IRS 1 ( insulin receptor substrate 1 ) is a major substrate of the insulin receptor . ^^^ IRS 1 ( insulin receptor substrate 1 ) is a major substrate of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin initiates its biological effects by activation of tyrosine kinase in the beta subunit and phosphorylates several proteins , such as insulin receptor substrate 1 ( IRS 1 ) , Shc . thereby activating phosphatidyl inositol 3 kinase activity , and ras activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Variant sequences of insulin receptor substrate 1 in patients with noninsulin dependent diabetes mellitus . ^^^ To search for genetic defects causing NIDDM , we have screened for mutations in the gene encoding insulin receptor substrate 1 ( IRS 1 ) , an intracellular protein that is phosphorylated by the insulin receptor and is thought to play an important role in mediating insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Enhancement or inhibition of insulin signaling by insulin receptor substrate 1 is cell context dependent . ^^^ Transient transfection of parental CHO cells with an insulin receptor substrate 1 ( IRS 1 ) expression plasmid enhanced insulin downstream signaling in a biphasic manner , whereas IRS 1 transfection of CHO / IR cells inhibited insulin signaling in a dose dependent fashion . ^^^ To assess the relative effects of various insulin receptor , IRS 1 , and Grb 2 levels on insulin signaling , parental CHO cells were transiently transfected with various combinations of expression plasmids encoding these proteins . ^^^ Although expression of IRS 1 resulted in a biphasic increase of insulin signaling in parental CHO cells , coexpression of IRS 1 with the insulin receptor resulted in inhibition of signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Wortmannin inhibits the PtdIns 3 kinase activity which is precipitated with antibodies against insulin receptor substrate 1 and against the alpha p 85 subunit of PtdIns 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Platelet derived growth factor receptor ( PDGF R ) phosphorylation at tyrosines 740 / 751 and insulin receptor phosphorylation of insulin receptor substrate 1 effects the recruitment and activation of phosphatidylinositol 3 OH kinase ( PI ( 3 ) K ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Further , insulin or IGF 1 treatment of SHC transfected fibroblasts leads to immunoprecipitation of SHC proteins with insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular scanning of the glycogen synthase and insulin receptor substrate 1 genes in Japanese subjects with non insulin dependent diabetes mellitus . ^^^ We studied a simple tandem repeat DNA polymorphism in the glycogen synthase gene and polymorphisms at codon 513 ( Ala > Pro ) and 972 ( Gly > Arg ) in the insulin receptor substrate 1 ( IRS 1 ) gene in 197 non insulin dependent diabetes mellitus ( NIDDM ) and 178 control subjects in Japan . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is a principal substrate of the receptor tyrosine kinase for insulin and insulin like growth factor 1 , and a substrate for a tyrosine kinase activated by interleukin 4 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Under our experimental conditions insulin and IGF 1 were not able to stimulate the phosphorylation of IRS 1 , a major substrate of the insulin receptor kinase . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulation drives the formation of a complex between tyrosine phosphorylated insulin receptor substrate 1 ( IRS 1 ) and 1 phosphatidylinositol 3 kinase ( PI 3 kinase ; ATP : 1 phosphatidyl 1D myo inositol 3 phosphotransferase , EC 2 . 7 . 1 . 137 ) , a heterodimer consisting of regulatory 85 kDa ( p 85 ) and catalytic 110 kDa ( p 110 ) subunits . ^^^ Activation of insulin receptor kinase and the tyrosine phosphorylation of IRS 1 remained unaffected . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of both the insulin receptor and its major substrates , Shc and insulin receptor substrate 1 , were unaffected by the mutant phosphatase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In response to appropriate growth factor stimulation , Syp becomes phosphorylated on tyrosine residues and associates with insulin receptor substrate 1 ( IRS 1 ) and / or the corresponding growth factor receptor via its SH 2 domains , leading to increased Syp activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In intact adipose cells , staurosporine ( 30 microM ) induced a slight ( 30 % ) decrease in the maximal insulin induced receptor autophosphorylation and a similar decrease in the tyrosine phosphorylation of pp 60 and pp 160 ( insulin receptor substrate 1 : ' IRS 1 ' ) , but was without effect on insulin binding to its receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor substrate 1 in hepatocytes : an investigation using monoclonal antibodies . ^^^ To investigate the expression and subcellular distribution of insulin receptor substrate 1 in hepatocytes , which are major targets of insulin along with muscle and adipose tissue , we obtained monoclonal antibodies by immunizing mice with a fusion protein consisting of the C terminal portion of the human insulin receptor substrate 1 and glutathione S transferase . ^^^ Using 6G5 we demonstrate a high level of expression of insulin receptor substrate 1 in liver cirrhosis hepatocytes and variable expression in hepatocellular carcinoma cells . ^^^ These results suggest that insulin receptor substrate 1 may play a role in liver regeneration during cirrhosis and that an insulin signaling cascade may be involved in hepatocarcinogenesis . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 variants in non insulin dependent diabetes . ^^^ Insulin receptor substrate 1 ( IRS 1 ) plays an important role in insulin stimulated signaling mechanisms . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kDa ( insulin receptor substrate 1 or IRS 1 ) . ^^^ IRS 1 fulfills the criteria of a direct substrate of the insulin receptor , and tyrosine phosphorylation of IRS 1 leads to another step in insulin action , i . e . , an association of phosphorylated IRS 1 with the enzyme PI 3 kinase activating this enzyme . ^^^ Using antipeptide antibodies to insulin receptor , to IRS 1 and to PI 3 kinase together with anti phosphotyrosine antibodies it is possible to study insulin stimulated insulin receptor phosphorylation , IRS 1 phosphorylation and the association / activation of IRS 1 / PI 3 kinase . 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent studies have identified several endogenous substrates of the insulin receptor kinase , including one called insulin receptor substrate 1 ( IRS 1 ) . ^^^ In this model system , activation of protein kinase C is shown to interfere with insulin receptor signalling by inhibiting tyrosine phosphorylation of IRS 1 and its subsequent binding by phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Aminoacid polymorphisms of insulin receptor substrate 1 in non insulin dependent diabetes mellitus . ^^^ Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non insulin dependent diabetes mellitus ( NIDDM ) , we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate 1 ( IRS 1 ) , a candidate gene that is ubiquitous in insulin sensitive and insulin like growth factor 1 ( IGF 1 ) sensitive tissues , including those that determine glucose production and clearance and those with regulatory effects on pancreatic beta cell function . ^^^ 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: P06213 and P35568 Pubmed SVM Score :0.0
The effect of insulin to induce membrane PI 3 kinase activity was mostly abolished , but its effects to tyrosine phosphorylate the beta subunit of the insulin receptor or other cellular substrate proteins including insulin receptor substrate 1 were not at all antagonized , by wortmannin added to the cell incubation medium . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Despite the absence of alpha 2 beta beta mut hybrids , expression of the Ile 1153 mutant receptor inhibited the ability of the delta 43 truncated receptor to mediate insulin stimulated phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , we investigated whether the Grb 2 mSOS complex associates with the insulin receptor or with insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Serine / threonine phosphorylation of insulin receptor substrate 1 modulates insulin receptor signaling . ^^^ Taken together these data suggest that serine / threonine phosphorylation of IRS 1 induced by okadaic acid reduces the ability of the insulin receptor to phosphorylate IRS 1 and to dock one of its interacting molecules , i . e . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interleukin 4 ( IL 4 ) treatment of 32D cells overexpressing insulin receptor substrate 1 ( IRS 1 ) causes prompt tyrosine phosphorylation of IRS 1 . ^^^ An IL 4 receptor region containing an insulin receptor motif is important for IL 4 mediated IRS 1 phosphorylation and cell growth . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin also stimulates a rapid increase in tyrosine phosphorylation of the 170 kDa insulin receptor substrate 1 and complex formation between the phosphorylated insulin receptor substrate 1 and the 85 kDa subunit of phosphatidylinositol 3 ' kinase . ^^^ In contrast , vanadate does not initially increase detectable phosphorylation of any proteins , including neither the insulin receptor nor the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Some of the phosphorylated proteins were identified as the beta subunit of the insulin receptor , the insulin receptor substrate 1 ( pp 185 ) , PLC gamma ( pp 145 ) , and a 100 kDa PLC gamma associated protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To explore the early signaling events that might account for this increase in responsiveness , we evaluated the tyrosine phosphorylation of the insulin receptor substrate , IRS 1 , and its subsequent association with phosphatidylinositol ( PI ) 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and She in Rat 1 fibroblasts overexpressing wild type insulin receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Binding analysis showed that the CD 28 Y ( P ) MXM motif bound to the p 85 C and N terminal SH 2 domains with an affinity comparable to that observed for PDGF R and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Despite this , phosphorylation of an in vivo insulin receptor substrate , IRS 1 , and insulin bioeffects are similar to wild type . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After insulin stimulation of rat HTC hepatoma cells overexpressing normal human insulin receptors ( IR ) , an antiserum to the p 85 subunit of phosphatidylinositol 3 kinase ( PIK ) ( alpha p 85 ) immunoprecipitated three major tyrosine phosphorylated proteins : IR , insulin receptor substrate 1 ( IRS 1 ) , and a new 62 kDa protein ( p 62 ) . ^^^ These data suggest that : 1 ) p 62 GAP associated protein is tyrosine phosphorylated after insulin stimulation of cells ; 2 ) p 62 and IRS 1 form separate complexes with p 85 ; 3 ) p 62 GAP complex may be linked to p 85 that is not bound to p 110 ; 4 ) p 85 may serve as an adaptor molecule in insulin receptor signaling , interacting with and regulating other intracellular proteins via SH 2 domains . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both inhibited the association of insulin receptor substrate 1 ( IRS 1 ) with PI 3 kinase in a cell free system and also inhibited insulin or IGF 1 induced , but not EGF induced , membrane ruffling in KB cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , we show that the hybrid receptor can phosphorylate insulin receptor substrate 1 ( IRS 1 ) in response to insulin and can be coimmunoprecipitated together with IRS 1 by anti IRS 1 antibody . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Coexpression of IRS 1 or IRS 1F 895 with the insulin receptor was required for insulin stimulated mitogenesis in 32 D cells , while expression of the insulin receptor alone was sufficient to mediate insulin stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen activated protein ( MAP ) kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Functional expression of insulin receptor substrate 1 is required for insulin stimulated mitogenic signaling . ^^^ To examine the role of the insulin receptor substrate 1 ( IRS 1 ) in mediating insulin biological responsiveness , we generated Chinese hamster ovary cell lines expressing antisense IRS 1 RNA . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Several tyrosine phosphorylation sites in the insulin receptor kinase substrate IRS 1 are predicted to be within Tyr Met 10 Met ( YMXM ) motifs , and synthetic peptides corresponding to these sequences are excellent substrates for the insulin receptor kinase in vitro ( Shoelson , S . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PI 3 kinase activity was also immunoprecipitated with antiphosphotyrosine [ alpha Tyr ( P ) ] antibodies and with antibodies raised against IRS 1 , a substrate of the insulin receptor protein tyrosine kinase that associates with and activates PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate 1 ( IRS 1 ) contains at least 11 sequence motifs that are rich in proline ( P ) , glutamic acid ( E ) , serine ( S ) , and threonine ( T ) , i . e . , PEST regions . ^^^ The insulin receptor substrate ( IRS 1 ) is a PEST protein that is susceptible to calpain degradation in vitro . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
There was about a 30 fold decrease in frequency of G 418 resistant colonies with this strategy against that using only the neo gene in the vector , and homologous recombinants were obtained at frequencies of more than 1 / 50 among G 418 resistant cells at fyn , csk , c mos , and insulin receptor substrate 1 gene loci . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Incubation of the insulin sensitive rat hepatoma Fao cells with 5 nM TNF for 1 h led to a 65 % decrease in insulin induced tyrosine phosphorylation of both the insulin receptor beta subunit and IRS 1 , its major cytosolic substrate . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These findings provide further evidence that , in response to insulin stimulation , IRS 1 acts as an SH 2 docking protein that coordinates the regulation of various different signaling pathways activated by the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A mutation in the juxtamembrane region , which disabled tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) , also prevented the chemotactic response , suggesting a possible role for IRS 1 in chemotactic signaling . ^^^ In the absence of insulin receptor , however , the presence of excess transfected IRS 1 was not sufficient to mediate chemotaxis toward insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin binds to the alpha subunit of the insulin receptor which activates the tyrosine kinase in the beta subunit and tyrosine phosphorylates the insulin receptor substrates 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is required for insulin mediated mitogenic signal transduction . ^^^ Insulin treatment of mammalian cells immediately stimulates the tyrosine phosphorylation of a cellular protein of 185 kDa referred to as pp 185 or IRS 1 ( insulin receptor substrate 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) was evaluated as a potential linking protein . ^^^ In the absence of ATP , IRS 1 did not facilitate the coupling of the phosphorylated insulin receptor to PtdIns 3 kinase . ^^^ Thus IRS 1 is unlikely to be the component in crude CHO cell lysate that couples PtdIns 3 kinase to the phosphorylated insulin receptor . ^^^ However , the addition of ATP , which allows phosphorylation of IRS 1 by the insulin receptor , also enhances the coupling of PtdIns 3 kinase to the insulin receptor . ^^^ In support of this idea , immunoprecipitates of IRS 1 from insulin treated CHO cells were found to contain both the insulin receptor and PtdIns 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Dexamethasone down regulation of insulin receptor substrate 1 in 3T3 L 1 adipocytes . ^^^ To better understand the specific effects of glucocorticoids on insulin signaling , we have characterized the effect of dexamethasone on the expression of an insulin signaling intermediate , the insulin receptor substrate 1 ( IRS 1 ) in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The SH 2 domain of GRB2 / Sem 5 binds to a number of tyrosine phosphorylated proteins , most notably the epidermal growth factor receptor , the insulin receptor substrate IRS 1 and another putative adaptor protein , Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In response to insulin stimulation , this complex bound to tyrosine phosphorylated IRS 1 ( insulin receptor substrate 1 ) and Shc . ^^^ In contrast to the activated epidermal growth factor receptor that binds the GRB 2 Sos complex directly , activation of the insulin receptor results in the interaction of GRB 2 Sos with IRS 1 and Shc , thus linking the insulin receptor to Ras signaling pathways . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Normal insulin receptor substrate 1 phosphorylation in autophosphorylation defective truncated insulin receptor . ^^^ Nevertheless , tyrosine phosphorylation of an endogenous substrate , pp 185 , and insulin receptor substrate 1 ( IRS 1 ) in CHO del 82 was comparable with that in CHO HIR . ^^^ These data suggest that : 1 ) the COOH terminal domain of the insulin receptor may play an inhibitory role in the phosphorylation of pp 185 and IRS 1 ; and 2 ) phosphorylation of substrates such as pp 185 and IRS 1 , rather than autophosphorylation of the receptor per se , correlates better with certain biological effects that were mediated by insulin , suggesting that phosphorylation of the substrates might be sufficient for transducing signals downstream . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of the insulin receptor substrate IRS 1 by casein kinase 2 . ^^^ IRS 1 , a principal substrate of the insulin receptor , is phosphorylated on serine , threonine , and tyrosine residues in a variety of tissues during insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin and IL 4 sensitivity was restored to 32D cells by expression of IRS 1 , the principal substrate of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A simple program developed to overcome this difficulty identified three proteins containing previously unrecognized PH domains ; the beta adrenergic receptor kinase ( beta ARK ) , the tecA protein kinase and the insulin receptor substrate protein IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
One of the first steps that follows insulin receptor activation is the tyrosine phosphorylation of the 160 185 kDa insulin receptor substrate IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
An example of such phosphoprotein effector coupling is provided by the association of phosphatidylinositol 3 kinase ( PI 3 kinase ) with specific phosphorylation sites within the PDGF receptor , the c Src / polyoma virus middle T antigen complex and the insulin receptor substrate IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression and phosphorylation of insulin receptor substrate 1 during rat liver regeneration . ^^^ The rat and human insulin receptor substrate 1 ( IRS 1 ) is a specific target molecule for the insulin receptor beta subunit kinase and will bind to signal transducing molecules containing Src homology 2 domains through its multiple tyrosyl phosphorylation ( TP ) sites . ^^^ TP of insulin receptor beta subunit , which enhances its kinase activity toward IRS 1 , was increased in association with TP of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The complex of tyrosyl phosphorylated IRS 1 . p85 that formed in response to insulin was localized to a very low density vesicle subpopulation that could be distinguished from vesicles containing the GLUT 4 glucose transporter and the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We investigated whether phosphatidylinositol 3 kinase ( PI3K ) is phosphorylated and whether its specific activity is increased by insulin stimulation in vivo using Fao cells and antibodies raised against the 85 kDa subunit of PI3K , insulin receptor substrate 1 ( IRS 1 ) , and phosphotyrosine ( pTyr ) . ^^^ Both IRS 1 and the insulin receptor beta subunit ( 95 kDa ) were phosphorylated on tyrosine residues by insulin stimulation and immunoprecipitated with anti pTyr . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
The major insulin receptor cellular substrate IRS 1 ( pp 185 ) has been proposed as a possible link between the insulin receptor and PtdIns 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 and proteins with SH 2 domains . ^^^ The recently discovered insulin receptor substrate , IRS 1 , provides an innovative and simple way to think about this problem : IRS 1 may mediate the control of various cellular processes by insulin . ^^^ We suspect that insulin signals are enabled when the activated insulin receptor kinase phosphorylates specific tyrosine residues in IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates association of insulin receptor substrate 1 with the protein abundant Src homology / growth factor receptor bound protein 2 . ^^^ In an anti ASH ( alpha ASH ) immunoprecipitates , we detected a 170 kDa phosphoprotein that was recognized by an anti phosphotyrosine antibody and an anti insulin receptor substrate 1 antibody ( alpha IRS 1 ) from the insulin stimulated [ 32P ] orthophosphate labeled CHO HIR cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Binding of the Ras activator son of sevenless to insulin receptor substrate 1 signaling complexes . ^^^ Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate ( IRS 1 ) and exchange of Ras bound guanosine diphosphate for guanosine triphosphate . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , in the presence of the phosphatase inhibitor , we did not observe tyrosine phosphorylation of the insulin receptor cellular substrate p 185 ( IRS 1 ) or immunoprecipitation of PI 3 kinase by antibodies to phosphotyrosine . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In CHO Y960F cells , tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , the activation of phosphatidylinositol 3 kinase in the anti phosphotyrosine and anti IRS 1 immunoprecipitates , the activation of mitogen activated protein ( MAP ) kinase , and biological actions were also impaired . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PTPases also modulate signaling through postreceptor pathways by catalyzing the dephosphorylation of cellular substrates of the insulin receptor kinase , such as IRS 1 , or other tyrosine phosphorylated proteins along the cellular cascade of insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We examined the role of 185 kDa insulin receptor substrate 1 ( IRS 1 ) and phosphatidylinositol 3 kinase ( PI 3 kinase ) in the signaling pathway of insulin stimulated GLUT 4 translocation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin and IGF 1 signaling through the insulin receptor substrate 1 . ^^^ In many cell types the most prominent phosphotyrosine ( Ptyr ) protein , in addition to the receptors themselves , is a protein of approximately 160 kD , now known as the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated oocyte maturation requires insulin receptor substrate 1 and interaction with the SH 2 domains of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin elicited 160 kDa phosphotyrosine protein in mouse adipocytes is an insulin receptor substrate 1 : identification by cloning . ^^^ Peptide sequences , obtained from this protein purified from mouse 3T3 L 1 adipocytes ( pp 160 ) , were used as the basis for cloning its cDNA , pp 160 is highly homologous to the insulin receptor substrate 1 , previously cloned from rat liver . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Human insulin receptor substrate 1 gene ( IRS 1 ) : chromosomal localization to 2q35 q36 . 1 and identification of a simple tandem repeat DNA polymorphism . ^^^ The protein designated as insulin receptor substrate 1 ( IRS 1 ) is a major substrate for the insulin receptor tyrosine kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
One protein is the major insulin receptor substrate IRS 1 and the second is the SH 2 domain containing oncogenic protein , Shc . ^^^ The interactions between GRB 2 and these two proteins require ligand activation of the insulin receptor and are mediated by the binding of the SH 2 domain of GRB 2 to phosphotyrosines on both IRS 1 and Shc . ^^^ Although GRB 2 associates with IRS 1 and Shc , it is not tyrosine phosphorylated after insulin stimulation , implying that GRB 2 is not a substrate for the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate 1 associates with the SH 2 containing phosphotyrosine phosphatase Syp . ^^^ The insulin receptor substrate 1 ( IRS 1 ) is a protein that is rapidly phosphorylated on tyrosine by the activated insulin receptor . ^^^ In combination with other findings these results indicate that IRS 1 functions as a docking protein for SH 2 domain containing proteins participating in signaling from the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Human skeletal muscle insulin receptor substrate 1 . ^^^ Insulin receptor substrate 1 is a major substrate of insulin receptor Tyr kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 may be central to phosphorylation reactions through a role in serine and threonine kinase activity . ^^^ Important roles for insulin receptor kinase , glucose transporters , insulin receptor substrate 1 , and various intracellular enzymes in the actions of insulin have been demonstrated ; nonetheless , the formulation of potential therapeutic strategies directed at particular stages of the insulin action cascade will require further elucidation of its components . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The high fat diet tended to decrease insulin receptor substrate 1 ( IRS 1 ) and phosphatidylinositol 3 ' kinase ( PI 3 kinase ) expression in epididymal fat ( 26 % decrease ; P < 0 . 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent work in our laboratory and others demonstrates the localization of PI 3 kinase to intracellular membranes via its docking to the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Further investigation as to how the signals of IGF 1 were transmitted for the biological activities demonstrated that the expression of insulin receptor substrate 1 ( IRS 1 ) is up regulated by IGF 1 treatment , while PLC gamma 1 expression is not altered by this growth factor . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A series of peptides has been prepared that reproduces the major phosphorylation sites of insulin receptor substrate 1 , a common substrate for the two receptor tyrosine kinases in vivo . ^^^ 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced phosphorylation of insulin receptors and insulin receptor substrate 1 displaces phosphorylated platelet derived growth factor receptors from binding sites on PI 3 kinase . ^^^ The p 85 regulatory subunit of PI 3 kinase binds to phosphotyrosine residues of various phosphoproteins including the platelet derived growth factor ( PDGF ) receptor , the insulin receptor , and insulin receptor substrate 1 ( IRS 1 ) . ^^^ When insulin is added , p 85 is released from phosphorylated PDGF receptors and binds to phosphorylated insulin receptors and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After stimulation with IL 4 , a 170 kDa band was primarily phosphorylated within 1 min of exposure and was identified as insulin receptor substrate 1 . ^^^ These data indicate that in colon carcinoma cells JAK 1 , JAK 2 , Tyk 2 , and insulin receptor substrate 1 are phosphorylated after IL 4 stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Effect of aging on insulin receptor , insulin receptor substrate 1 , and phosphatidylinositol 3 kinase in liver and muscle of rats . ^^^ Insulin stimulates the tyrosine kinase activity of its receptor , resulting in the phosphorylation of its cytosolic substrate , insulin receptor substrate 1 ( IRS 1 ) , which , in turn , associates with phosphatidylinositol 3 kinase ( PI 3 kinase ) , thereby activating the latter . ^^^ In the present study , we examined the levels and phosphorylation status of the insulin receptor and IRS 1 as well as the association between IRS 1 and PI 3 kinase in the liver and muscle of 2 , 5 , 12 , and 20 month old rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To evaluate the potential for regulation of the insulin receptor substrate IRS 1 , we have cloned the mouse IRS 1 gene , identified its promoter , and analyzed promoter activity in the basal state and in response to stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PI 3 kinase activity that is precipitated by anti phosphotyrosine , anti ( ) [ insulin receptor substrate 1 ( IRS 1 ) ] and anti alpha p 85 antibodies show the same level of insulin stimulated activity , approximately 0 . 5 pmol / 20 min per dish of 3T3 L 1 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Glucose and insulin induced phosphorylation of the insulin receptor and its primary substrates IRS 1 and IRS 2 in rat pancreatic islets . ^^^ Immunoprecipitation with specific antibodies demonstrated that the signal detected at 95 kDa corresponds to the beta subunit of the insulin receptor ( IR ) while the band at 165 185 kDa corresponds to the early substrates of the insulin receptor , IRS 1 and IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyr 950 together with its surrounding sequence is involved in mediating the interaction between the gag IGFR and insulin receptor substrate 1 . ^^^ The transforming potential of the gag IGFR correlates well with its ability to phosphorylate overall cellular substrates and to activate phosphatidylinositol 3 kinase via insulin receptor substrate 1 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tumor necrosis factor promotes phosphorylation and binding of insulin receptor substrate 1 to phosphatidylinositol 3 kinase in 3T3 L 1 adipocytes . ^^^ Chronic incubation of 3T3 L 1 adipocytes with tumor necrosis factor ( TNF ) induces a state of insulin resistance characterized by a diminished ability of insulin to induce phosphorylation of the beta subunit of its own receptor and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor C domain phosphopeptide inhibited the p 85 N + C SH 2 domain insulin receptor complex with an IC0 . 5 of 2 . 3 + / 0 . 35 microM , whereas a 10 residue phosphopeptide derived from the insulin receptor substrate 1 ( IRS 1 ) competed with an IC0 . 5 of 0 . 54 + / 0 . 10 microM . ^^^ Furthermore , formation of the p85 / insulin receptor complex may lead to signaling pathways independent of IRS 1 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Treatment of cultured murine adipocytes with TNF alpha was shown to induce serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and convert IRS 1 into an inhibitor of the IR tyrosine kinase activity in vitro . ^^^ IRS 1 mediated inhibition of insulin receptor tyrosine kinase activity in TNF alpha and obesity induced insulin resistance . ^^^ These results indicate that TNF alpha induces insulin resistance through an unexpected action of IRS 1 to attenuate insulin receptor signaling . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
G protein and tyrosine kinase receptor cross talk in rat aortic smooth muscle cells : thrombin and angiotensin 2 induced tyrosine phosphorylation of insulin receptor substrate 1 and insulin like growth factor 1 receptor . ^^^ The insulin like growth factor 1 triggered signaling pathway involves autophosphorylation of the beta subunit of its tyrosine kinase receptor and phosphorylation of insulin receptor substrate 1 , the latter providing binding sites for proteins with src homology 2 domains . ^^^ In rat aortic smooth muscle cells we observed that both angiotensin 2 and thrombin induced rapid tyrosine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
G ialpha 2 deficiency increases protein tyrosine phosphatase activity and attenuates insulin stimulated tyrosine phosphorylation of IRS ( insulin receptor substrate 1 ) in vivo . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The exogenous added receptors could be coupled to the intracellular effector system as shown by increased phosphorylation of the insulin receptor substrate 1 , IRS 1 , and by increased glycogen synthesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The ability of yyFH mutant IGF 1 receptors to autophosphorylate the beta subunit or phosphorylate insulin receptor substrate 1 was not significantly different from wild type type IGF 1 receptors . ^^^ Phosphorylation of insulin receptor substrate 1 by the yCF mutant receptors was not impaired . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This assay utilizes as an exogenous substrate a biotinylated peptide based on the sequence of the endogenous substrate insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Gab 1 shares amino acid homology and several structural features with IRS 1 ( insulin receptor substrate 1 ; refs 6 , 7 ) , is a substrate of the EGF and insulin receptors , and can act as a docking protein for several SH 2 containing proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We present the NMR structure of the PTB domain of insulin receptor substrate 1 ( IRS 1 ) complexed to a tyrosine phosphorylated peptide derived from the IL 4 receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased expression of insulin receptor substrate 1 in human pancreatic cancer . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a multisite docking protein implicated in mitogenic signaling following activation of the insulin and insulin like growth factor 1 receptors . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^ Proportionately , the impairment of insulin receptor substrate 1 tyrosine phosphorylation is greater than that of the insulin receptor resulting in attenuated phosphatidylinositol 3 kinase activation and mitogenic signaling . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , both autophosphorylation of the IGF 1R beta subunit ( i . e . , IGF 1R tyrosine kinase ) and the IGF 1R tyrosine kinase activity towards exogenous insulin receptor substrate 1 , a natural substrate for IGF 1R tyrosine kinase , were reduced in CRF fats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
GH also induced an increase in the PI 3 kinase activity associated with both JAK 2 and insulin receptor substrate 1 ( IRS 1 ) immunoprecipitates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To assess effects on downstream signaling , tyrosine phosphorylation of the following substrate proteins of the insulin receptor was determined : insulin receptor substrate 1 , the coupling protein Shc , focal adhesion kinase ( FAK 125 ) , and unidentified proteins of 130 kD , 60 kD . ^^^ Hyperglycemia ( 25 mM glucose ) and TNF alpha showed analogous ( > 50 % inhibition ) effects on tyrosine phosphorylation of insulin receptor substrate 1 , Shc , p 60 , and p 44 , whereas opposite effects were observed for tyrosine phosphorylation of FAK 125 , which is dephosphorylated after insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A logarithm of odds ( LOD ) score of 0 . 92 at a recombination fraction of 0 . 05 was observed for insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Systematic mapping of potential binding sites for Shc and Grb 2 SH2 domains on insulin receptor substrate 1 and the receptors for insulin , epidermal growth factor , platelet derived growth factor , and fibroblast growth factor . ^^^ Multipin peptide synthesis has been employed to produce biotinylated 11 mer phosphopeptides that account for every tyrosine residue in insulin receptor substrate 1 ( IRS 1 ) and the cytoplasmic domains of the insulin , epidermal growth factor , platelet derived growth factor and basic fibroblast growth factor receptors . ^^^ The data revealed new potential Grb 2 binding sites at Tyr 1114 ( epidermal growth factor receptor ( EGFR ) C tail ) ; Tyr 743 ( platelet derived growth factor receptor ( PDGFR ) insert region ) , Tyr 1110 from the E helix of the catalytic domain of insulin receptor ( IR ) , and Tyr 47 , Tyr 939 , and Tyr 727 in IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Unlike p 85 and Syp , which also bind to Tyr ( P ) 1322 , Grb 10 was not found to associate with insulin receptor substrate 1 . ^^^ These results suggest that Grb 10 is a novel insulin receptor interactive protein and provide direct evidence for an insulin receptor substrate 1 independent function of the insulin receptor carboxyl terminus in protein binding . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The proto oncogene product c Crk associates with insulin receptor substrate 1 and 4PS . ^^^ In 3T3 Crk cells , Crk immunoreactivity was detected in insulin receptor substrate 1 ( IRS 1 ) immunoprecipitates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Overexpression of human insulin receptor substrate 1 induces cellular transformation with activation of mitogen activated protein kinases . ^^^ The receptor insulin substrate 1 protein ( IRS 1 ) is a specific substrate for insulin receptor tyrosine kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We compared the interaction between the insulin receptor ( IR ) and the IR substrate ( IRS ) proteins IRS 1 and IRS 2 ) using the yeast two hybrid system . ^^^ The IH2PTB binds to the phosphorylated NPXY motif ( Tyr 960 ) in the activated insulin receptor , providing a specific mechanism for the interaction between the receptor and IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Consistent with this idea , complexes containing PI 3 kinase bound to insulin receptor substrate 1 ( IRS 1 ) in 3T3 L 1 adipocytes are associated with intracellular membranes ( Heller Harrison , R . , Morin , M . and Czech , M . ( 1995 ) J . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Sphingomyelinase and ceramide suppress insulin induced tyrosine phosphorylation of the insulin receptor substrate 1 . ^^^ TNF was recently shown to interfere with insulin induced tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor substrate 1 on multiple serine residues , 612 , 632 , 662 , and 731 , modulates insulin action . ^^^ In addition , this drug induces on insulin receptor substrate 1 ( IRS 1 ) a decrease in tyrosine phosphorylation , concomitantly with an increase in serine / threonine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Stimulation of the insulin receptor ( IR ) results in tyrosine phosphorylation of the intermediate molecules insulin receptor substrate 1 ( IRS 1 ) , IRS 2 , and Shc , which then couple the IR to downstream signaling pathways by serving as binding sites for signaling molecules with SH 2 domains . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3 kinase in muscle and brain . ^^^ We have identified two novel alternatively spliced forms of the p85alpha regulatory subunit of phosphatidylinositol ( PI ) 3 kinase by expression screening of a human skeletal muscle library with phosphorylated baculovirus produced human insulin receptor substrate 1 . ^^^ Both p 85 and p85 / AS53 bind to p 110 in coprecipitation experiments , but p85alpha itself appears to have preferential binding to insulin receptor substrate 1 following insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 was required by the human insulin receptor to activate PI 3 kinase and p70s6k , whereas hDIR associated with PI 3 kinase and activated p70s6k without IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Finally , Shc and insulin receptor substrate 1 ( IRS 1 ) were tyrosine phosphorylated and bound to p 80 in p 80 transformed cells . ^^^ However , mutants of p 80 that were defective for binding to and phosphorylation of Shc and insulin receptor substrate 1 could transform NIH 3T3 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor mRNA and insulin receptor substrate 1 in pancreatic islet beta cells . ^^^ Immunohistochemical analysis was insufficiently sensitive for assaying insulin receptor protein ; however , insulin receptor substrate 1 ( IRS 1 ) was readily immunolocalized in islet beta cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A structural analysis has been carried out to determine which part of the intracellular domain of the insulin receptor ( IR ) beta subunit is involved in direct interaction with the receptor substrates IRS 1 and Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Two naturally occurring mutant insulin receptors phosphorylate insulin receptor substrate 1 ( IRS 1 ) but fail to mediate the biological effects of insulin . ^^^ Anti insulin receptor substrate 1 ( IRS 1 ) immunoprecipitation followed by anti phosphotyrosine immunoblotting confirmed that this tyrosine phosphorylated protein was IRS 1 . ^^^ In contrast , CHO cells expressing an insulin receptor mutated at the ATP binding site ( Lys 1030 > Arg ) showed no insulin stimulated autophosphorylation or phosphorylation of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Codon 972 polymorphism in the insulin receptor substrate 1 gene , obesity , and risk of noninsulin dependent diabetes mellitus . ^^^ Because of the role of insulin receptor substrate 1 in insulin action , the insulin receptor substrate 1 gene is a candidate gene for noninsulin dependent diabetes mellitus ( NIDDM ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The level of insulin receptor substrate 1 ( IRS 1 ) was reduced in dexamethasone treated cells , as measured by Western blot ; however , the pattern of tyrosine phosphorylated protein subsequent to stimulation with IGF 1 ( 1 min ) was not altered . ^^^ The amount of IGF 1 induced association of insulin receptor substrate 1 and phosphatidylinositol 3 kinase was increased in steroid treated cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth inhibition signalled through the interleukin 4 / interleukin 13 receptor complex is associated with tyrosine phosphorylation of insulin receptor substrate 1 . ^^^ Induction of growth inhibition in human colorectal carcinoma cell lines by interleukin ( IL ) 4 and IL 13 was associated with the neophosphorylation of a 170 kDa cellular protein , identified as insulin receptor substrate 1 ( IRS 1 ) by immunoprecipitation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of dominant negative mutant SHPTP 2 attenuates phosphatidylinositol 3 ' kinase activity via modulation of phosphorylation of insulin receptor substrate 1 . ^^^ In response to insulin , phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , IRS 1 associated PTPase activities and phosphatidylinositol ( PI ) 3 ' kinase activities were slightly enhanced in wild type cells when compared with those in the parent cells transfected with hygromycin resistant gene alone . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A common amino acid polymorphism in insulin receptor substrate 1 causes impaired insulin signaling . ^^^ Insulin receptor substrates 1 ( IRS 1 ) is the major cytoplasmic substrate of the insulin and IGF 1 receptors . ^^^ In the present study , we have examined insulin stimulated processes in 32D ( IR ) cells , a myeloid progenitor cell stably overexpressing the insulin receptor , transfected with wild type human IRS 1 or the most common human variant of IRS 1 in which glycine 972 is replaced by arginine . ^^^ The changes occurred with no change in insulin receptor or IRS 1 tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Stimulation of protein synthesis , eukaryotic translation initiation factor 4E phosphorylation , and PHAS 1 phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3 kinase . ^^^ To study these pathways , we have used a myeloid progenitor cell line ( 32D ) which is dependent on interleukin 3 but insensitive to insulin because of the very low levels of insulin receptor ( IR ) and the complete lack of insulin receptor substrate ( IRS ) signaling proteins ( IRS 1 and IRS 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signalling and insulin actions in the muscles and livers of insulin resistant , insulin receptor substrate 1 deficient mice . ^^^ We and others recently generated mice with a targeted disruption of the insulin receptor substrate 1 ( IRS 1 ) gene and demonstrated that they exhibited growth retardation and had resistance to the glucose lowering effect of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Wortmannin is an inhibitor of phosphatidylinositol ( PI ) 3 ' kinase , a cellular kinase activated by docking to phosphotyrosyl residues of insulin receptor substrate 1 ( IRS 1 ) that can also phosphorylate serine residues on IRS 1 in vitro . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Neoplastic transformation induced by insulin receptor substrate 1 overexpression requires an interaction with both Grb 2 and Syp signaling molecules . ^^^ The insulin receptor substrate 1 ( IRS 1 ) is the major intracellular substrate of insulin and insulin like growth factor 1 ( IGF 1 ) receptor tyrosine kinase activity , and this protein has been found to be overexpressed in human hepatocellular carcinomas . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , treatment of CHO / HIRc cells with this N stearyl peptide led to a significant enhancement of the insulin induced association of phosphatidylinositol ( PI ) 3 kinase activity with insulin receptor substrate 1 and the activation of mitogen activated protein kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It has previously been shown that one important mechanism by which TNF alpha interferes with insulin signaling is through the serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , which can then function as an inhibitor of the tyrosine kinase activity of the insulin receptor ( IR ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
When the cells were incubated with both agents , okadaic acid inhibited insulin stimulated PI 3 kinase activity but did not block the association of the p 85 or p 110 subunits of PI 3 kinase with insulin receptor substrate 1 . ^^^ Insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 was only slightly reduced ( 15 30 % ) by okadaic acid . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , there was no decrease in the extent of insulin receptor substrate 1 , insulin receptor , or EGF receptor tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tumor necrosis factor alpha ( TNF alpha ) is a proposed mediator of insulin resistance in obese / diabetic animals through its effects on tyrosine phosphorylation of the insulin receptor and its substrate , insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A similar pattern was observed for insulin receptor autophosphorylation and Shc phosphorylation , whereas the duration of insulin receptor substrate 1 phosphorylation with low Kd analogues and with insulin was similar Thus the increased half life of the ligand receptor complex induces sustained activation of the insulin receptor tyrosine kinase and sustained phosphorylation of Shc , which may be the cause of the disproportionately high mitogenic potency seen for some insulin analogues . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased tyrosine phosphorylation levels of insulin receptors ( IRs ) and insulin receptor substrate 1 ( IRS 1 ) in response to insulin were not observed in fatty rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate 1 ( IRS 1 ) is expressed in 3T3 L 1 adipocytes and is involved in at least some insulin responses , notably mitogenesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of the major insulin receptor substrate IRS 1 was reduced by 50 + / 7 % , while its expression was decreased by 70 + / 4 % . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Using reverse transcription competitive PCR , we have measured the mRNAs encoding the two insulin receptor variants , the insulin receptor substrate 1 , the p85alpha subunit of phosphatidylinositol 3 kinase , Ras associated to diabetes ( Rad ) , the glucose transporter Glut 4 , glycogen synthase , 6 phosphofructo l kinase , lipoprotein lipase , and the hormone sensitive lipase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is the most well characterized cellular substrate for IGF 1 , containing at least 20 potential tyrosine phosphorylation sites . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Binding of IGF 1 to its pituitary cell surface receptor is followed by rapid activation of the intrinsic tyrosine kinase activity of the receptor beta subunit and phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of IRS 1 was compared among the transfected cell lines , since IRS 1 and Shc could competitively interact with insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 ( IRS 1 ) from hemizygous tissue was similar to that of wild type tissue . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Co immunoprecipitation with anti insulin receptor antibody , anti JAK 2 antibody , and anti IRS 1 antibody showed that JAK 2 interacts with the insulin receptor and IRS 1 to form stable complexes following stimulation by insulin . ^^^ In two animal models of insulin resistance the regulation of JAK 2 tyrosine phosphorylation after insulin infusion paralleled the phosphorylation of the insulin receptor and of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin responsive glucose transporter ( GLUT 4 ) translocation . ^^^ Interaction of the activated insulin receptor ( IR ) with its substrate , insulin receptor substrate 1 ( IRS 1 ) , via the phosphotyrosine binding domain of IRS 1 and the NPXY motif centered at phosphotyrosine 960 of the IR , is important for IRS 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Some evidence of involvement has been produced for insulin receptor substrate 1 , glycogen synthase , the glucagon receptor , a ras related protein ( Rad ) , histocompatibility antigens , PC 1 , and fatty acid binding protein , but the contributions of these genes to NIDDM is probably small . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The other peak was affected only slightly by G beta gamma , but was synergistically increased by G beta gamma and a tyrosine phosphorylated peptide which was synthesized accordingly to the amino acid sequence of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inactivity of a specific agonistic insulin receptor antibody ( B 10 ) confirms this and suggests that this action may be independent of signalling through IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After stimulation with 100 nM insulin , tyrosine phosphorylation of the insulin receptor was decreased by 31 % at 1 min ( P < 0 . 01 ) and by 42 % at 10 min ( P < 0 . 01 ) , and that of IRS 1 was decreased by 34 % ( P < 0 . 01 ) at 1 min and by 56 % ( P < 0 . 01 ) at 10 min in the LAR overexpressing cells compared with empty vector transfectants . ^^^ In contrast , overexpression of recombinant LAR cytoplasmic domain , detected as a 72 kDa protein in the cell cytosol , did not significantly affect the insulin stimulated tyrosine phosphorylation of the insulin receptor or IRS 1 ( 99 % and 93 % of control at 10 min , respectively ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No association between the Gly971Arg variant of the insulin receptor substrate 1 gene and NIDDM in the Taiwanese population . ^^^ OBJECTIVE To study the role of the Gly971Arg variant of the insulin receptor substrate 1 ( IRS 1 ) gene in the development of NIDDM in the Chinese population living in Taiwan . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular scanning of the insulin receptor substrate 1 ( IRS 1 ) gene in Japanese patients with NIDDM : identification of five novel polymorphisms . ^^^ Since the insulin receptor substrate 1 ( IRS 1 ) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol ( PI ) 3 kinase and promote GLUT 4 translocation , the IRS 1 gene is a potential candidate for development of non insulin dependent diabetes mellitus ( NIDDM ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced differentiation and modulation of neuronal thread protein expression in primitive neuroectodermal tumor cells is linked to phosphorylation of insulin receptor substrate 1 . ^^^ Analysis of the insulin mediated signal transduction pathway demonstrated that the lack of insulin responsiveness in PNET 1 cells was primarily caused by impaired insulin mediated tyrosyl phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) . ^^^ In contrast , the levels of IRS 1 protein were similar in PNET 1 and PNET 2 cells , and expression of the insulin receptor beta subunit ( Ir beta ) and insulin mediated tyrosyl phosphorylation of the Ir beta were greater in PNET 1 than PNET 2 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Concerning the insulin receptor cellular substrates , the anti ( 1294 1317 ) antibody inhibited Src homology / collagen and IRS 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
YMXM motifs and signaling by an insulin receptor substrate 1 molecule without tyrosine phosphorylation sites . ^^^ Tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) by the activated receptors for insulin , IGF 1 , and various cytokines creates binding sites for signaling proteins with Src homology 2 domains ( SH 2 proteins ) . ^^^
Interacting proteins: P06213 and P35568 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 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The wide variety of tyrosine phosphorylation motifs of insulin receptor substrate 1 ( IRS 1 ) , a substrate for the activated insulin receptor tyrosine kinase , may account for the multiple functions of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , we have examined the contribution of Tyr 1210 to insulin receptor specific responses as Tyr phosphorylation of IRS 1 , stimulation of glycogen synthesis , and dephosphorylation of focal adhesion kinase ( FAK ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 overexpression in human hepatocellular carcinoma cells prevents transforming growth factor beta 1 induced apoptosis . ^^^ Insulin like growth factors initiate tyrosyl phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) protein and activate multiple signaling pathways essential for liver growth . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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: P06213 and P35568 Pubmed SVM Score :0.0
Growth hormone stimulates tyrosine phosphorylation of JAK 2 and STAT 5 , but not insulin receptor substrate 1 or SHC proteins in liver and skeletal muscle of normal rats in vivo . ^^^ GH has been shown to stimulate tyrosine phosphorylation of JAK 2 , several STAT proteins , insulin receptor substrate 1 ( IRS 1 ) , and SHC proteins in cultured cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Bradykinin also enhanced insulin stimulated GLUT 4 translocation from the intracellular fraction to the cell membrane , and insulin induced phosphorylation of the insulin receptor beta subunit and insulin receptor substrate 1 ( IRS 1 ) without affecting the binding affinities or numbers of cell surface insulin receptors in dog adipocytes . ^^^ This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS 1 , followed by GLUT 4 translocation . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The abundance of insulin receptor substrate 1 ( IRS 1 ) and phosphatidylinositol ( PI ) 3 kinase mRNA and protein was significantly lower in rats fed a beef tallow diet versus a safflower oil diet . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The pleckstrin homology domain is the principal link between the insulin receptor and IRS 1 . ^^^ Interaction domains located in the NH 2 terminus of IRS 1 mediate its recognition by the insulin receptor . ^^^ In contrast , the IH 2 ( PTB ) and the SAIN regions were not required for these insulin actions ; however , the IH 2 ( PTB ) improved the coupling between IRS 1 and the insulin receptor . ^^^ Overexpression of the insulin receptor in 32DIR cells increased IRS 1 tyrosine phosphorylation and mediated insulin stimulated DNA synthesis . ^^^ Thus , the PH and PTB domains equally couple IRS 1 to high levels of insulin receptor normally expressed in most cells , whereas at low levels of insulin receptors the PTB domain is inefficient and the PH domain is essential for a productive interaction . . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 and its association with Grb 2 and the phosphatidylinositol 3 kinase . ^^^ In the present study , we demonstrate that gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , the major cytoplasmic substrate of the insulin receptor . ^^^ Taken together , our results suggest that IRS 1 may serve as a converging target in the signaling pathways stimulated by receptors that belong to different families , such as the gastrin / CCKB G protein coupled receptor and the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
GH induces phosphorylation of a number of cellular proteins , of which several have now been identified , such as mitogen activated protein kinase , insulin receptor substrate 1 , and members of the JAK kinase and STAT families of proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Other signalling molecules are involved in GH action through different pathways : GH is able to activate mitogen activated protein ( MAP ) kinases ; the hormone can utilize insulin receptor substrate 1 ( IRS 1 ) and induces the association of phosphatidylinositol 3 kinase with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Chem . 270 , 59 65 , 1995 ) demonstrates that in stimulated adipocytes , the internalized insulin receptor is not only more highly phosphorylated than the receptor remaining on the plasma membrane of the cell , but that IRS 1 binding and phosphorylation also occur in the endosomes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both insulin ( 100 nM ) and pervanadate ( 100 microM ) , a protein tyrosine phosphatase inhibitor , induced a marked increase in the phosphorylation at tyrosine residues of IR and insulin receptor substrate 1 ( IRS 1 ) and in 2 deoxyglucose uptake in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ang 2 did not enhance insulin induced insulin receptor substrate 1 ( IRS 1 ) phosporylation or phosphatidylinositol 3 ( PI 3 ) kinase activity , but did enhance insulin induced mitogen activated protein ( MAP ) kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Estradiol stimulates tyrosine phosphorylation of the insulin like growth factor 1 receptor and insulin receptor substrate 1 in the uterus . ^^^ Analysis of immunoprecipitates from uterine extracts revealed that E 2 enhanced tyrosine phosphorylation of the insulin like growth factor 1 receptor ( IGF 1R ) and insulin receptor substrate 1 ( IRS 1 ) by 6 hr . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Endotoxin induced alterations in insulin stimulated phosphorylation of insulin receptor , IRS 1 , and MAP kinase in skeletal muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We further demonstrate that IGF 1 is a potent activator of both insulin receptor substrate IRS 1 tyrosyl phosphorylation and association of IRS 1 with activated phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This induces the tyrosine phosphorylation of insulin receptor substrates 1 ( IRS 1 ) and a complex formation between IRS 1 and other proteins including GRB 2 , SH PTP 2 , Nck , and phosphoinositide ( PI ) 3 kinase consisting of a regulatory 85 kDa subunit and a catalytic 110 kDa subunit . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance and growth retardation in mice lacking insulin receptor substrate 1 and identification of insulin receptor substrate 2 . ^^^ To clarify the physiological roles of insulin receptor substrate 1 ( IRS 1 ) in vivo , we made mice with a targeted disruption of the IRS 1 gene locus . ^^^ Moreover , we identified tyrosine phosphorylation of a 190 kDa protein ( pp 190 ) as a novel substrate ( IRS 2 ) for insulin receptor kinase in livers of IRS 1 deficient mice which can bind both P 13 kinase and Ash / Grb2 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent data suggest involvement of the Janus tyrosine kinase 2 ( JAK 2 ) in human GH induced tyrosine phosphorylation of the GH receptor and the insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) , leading to activation of the phosphatidylinositol 3 kinase and the acute insulin like effects in primary rat adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activated insulin and insulin like growth factor 1 receptors transmit downstream signals via the insulin receptor substrate ( IRS 1 and IRS 2 ) and a series of proteins containing Src homology 2 ( SH 2 ) domains , including SH 2 containing protein tyrosine phosphatase 2 ( SHP 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is a protein expressed in 3T3 L 1 adipocytes that is involved in most , if not all of the biological responses to insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Following injection of AII into rats , we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) in the heart . ^^^ The latter occurs without any reduction in insulin receptor or IRS phosphorylation or in the interaction of the p 85 and p 110 subunits of PI 3 kinase with each other or with IRS 1 / IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is a major substrate of the insulin receptor tyrosine kinase and is an intermediate in insulin signaling . ^^^ Insulin receptor structural requirements for the formation of a ternary complex with IRS 1 and PI 3 kinase . ^^^ We examined the role of three insulin receptor tyrosine autophosphorylation domains in association of the receptor with IRS 1 . ^^^ Our data support the idea that tyrosine phosphorylation of the insulin receptor juxtamembrane domain is necessary for receptor association with IRS 1 . ^^^ In addition , our data show that the amount of PI 3 kinase directly associated with the insulin receptor C terminus is low when compared to the PI 3 kinase associating with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SH PTP 2 was shown to associate with a 115 kDa tyrosine phosphorylated protein ( pp 115 ) , as well as with insulin receptor substrate 1 , in insulin stimulated Chinese hamster ovary cells that overexpress human insulin receptors ( CHO IR cells ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we show that LTK utilizes insulin receptor substrate 1 ( IRS 1 ) and Shc as major two substrates and possesses two NPXY motifs for them separately , tyrosine 485 of one NPXY motif at the juxtamembrane domain for IRS 1 and tyrosine 862 of another NPXY motif at the carboxyl terminal domain for Shc . ^^^ Our results provide a useful insight in understanding the distinctive roles of Shc and IRS 1 in the signal transduction system of the insulin receptor family , and this anti apoptotic function of IRS 1 may explain the survival effects of insulin , IGF 1 , and interleukin 4 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mutant of insulin receptor substrate 1 incapable of activating phosphatidylinositol 3 kinase did not mediate insulin stimulated maturation of Xenopus laevis oocytes . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is rapidly phosphorylated on multiple tyrosine residues in response to insulin and binds several Src homology 2 domain containing proteins , thereby initiating downstream signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cloning of the chicken insulin receptor substrate 1 gene . ^^^ Upon ligand binding , these receptors become active kinases , undergoing autophosphorylation and phosphorylating cellular substrates , including insulin receptor substrate 1 ( IRS 1 ) . ^^^ In LMH cells , derived from a chicken hepatoma , two bands were tyrosine phosphorylated in an insulin dependent manner : IRS 1 ( approximately 180 kDa ) and the insulin receptor beta subunit ( approximately 95 kDa ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
For example , vanadate does not stimulate the tyrosine phosphorylation of the insulin receptor beta subunit nor the 170 kDa insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced egr 1 and c fos expression in 32D cells requires insulin receptor , Shc , and mitogen activated protein kinase , but not insulin receptor substrate 1 and phosphatidylinositol 3 kinase activation . ^^^ Insulin ' s effects are initiated by insulin binding to the insulin receptor , resulting in tyrosine phosphorylation of insulin receptor and intracellular substrates , such as insulin receptor substrate 1 ( IRS 1 ) , IRS 2 , or Shc . ^^^ In the present study , we examined the effects of insulin on immediate early gene egr 1 and c fos expression in 32D cells overexpressing the insulin receptor ( 32D / IR ) , IRS 1 ( 32D / IRS ) , or both ( 32D / IR+IRS ) and compared these effects with insulin induced tyrosine phosphorylation . ^^^ Insulin treatment ( 5 min at 37 degrees C ) markedly increased tyrosine phosphorylation of several proteins , including the insulin receptor , IRS 1 , and Shc , in 32D / IR+IRS cells as determined by immunoprecipitation and Western blot analysis with anti phosphotyrosine antibody . ^^^ These data suggest that insulin receptor and Shc phosphorylation is necessary for insulin induced egr 1 and c fos expression , but IRS 1 phosphorylation is not necessary or sufficient for the expression of these genes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Prior studies have demonstrated that a juxtamembrane tyrosine ( tyrosine 972 ) in the insulin receptor is required for the receptor to elicit various biological responses and to stimulate the tyrosine phosphorylation of two endogenous substrates , the insulin receptor substrate 1 and the adaptor protein called Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Transcriptional regulation of insulin receptor substrate 1 by protein kinase C . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is involved in insulin signal transduction distal to receptor occupation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we observed that > or = 1 nmol / L insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and activated IRS 1 dependent phosphatidylinositol 3 ' kinase ( PI 3 ' kinase ) and p 70 S6 kinase ( p70S6K ) but not MAP kinase ( extracellular signal regulated kinase 2 ) and p 90 S6 kinase ( p90RSK ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosyl phosphorylation of human insulin receptor substrate 1 occurred when HepG 2 cells were treated with the cultured medium , indicating that the h PPI gene product was functionally active in vitro . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These effects do not depend on decreased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 or the interaction of insulin receptor substrate 1 with phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) , beta 3 adrenergic receptor ( beta 3 AR ) and glycogen synthase ( GS ) genes are candidate genes for non insulin dependent diabetes mellitus ( NIDDM ) , insulin resistance , dyslipidaemia and obesity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Exposure of these cells to leptin , at concentrations comparable with those present in obese individuals , caused attenuation of several insulin induced activities , including tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) , association of the adapter molecule growth factor receptor bound protein 2 with IRS 1 , and down regulation of gluconeogenesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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: P06213 and P35568 Pubmed SVM Score :0.0
No significant results were obtained with glycogen synthase ( GSY ) , insulin receptor substrate 1 ( IRS 1 ) and apolipoprotein C 2 ( APOC 2 ) genes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tumor necrosis factor alpha induced insulin resistance in 3T3 L 1 adipocytes is accompanied by a loss of insulin receptor substrate 1 and GLUT 4 expression without a loss of insulin receptor mediated signal transduction . ^^^ Here we examine the effects of tumor necrosis factor on the protein components thought to be involved in insulin stimulated glucose transport in adipocytes , namely the insulin receptor , its major substrate IRS 1 , and the insulin responsive glucose transporter GLUT 4 . ^^^ Prolonged exposure ( 72 96 h ) of 3T3 L 1 adipocytes to TNF alpha causes a substantial reduction ( > 80 % ) in IRS 1 and GLUT 4 mRNA and protein as well as a lesser reduction ( > 50 % ) in the amount of the insulin receptor . ^^^ Both the insulin receptor and IRS 1 are tyrosine phosphorylated to the same extent in response to acute insulin stimulation following cellular TNF alpha exposure . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The injection of peroxovanadate also enhanced the tyrosine phosphorylation of many of the proteins known to function downstream of these receptors , including SHC , signal transducer and activator of transcription ( Stat ) 1alpha , beta , Stat 3 , Stat 5 , phospholipase C gamma , insulin receptor substrate 1 , GTPase activating protein , beta catenin , gamma catenin , p120cas , SHP 1 , and SHP 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) , and its structural relative IRS 2 , are both phosphorylated on tyrosine following treatment of cells with interleukin 4 ( IL 4 ) and insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , F 419 mutant protein is unable to phosphorylate insulin receptor substrate 1 ( IRS 1 ) or promote association of IRS 1 with phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Prolactin activates tyrosyl phosphorylation of insulin receptor substrate 1 and phosphatidylinositol 3 OH kinase . ^^^ Immunoblot analysis of immunoprecipitation indicates that p 85 corresponds to the 85 kDa regulatory subunit of phosphatidylinositol ( PI ) 3 ' kinase , p 95 to PRLR , and p 185 to insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol ( PI ) 3 kinase activity stimulated by insulin was also reduced by 36 % ( P < 0 . 001 ) , and expression of p 85 and p110b subunits of PI 3 kinase was normal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Roles of insulin receptor substrate 1 and Shc on insulin like growth factor 1 receptor signaling in early passages of cultured human fibroblasts . ^^^ Insulin receptor substrate 1 ( IRS 1 ) became tyrosine phosphorylated and bound growth factor receptor bound protein 2 ( GRB 2 ) quickly by IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Through its SH 2 domain , Nck recognizes a specific phosphotyrosine residue on RTKs or on protein substrates of RTKs like insulin receptor substrate 1 , the major substrate of the insulin receptor , and through its SH 3 domains it interacts with poorly characterized effector molecules . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS ( insulin receptor substrate ) 1 and IRS 2 were also phosphorylated constitutively in both ovarian cancer cell lines examined , but only the phosphorylation of IRS 1 was augmented in response to IL 4 or IL 13 . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
In order to determine whether the effects of TNF alpha might involve alterations in the expression of specific protein tyrosine phosphatases ( PTPases ) that have been implicated in the regulation of growth factor receptor signalling , KRC 7 rat hepatoma cells were treated with TNF alpha , and changes in overall tissue PTPase activity and the abundance of three major hepatic PTPases ( LAR , PTP1B , and SH PTP 2 ) were measured in addition to effects of TNF alpha on ligand stimulated autophosphorylation of insulin and epidermal growth factor ( EGF ) receptors and insulin stimulated insulin receptor substrate 1 ( IRS 1 ) phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , insulin stimulated tyrosine phosphorylation of the endogenous insulin receptor substrates IRS 1 and Shc were decreased to 57 % and 73 % of control , respectively , and IRS 1 associated phosphatidylinositol 3 ' kinase activity was reduced to 47 % of control of the cells overexpressing LAR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is one of the major substrates of insulin receptor tyrosine kinase and mediates multiple insulin signals downstream . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 phosphorylation and phosphatidylinositol 3 kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation . ^^^ We examined the effect of physiological hyperinsulinemia on insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation and phosphatidylinositol ( PI ) 3 kinase activity in skeletal muscle from six lean to moderately obese NIDDM patients and six healthy subjects . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Shc and insulin receptor substrate 1 ( IRS 1 ) are cytoplasmic substrates of tyrosine kinase receptors that engage , localize , and activate downstream SH 2 enzymes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Differential signaling by insulin receptor substrate 1 ( IRS 1 ) and IRS 2 in IRS 1 deficient cells . ^^^ Mice made insulin receptor substrate 1 ( IRS 1 ) deficient by targeted gene knockout exhibit growth retardation and abnormal glucose metabolism due to resistance to the actions of insulin like growth factor 1 ( IGF 1 ) and insulin ( E . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mice double heterozygous for null alleles in the insulin receptor and insulin receptor substrate 1 genes exhibit the expected approximately 50 % reduction in expression of these two proteins , but a synergism at a level of insulin resistance with 5 to 50 fold elevated plasma insulin levels and comparable levels of beta cell hyperplasia . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This interaction differs from that occurring between other PID / PTB domain containing proteins , such as Shc and insulin receptor substrate 1 , and activated growth factor receptors as follows : ( 1 ) the Fe 65 APP interaction is phosphorylation independent ; ( 2 ) the region of the APP intracellular domain involved in the binding is larger than that of the growth factor receptor necessary for the formation of the complex with Shc ; and ( 3 ) despite a significant similarity the carboxyl terminal regions of PID / PTB of Fe 65 and of Shc are not functionally interchangeable in terms of binding cognate ligands . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The objective of this study was to investigate the mechanism of dexamethasone action by determining its effects on the expression of the p85alpha and p85beta regulatory subunit isoforms of PI 3 kinase , their coupling with the p 110 catalytic subunit , and their association with insulin receptor substrate 1 ( IRS 1 ) in response to IGF 1 stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , the IGF IR and its two substrates , insulin receptor substrate 1 and SHC , were contained within the E cadherin complexes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found that two proteins associated with the insulin signal cascade , the beta subunit of the insulin receptor and IRS 1 , increased in tyrosyl phosphorylation in the presence of selenium . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Development of non insulin dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate 1 and beta cell glucokinase genes . ^^^ Homozygous mice with insulin receptor substrate 1 ( IRS 1 ) gene knockout showed normal glucose tolerance associated with insulin resistance and compensatory hyperinsulinemia . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Influence of ethanol on insulin receptor substrate 1 mediated signal transduction during rat liver regeneration . ^^^ Insulin is a potent hepatotrophic factor , and tyrosyl phosphorylation ( TP ) of the intracellular insulin receptor substrate 1 ( IRS 1 ) protein plays a crucial role in hepatocyte growth . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We isolated a cDNA that encodes a 50 kDa regulatory subunit of PI 3 kinase with an expression cloning method using 32P labeled insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Glucose induced insulin secretion is impaired and insulin induced phosphorylation of the insulin receptor and insulin receptor substrate 1 are increased in protein deficient rats . ^^^ Immunoblotting and immunoprecipitation were used to study the phosphorylation of the insulin receptor and the insulin receptor substrate 1 as well as the insulin receptor substrate 1 p 85 subunit of phosphatidylinositol 3 kinase association in response to insulin . ^^^ No differences were detected in the total amount of protein corresponding to the insulin receptor or insulin receptor substrate 1 between muscle from rats fed the two diets . ^^^ Therefore , we conclude that a decreased glucose induced insulin secretion in pancreatic islets from protein malnourished rats is responsible , at least in part , for an increased phosphorylation of the insulin receptor , insulin receptor substrate 1 and its association with phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Changes in the NMR derived motional parameters of the insulin receptor substrate 1 phosphotyrosine binding domain upon binding to an interleukin 4 receptor phosphopeptide . ^^^ Recently , we determined the solution structure of the phosphotyrosine binding ( PTB ) domain of the insulin receptor substrate ( IRS 1 ) complexed to a tyrosine phosphorylated peptide derived from the interleukin 4 ( IL 4 ) receptor [ Zhou et al . , ( 1996 ) Nat . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The overall architecture of pp 60 is thus the same as that of insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) , and furthermore both the pleckstrin homology and phosphotyrosine binding domains are highly homologous ( about 50 % identical amino acids ) to these domains in both IRS 1 and IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here , using two hybrid assays and in vitro assays of protein interaction , we show that the epsilon isoform of 14 3 3 interacts with the insulin like growth factor 1 receptor ( IGFIR ) and with insulin receptor substrate 1 ( IRS 1 ) , but not with the insulin receptor ( IR ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
CSF 1 stimulated the tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and Shc in cells expressing the CSF1R / IR chimera . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This chapter reviews our current knowledge of the phosphorylation signaling pathways activated by insulin and presents evidence that substrates other than insulin receptor substrate 1 are involved in insulin ' s regulation of immediate early gene expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Angiotensin 2 stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein tyrosine phosphatase 1D in vascular smooth muscle cells . ^^^ In rat aortic vascular smooth muscle cells , IGF 1 ( 20 ng / ml ) induced a sustained ( > 30 min ) increase in the tyrosine phosphorylation of both Src homology 2 domain docking insulin receptor substrate 1 ( IRS 1 ) and Src homology 2 binding tyrosine phosphatase 1D ( PTP 1D ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , we also demonstrate that IL 13 stimulates the tyrosine phosphorylation of the adaptor molecule insulin receptor substrate 1 , which may facilitate receptor coupling to PtdIns 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate ( IRS ) 2 is dephosphorylated more rapidly than IRS 1 via its association with phosphatidylinositol 3 kinase in skeletal muscle cells . ^^^ Insulin receptor substrate ( IRS ) 2 is structurally and functionally similar to IRS 1 . ^^^ Taken together , these observations suggest that IRS 2 plays a unique role in mediating the signals from the insulin receptor to downstream molecules and that this effect is more transient than that of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Previously we have demonstrated that IGFs and insulin stimulate Y 79 cell proliferation through the involvement of type 1 IGF receptor and Insulin Receptor Substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
M 16209 ( 100 microM ) did not interfere with ( 125 ) 1 insulin binding or with tyrosine phosphorylation of the insulin receptor beta subunit and IRS 1 . ^^^ Insulin binding to its receptor , autophosphorylation of the insulin receptor beta subunit , and tyrosine phosphorylation of IRS 1 were unaffected by M 16209 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , spontaneously hypertensive rats have decreased expression of the insulin receptor gene in the liver and decreased receptor autophosphorylation and phosphorylation of an endogenous substrate ( IRS 1 ) in liver and muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Relationship between insulin sensitivity and insulin receptor substrate 1 mutations in non diabetic relatives of NIDDM families . ^^^ Insulin receptor substrate 1 ( IRS 1 ) occupies a key position in the insulin signalling pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) is one of the major substrates of insulin receptor tyrosine kinase and mediates various insulin signals downstream . ^^^ G971R is located near src homology 2 protein binding sites , and P170R and M209T are located in the phosphotyrosine binding domain of IRS 1 . 32D IR cells , stably overexpressing human insulin receptor , were transfected with wild type human IRS 1 cDNA ( WT ) or three mutant IRS 1 cDNAs and analyzed . ^^^ After insulin stimulation , cells expressing P170R and M209T showed significant decreases in IRS 1 phosphorylation ( 37 and 42 % , respectively ; both P < 0 . 05 ) and in IRS 1 binding to the insulin receptor ( 48 and 53 % , respectively ; P < 0 . 01 ) compared with WT . ^^^ G971R showed no changes in IRS 1 phosphorylation and in IRS 1 binding to the insulin receptor compared with WT . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To elucidate genetic determinants of insulin resistance , we investigated insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) genes , in vitro IR function and in vivo insulin sensitivity in a family with Type A syndrome . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Pretreatment for about 3 h with dibutyryl cAMP or cAMP generating agents clearly increased insulin dependent tyrosine phosphorylation of the 195 kDa protein , but not IRS 1 , IRS 2 or the insulin receptor beta subunit . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These results reveal a novel mechanism regulating the interaction of the insulin receptor and IRS 2 that may distinguish the signal of IRS 2 from IRS 1 . . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The active insulin receptor phosphorylates tyrosine residues of intracellular proteins such as the insulin receptor substrate 1 ( IRS 1 ) which acts as docking sites for molecules containing Src homology 2 ( SH 2 ) domains . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 gene polymorphism and cardiovascular risk in non insulin dependent diabetes mellitus and patients undergoing coronary angiography . ^^^ To investigate the relationship between a coding polymorphism in the insulin receptor substrate 1 gene and the presence of cardiovascular risk factors , 209 patients with NIDDM and 452 subjects investigated for coronary artery disease ( CAD ) were studied . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) and phosphatidylinositol ( PI ) 3 kinase protein levels decreased in the liver but not muscle of GH treated rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It is now necessary to study other steps of the insulin signal transduction pathway , such as insulin receptor substrate 1 phosphorylation . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates the tyrosine kinase activity of its receptor , resulting in the phosphorylation of its cytosolic substrate , insulin receptor substrate 1 ( IRS 1 ) . ^^^ In the present study we investigated the levels and phosphorylation state of IRS 1 after insulin stimulation in the rat aorta in vivo , and the modulation of this protein after 72 h of fasting , using immunoprecipitation and immunoblotting with anti insulin receptor , anti IRS 1 and antiphosphotyrosine antibodies . ^^^ After insulin stimulation , rats fasted for 72 h showed an increase in insulin receptor ( 100 + / 45 % , P < 0 . 05 ) and IRS 1 phosphorylation ( 68 + / 24 % , P < 0 . 05 ) in aorta , compared to fed rats . ^^^ There was no change in insulin receptor of IRS 1 protein levels in fasted rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Similarly , insulin stimulated phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was decreased 25 % by GH , but the abundance of IRS 1 was not affected . ^^^ Growth hormone induced insulin resistance : role of the insulin receptor , IRS 1 , GLUT 1 , and GLUT 4 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin also stimulated insulin receptor substrate 1 tyrosine phosphorylation and subsequently activated phosphatidylinositol 3 kinase . ^^^ Transformed brown adipocyte cell line ( by permanent simian virus 40 large T antigen and pMEXneo H ras ( lys 12 ) cotransfection ) developed insulin resistance upstream from Ras , showing an impairment in the insulin receptor autophosphorylation , and in insulin receptor substrate 1 tyrosine phosphorylation and its association with phosphatidylinositol 3 kinase upon treatment with 1 nM insulin , although insulin receptor number and affinity ( Kd ) remained unaltered . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We demonstrate that , in addition to activation of the Jak 1 and Jak 3 kinases , IL 7 stimulation of human thymocytes results in the rapid tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and IRS 2 proteins . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
The majority of proteins in this latter band were immunoprecipitated by antibodies against insulin receptor substrate ( IRS ) 2 and not by antibodies against IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
When cells were preincubated for 5 15 min with PDGF , PI 3 kinase activity associated to insulin receptor substrate 1 ( IRS 1 ) in response to insulin was decreased , due to reduced association of the PI 3 kinase p 85 subunit with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The expression of insulin receptor substrate 1 ( IRS 1 ) mRNA was demonstrated in rat luteal cells by Northern blot analysis , in situ hybridization as well as by reverse transcriptase polymerase chain reaction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of insulin receptor substrate 1 and activation of the PI 3 kinase pathway by glycine extended gastrin precursors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
By utilizing the insulin receptor substrate ( IRS ) proteins ( IRS 1 and IRS 2 ) , the insulin signal can be amplified or attenuated independently of insulin binding and tyrosine kinase activity , providing an extensible mechanism for signal transmission in multiple cellular backgrounds . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of the insulin receptor beta subunit and the insulin receptor substrate 1 ( IRS 1 ) was stimulated identically in cardiomyocytes from both lean and obese rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , the PH and PTB domains are highly homologous ( at least 40 % identical ) to those found in insulin receptor substrates 1 , 2 , and 3 ( IRS 1 , IRS 2 , and IRS 3 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To address whether Ras can be activated by insulin in the PC 12 cell line , proteins interacting with insulin receptor and IRS 1 molecules and their tyrosine phosphorylation were analyzed by immunoblotting following immunoprecipitation with antibodies . ^^^ Tyrosine phosphorylation of the insulin receptor and IRS 1 was increased by insulin . ^^^ Grb 2 and Ras GAP appeared in the immunoprecipitates by anti insulin receptor and anti IRS 1 from insulin treated cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The ability of insulin to stimulate protein synthesis and cellular growth is mediated through the insulin receptor ( IR ) , which phosphorylates Tyr residues in the insulin receptor substrate signaling proteins ( IRS 1 and IRS 2 ) , Gab 1 , and Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action . ^^^ The phosphorylation of insulin receptor substrate 1 ( IRS 1 ) on tyrosine residues by the insulin receptor ( IR ) tyrosine kinase is involved in most of the biological responses of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
WT , the hIRDeltaNPEY mutant demonstrated the following : ( a ) normal insulin mediated receptor tyrosine phosphorylation , but approximately 50 % reduction in phosphorylation of p 185 ( insulin receptor substrate 1 ) and binding of the p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) , ( b ) an enhanced stimulation of PI 3 kinase enzymatic activity , ( c ) a complete inability to phosphorylate Shc , ( d ) minimal impairment of insulin sensitivity for glycogen synthesis , and ( e ) an augmented response to insulin stimulated DNA synthesis via a high capacity , low sensitivity pathway . ^^^ These results demonstrate the following : 1 ) the NPEY 972 sequence is important but not absolutely essential for coupling of hIR kinase to insulin receptor substrate 1 and p 85 or for mediating insulin ' s metabolic and mitogenic effects , 2 ) the NPEY 972 sequence is necessary for Shc phosphorylation , and 3 ) the absence of Shc phosphorylation releases the constraints on maximal insulin stimulated mitogenic response , thus indicating that alternate signaling pathway ( s ) exist for this insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Co operation of simian virus 40 T antigen and insulin receptor substrate 1 in protection from apoptosis induced by interleukin 3 withdrawal . 32D cells are interleukin 3 ( IL 3 ) dependent murine hemopoietic cells , that undergo apoptosis after IL 3 withdrawal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Changes in tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 ( IRS 1 ) and association of p 85 of phosphatidylinositol 3 kinase with IRS 1 after feeding in rat liver in vivo . ^^^ The binding of insulin to its receptor rapidly induces intrinsic insulin receptor tyrosine kinase activity , resulting in tyrosine phosphorylation of various cytosolic substrates , such as insulin receptor substrate 1 ( IRS 1 ) which , in turn , associates with a p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) followed by activation of this enzyme . ^^^ Because tyrosine phosphorylation of the insulin receptor beta subunit and IRS 1 and the association of the p 85 subunit of PI 3 kinase with IRS 1 in liver were closely correlated with the changes in the plasma concentration of insulin , we concluded that endogenous insulin secreted in response to eating caused these insulin dependent intracellular changes in the liver . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , immunoprecipitation of insulin receptor substrate 1 ( IRS 1 ) showed that the p 85 regulatory subunit of phosphatidylinositol 3 kinase did not associate with IRS 1 upon contraction but with a marked stimulated association in response to insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These were compared with fibroblasts from normoinsulinaemic normoglycaemic controls and from subjects with known genetic defects in the insulin receptor or IRS 1 . ^^^ Surprisingly , subjects with insulin receptor or IRS 1 mutations had a profound reduction in PC 1 activity ( p < or = 0 . 005 ) , protein ( p < or = 0 . 05 ) and mRNA levels ( P < or = 0 . 005 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Biological effects of human insulin receptor substrate 1 overexpression in hepatocytes . ^^^ The human insulin receptor substrate 1 ( hIRS 1 ) is a key intracellular protein involved in various cytokine signaling pathways associated with cell growth . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Janus kinase dependent activation of insulin receptor substrate 1 in response to interleukin 4 , oncostatin M , and the interferons . ^^^ In addition to a role in response to insulin and insulin like growth factors , insulin receptor substrate 1 ( IRS 1 ) is phosphorylated in response to IL 4 , the interferons ( IFNs ) and oncostatin M ( OSM ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , the stimulatory action of Gbetagamma was markedly enhanced by the simultaneous addition of a phosphotyrosyl peptide synthesized according to the amino acid sequence of the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To evaluate the function of 2 post receptor signaling molecules , insulin receptor substrate 1 ( IRS 1 ) ( a major substrate of the IGF IR ) and SHC ( a common substrate of tyrosine kinase receptors ) , we developed several MCF 7 derived cell clones in which the synthesis of either IRS 1 or SHC was blocked by antisense RNA . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
HMG 1 ( Y ) phosphorylation status as a nuclear target regulated through insulin receptor substrate 1 and the I4R motif of the interleukin 4 receptor . ^^^ Moreover , IL 4 is unable to induce HMG 1 ( Y ) phosphorylation in insulin receptor substrate 1 deficient cells , and the inhibitor wortmannin completely blocks IL 4 regulation of HMG 1 ( Y ) phosphorylation status but not activation of an IL 4 Stat protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vivo insulin stimulated phosphoinositide 3 kinase activity , pivotal in translocation of GLUT 4 , was decreased in burns when assessed by its insulin receptor substrate 1 ( IRS 1 ) associated activity . ^^^ Insulin induced tyrosine kinase activity of insulin receptor ( IR ) and tyrosine phosphorylation of IRS 1 were also attenuated . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we show that TZDs have powerful effects on the ability of TNF alpha to alter the most proximal steps of insulin signaling , including tyrosine phosphorylation of the insulin receptor and its major substrate , IRS 1 , and activation of PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS AND RESULTS : Rat balloon injured carotid artery was analyzed for phosphotyrosine content of PDGF alpha and beta receptors , epidermal growth factor ( EGF ) receptors , and insulin receptor substrate 1 ( IRS 1 ) by immunoprecipitation and anti phosphotyrosine Western blot . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Role of insulin receptor substrate 1 and pp 60 in the regulation of insulin induced glucose transport and GLUT 4 translocation in primary adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To identify molecular defects responsible for this disease , we tested the implication of 14 candidate genes coding for proteins involved either in insulin action , i . e . insulin receptor , insulin receptor substrate 1 , insulin like growth factor 1 receptor , diabetes associated ras like protein ( Rad ) , and glycogen synthase , or in lipid metabolism , i . e . lipoprotein lipase ; apolipoproteins CII , AII , and CIII ; hepatic lipase ; hormone sensitive lipase ; the beta 3 adrenergic receptor ; leptin ; and fatty acid binding protein 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein kinase C modulation of insulin receptor substrate 1 tyrosine phosphorylation requires serine 612 . ^^^ Activation of the endogenous protein kinase Cs in human kidney fibroblast ( 293 ) cells was found in the present study to inhibit the subsequent ability of insulin to stimulate the tyrosine phosphorylation of an expressed insulin receptor substrate 1 . ^^^ To test whether serine phosphorylation of the insulin receptor substrate 1 was contributing to this process , serine 612 of this molecule was changed to an alanine . ^^^ Activation of protein kinase C was found to stimulate by 10 fold the ability of a cytosolic kinase to phosphorylate this synthetic peptide as well as the intact insulin receptor substrate 1 . ^^^ These results indicate that activation of protein kinase C stimulates a kinase which can phosphorylate insulin receptor substrate 1 at serine 612 , resulting in an inhibition of insulin signaling in the cell , posing a potential mechanism for insulin resistance in some models of obesity . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Two early events downstream of insulin receptor autophosphorylation that are necessary for activation of glucose transport in adipocytes appear to be : ( 1 ) The tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) which ( 2 ) recruits and activates phosphatidylinositol 3 ' kinase ( PI3 ' K ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Heterologous pleckstrin homology domains do not couple IRS 1 to the insulin receptor . ^^^ Based on the hypothesis that PH domains may have a common function such as membrane targeting we tested the ability of PH domains from other signaling molecules to link IRS 1 to the insulin receptor . ^^^ In contrast , heterologous PH domains from the beta adrenergic receptor kinase , phospholipase Cgamma , or spectrin failed to mediate tyrosine phosphorylation of chimeric IRS 1 proteins , even in cells expressing high levels of insulin receptor . ^^^ Moreover , IRS 1 proteins containing heterologous PH domains did not bind phosphorylated NPEY motifs derived from the insulin receptor , suggesting that the presence of these structures interfered with the function of the adjacent PTB binding domain . ^^^ Thus , tyrosine phosphorylation of IRS 1 by the insulin receptor specifically requires a PH domain derived from IRS proteins . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin like effects of vanadate are independent of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Concomitant insulin stimulation ( three to six fold [ P < 0 . 05 ] ) of thigh glucose clearance , muscle insulin receptor tyrosine kinase ( IRTK ) , insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , and IRS 1 associated phosphatidylinositol 3 kinase ( PI 3 kinase ) was observed in the rested leg . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrates 1 and 2 ( IRS 1 and 2 ) are important substrates of the insulin receptor tyrosine kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Elevated serine / threonine phosphorylation of IRS 1 and IRS 2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin induced tyrosine phosphorylation . ^^^ Tumor necrosis factor alpha ( TNFalpha ) or chronic hyperinsulinemia that induce insulin resistance trigger increased Ser / Thr phosphorylation of the insulin receptor ( IR ) and of its major insulin receptor substrates , IRS 1 and IRS 2 . ^^^ To unravel the molecular basis for this uncoupling in insulin signaling , we undertook to study the interaction of Ser / Thr phosphorylated IRS 1 and IRS 2 with the insulin receptor . ^^^ Such impaired interactions abolish the ability of IRS 1 and IRS 2 to undergo insulin induced Tyr phosphorylation and further propagate the insulin receptor signal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated tyrosine phosphorylation of the insulin receptor beta subunit and insulin receptor substrate 1 ( IRS 1 ) in intact skeletal muscle of SHROB was reduced by 36 and 23 % , respectively , compared with SHR , due primarily to 32 and 60 % decreases in insulin receptor and IRS 1 protein expression , respectively . ^^^ In the liver of SHROB , the effect of insulin on tyrosine phosphorylation of IRS 1 was not changed , but insulin receptor phosphorylation was decreased by 41 % , compared with SHR , due to a 30 % reduction in insulin receptor levels . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 gene variants in lipoatrophic diabetes mellitus and non insulin dependent diabetes mellitus : a study of South African black and white subjects . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates a significant increase in PI 3 K activity associated with insulin receptor substrate 1 as well as an increase in insulin receptor substrate 1 / PI 3 K mass in LDM . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IGFBP 7 blocks insulin binding to the insulin receptor and thereby inhibiting the earliest steps in insulin action , such as autophosphorylation of the insulin receptor beta subunit and phosphorylation of IRS 1 , indicating that IGFBP 7 is a functional insulin binding protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
WF cells demonstrated a greater degree of ligand stimulated insulin receptor substrate 1 phosphorylation when compared with W cells , suggesting that expression of the EWS / FLI 1 fusion protein alters the IGF IR signaling pathway . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We stimulated C2C12 myotubes with insulin ( 100 nmol / l , 5 min ) or leptin ( 0 . 62 nmol / l , 10 min ) and determined PI 3 kinase activity in immunoprecipitates with specific non crossreacting antibodies against insulin receptor substrate ( IRS 1 / IRS 2 ) and against janus kinase ( JAK 1 and JAK 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In accord with this observation , tyrosine phosphorylated activation of insulin receptor substrate 1 , detected by immunoprecipitation and Western immunoblot analysis in mammary tumors of WC rats from our previous study , was 3 5 times greater than in non restricted controls ( P < 0 . 01 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Modulation of insulin receptor substrate 1 tyrosine phosphorylation and function by mitogen activated protein kinase . ^^^ Increased serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) has been observed in several systems to correlate with a decreased ability of the insulin receptor to tyrosine phosphorylate this endogenous substrate and to inhibit its subsequent association with phosphatidylinositol 3 kinase . ^^^ First , recombinantly produced kinase was shown to phosphorylate intact IRS 1 in a way that decreased the ability of isolated insulin receptor to phosphorylate the tyrosines recognized by the SH 2 domains of the phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increasing HLA : IR also enhanced phosphorylation of insulin receptor substrate 1 and the activation of phosphoinositide 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of variant forms of insulin receptor substrate 1 identified in patients with noninsulin dependent diabetes mellitus . ^^^ Several polymorphisms have been identified in the amino acid sequence of human insulin receptor substrate 1 ( IRS 1 ) . ^^^ The mutations did not alter the level of expression or the extent of insulin receptor mediated tyrosine phosphorylation of recombinant IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Differential regulation of insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) and phosphatidylinositol 3 kinase isoforms in liver and muscle of the obese diabetic ( ob / ob ) mouse . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To investigate potential interactions between angiotensin 2 ( AII ) and the insulin signaling system in the vasculature , insulin and AII regulation of insulin receptor substrate 1 ( IRS 1 ) phosphorylation and phosphatidylinositol ( PI ) 3 kinase activation were examined in rat aortic smooth muscle cells . ^^^ While AII did not impair insulin stimulated tyrosine phosphorylation of the insulin receptor ( IR ) beta subunit , it decreased insulin stimulated tyrosine phosphorylation of IRS 1 by 50 % . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In 293 cells association of p55PIK with insulin receptor substrate 1 and with IGF IR was dependent on PI 3 kinase , since it was increased by wortmannin , an inhibitor of PI 3 kinase . ^^^ Importantly , this dominant negative mutant was more efficient than wild type p55PIK in associating to IGF IR and insulin receptor substrate 1 in 293 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin binding to its receptor activates a tyrosine kinase that initiates a cascade of signaling events , the initial step being the tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To elucidate the mechanism of obesity related insulin resistance , we investigated the impaired steps in the processes of phosphatidylinositol ( PI ) 3 kinase activation through binding with insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) in liver and muscle of Zucker fatty rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Long term increases in PI 3 kinase activity associated with insulin receptor substrate 1 ( IRS 1 ) increased GLUT 1 and GLUT 4 concentrations in plasma membranes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No difference in mRNA expression between omental and subcutaneous adipose tissue was observed for hormone sensitive lipase , lipoprotein lipase , 6 phosphofructo 1 kinase , insulin receptor substrate 1 , p85alpha regulatory subunit of phosphatidylinositol 3 kinase , and Rad . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Bisphosphorylated TAMs ( tyrosine based activation motifs ) were derived from biologically relevant sites in platelet derived growth factor , T cell , B cell , and high affinity IgE receptors and the receptor substrates IRS 1 ( insulin receptor substrate 1 ) and SHPS 1 / SIRP . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A significant amount of insulin receptor substrate 1 ( IRS 1 ) was immunodetected in the immunoprecipitate with anti 14 3 3beta antibody at the basal condition . 100 nM insulin increased the amount of IRS 1 in the immunoprecipitate 2 . 5 fold . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates tyrosine phosphorylation of 175 195 kDa proteins including insulin receptor substrate 1 ( IRS 1 ) in various tissues and cell types . ^^^ In intact rat livers , starvation increased the insulin dependent tyrosine phosphorylation of the insulin receptor and IRS 1 as has been described by others . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , insulin stimulated tyrosine phosphorylation of insulin receptor ( IR ) substrate 1 ( IRS 1 ) was decreased more than 90 % compared with control values , while a twofold increase in basal IRS 1 phosphorylation status was observed in diabetic GK rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
At 37 C , insulin stimulated insulin receptor substrate 1 ( IRS 1 ) phosphorylation is inhibited by 50 % in CHO IRC860S , whereas Shc phosphorylation remains unaffected . ^^^ The inhibition of IRS 1 phosphorylation is still present when experiments are conducted at 4 C , a temperature at which insulin receptor internalization is prevented , suggesting that the defect in IRS 1 phosphorylation is not due to the reduced internalization of the receptor . ^^^ Eventually , the events observed are specific for Cys 860 , as individual substitution of the two more proximal Cys residues ( 795 and 872 ) to Ser is not accompanied by any change in either insulin induced insulin receptor internalization or IRS 1 phosphorylation . ^^^ Thus , the present analysis of CHO IRC860S 1 ) reveals that insulin receptor surface redistribution is not solely dependent on receptor autophosphorylation , 2 ) emphasizes that IRS 1 phosphorylation is not dependent on receptor internalization and can be triggered from microvilli , and 3 ) stresses divergent aspects between two of the major signaling pathways of the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was markedly increased in response to PIG P in rat cardiomyocytes without any effect on the tyrosine phosphorylation of the insulin receptor beta subunit . ^^^ Increased tyrosine phosphorylation of IRS 1 and enhanced PI 3 kinase activity in response to PIG P independent of the insulin receptor was also observed in isolated adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Overexpression of insulin receptor substrate 1 emerges early in hepatocarcinogenesis and elicits preneoplastic hepatic glycogenosis . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a multisite docking protein occupying a central position in signaling cascades stimulated by a number of growth factors including insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A preliminary experiment provided evidence suggesting that muscle insulin signaling , as reflected in binding of phosphatidylinositol 3 kinase to the insulin receptor substrate 1 , was enhanced in the DHEA treated and wheel running groups as compared to controls . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , dexamethasone down regulated insulin receptor substrate 1 protein content by 42 % and insulin induced tyrosine phosphorylation of insulin receptor substrate 1 by 28 % . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) and Shc protein have the same binding site at the insulin receptor and compete in their association with the phosphorylated receptor . ^^^ The present study demonstrates that a decrease in the level of muscle insulin receptor phosphorylation induced by chronic growth hormone ( GH ) treatment or acute epinephrine infusion is accompanied by a reduction in the level of IRS 1 phosphorylation and in the association with phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin like growth factor 1 receptor internalization regulates signaling via the Shc / mitogen activated protein kinase pathway , but not the insulin receptor substrate 1 pathway . ^^^ Insulin like growth factor 1 ( IGF 1 ) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins , including insulin receptor substrate 1 ( IRS 1 ) and the Shc proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A rho associated protein kinase , ROKalpha , binds insulin receptor substrate 1 and modulates insulin signaling . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is phosphorylated on multiple tyrosine residues by ligand activated insulin receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The negative effect of RPTPalpha on insulin activation of the prolactin promoter is not due to reduced phosphorylation or kinase activity of the insulin receptor or to reduced phosphorylation of insulin receptor substrate 1 or Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After insulin binding , insulin receptors ( IR ) phosphorylate the insulin receptor substrate 1 ( IRS 1 ) on specific motifs and thereby initiate insulin action . ^^^ Nutritional state regulates insulin receptor and IRS 1 phosphorylation and expression in chicken . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Genetic and biochemical studies indicated that this impairment was not secondary to a defect in the structure , expression , or activation of the insulin receptor , IRS 1 , or p85alpha . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Intracellular localization of phosphatidylinositide 3 kinase and insulin receptor substrate 1 in adipocytes : potential involvement of a membrane skeleton . ^^^ Phosphatidylinositide ( PI ) 3 kinase binds to tyrosyl phosphorylated insulin receptor substrate 1 ( IRS 1 ) in insulin treated adipocytes , and this step plays a central role in the regulated movement of the glucose transporter , GLUT 4 , from intracellular vesicles to the cell surface . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Comparison of 32P peptide maps of IRS 1 phosphorylated in vitro by the insulin receptor vs . ^^^ Taking our data together , we conclude that : 1 ) insulin and IGF 1 lead to phosphorylation and activation of JAK 1 and JAK 2 in intact cells ; 2 ) phosphorylation of IRS 1 by JAK 1 seems to occur on sites different from those phosphorylated by the insulin receptor ; 3 ) JAK 1 interacts directly with phosphorylated insulin and IGF 1 receptors ; and 4 ) the JH 7 JH6 and JH 1 domains of JAK 1 are responsible for the interaction with insulin and IGF 1 receptors . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates the tyrosine kinase activity of its receptor , resulting in the phosphorylation of its cytosolic substrate , insulin receptor substrate 1 ( IRS 1 ) . ^^^ After insulin stimulation the levels of insulin receptor and IRS 1 tyrosine phosphorylation were reduced to 79 + / 5 % ( P < 0 . 005 ) and 58 + / 6 % ( P < 0 . 0001 ) , respectively , of the control ( C ) levels , in the remnant kidney . ^^^ These data demonstrate that after unilateral nephrectomy there is a decrease in insulin induced insulin receptor and IRS 1 tyrosine phosphorylation levels in kidney but not in liver and muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulation results in a considerable spectrum of cellular responses , only part of which have been firmly correlated with the activation of established insulin receptor ( IR ) targets such as IRS 1 , IRS 2 , and Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These observations indicate that the anti apoptotic effects of the insulin receptor cytoplasmic domain can be mediated by signaling pathways distinct from those requiring IRS 1 and Shc . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent studies have started to assess the effects of oestrogen on the expression of components of the IGF signal transduction pathway , and have shown that the expression of insulin receptor substrate 1 , the principal substrate for the tyrosine kinase of the type 1 IGF receptor , is regulated by oestradiol . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Also , insulin stimulated phosphatidylinositol ( PI ) 3 kinase activity was normal , suggesting that PC 1 overexpression did not interfere with the activation of this enzyme by insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of the insulin receptor ( IR ) , insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) , and pp 60 , and phosphatidylinositol ( PI ) 3 kinase activity ( using PI as substrate ) and mitogen activated protein kinase ( MAPK ) activity were assayed in cell lysates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 phosphorylation after IGF 1 treatment was present in proliferating , quiescent , and differentiating preadipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Bradykinin also enhanced insulin stimulated GLUT 4 translocation , and insulin induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate 1 ( IRS 1 ) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells . ^^^ This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS 1 , followed by an increase in GLUT 4 translocation . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , dexamethasone down regulated insulin receptor substrate 1 protein content by 42 % and insulin induced tyrosine phosphorylation of insulin receptor substrate 1 by 28 % . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Hypertension , hypertriglyceridemia , and impaired endothelium dependent vascular relaxation in mice lacking insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was 1 . 7 fold greater , and insulin stimulated phosphoinositide 3 kinase association with IRS 1 was 2 . 3 fold higher , at 5 mM vs . 25 mM glucose . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mutation of the central Tyr 497 to Phe blocks the tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) and diminishes proliferation in response to IL 4 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is the predominant signaling molecule activated by insulin like growth factor 1 , insulin , and interleukin 4 in estrogen receptor positive human breast cancer cells . ^^^ Because insulin like growth factor 1 ( IGF 1 ) , insulin , and interleukin 4 ( IL 4 ) have known biological effects in breast cancer cells and signal through insulin receptor substrate ( IRS ) adaptor proteins , we examined the expression and function of IRS 1 and IRS 2 in breast tumors and cell lines . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Vanadate fully stimulates insulin receptor substrate 1 associated phosphatidyl inositol 3 kinase activity in adipocytes from young and old rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The high fat diet caused : ( 1 ) a 58 % decrease in insulin receptor substrate 1 ( IRS 1 ) content with a 58 % decrease in IRS 1 tyrosine phosphorylation ; ( 2 ) reductions of 56 % and 73 % respectively in insulin induced maximal PI 3 kinase activation in anti phosphotyrosine and anti IRS 1 antibody immunoprecipitates ; ( 3 ) a 46 % reduction in the glucose transporter protein , GLUT 4 content and , consequently , ( 4 ) severely impaired insulin induced GLUT 4 translocation to the plasma membrane and glucose uptake in adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In rat HTC hepatoma cells overexpressing normal human insulin receptors ( HTC IR ) , p 85 regulatory subunit of phosphatidylinositol 3 kinase ( PI3K ) forms signaling complexes containing the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , guanosine triphosphatase activating protein ( GAP ) and 60 70 kDa phosphotyrosine proteins ( p 60 70 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inhibitory action of TNF alpha was dose dependent , already detectable at 10 pmol / l , and was correlated to inhibition of tyrosine phosphorylation of IRS 1 with an unaltered autophosphorylation of the insulin receptor beta subunit . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , it prevented insulin or 5 ras induced adipocytic differentiation , utilizing a protein kinase C independent pathway . m 1 stimulation did not alter the phosphorylation state of the insulin receptor substrates IRS 1 and SHC , nor the recruitment of Grb 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The tyrosine phosphorylation of several proteins , including the beta subunit of the insulin receptor , insulin receptor substrate 1 , p 85 regulatory subunit of phosphatidylinositol 3 kinase , and ras guanosine triphosphatase activating protein , was observed in AFP+ clones , whereas the same proteins were not phosphorylated in AFP clones . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
When preadipose cells were pretreated overnight with TGFbeta , we observed a 75 % decrease in insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) compared to that in control cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Contractions do not utilize the proximal part of the insulin signalling cascade to activate glucose transport , because contractions do not cause phosphorylation of insulin receptor substrate 1 or activation of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , VS stimulated glycogen synthesis and PI 3 k were observed without any change in the tyrosine phosphorylation of insulin receptor ( IR ) beta subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphotyrosine immunoblotting and specific immunoprecipitation demonstrated that GTPgammaS did not elicit tyrosine phosphorylation of insulin receptor or insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation of proteins from RINm5F cells , using phosphotyrosine antibodies , followed by western blotting using antibody against IRS 1 revealed no distinct band of phosphorylated insulin receptor substrate ( IRS ) 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The major result of the study is that in suspended monocytes insulin induced a dose and time dependent dephosphorylation of a protein with a molecular mass of about 92 kDa without stimulating the tyrosine phosphorylation of the Insulin Receptor Substrat 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found that exposure of soleus muscles to 6 nmol / l TNF alpha for 45 min in vitro had no inhibitory effect on insulin stimulated tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 ( IRS 1 ) or on phosphatidylinositol 3 kinase association with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular scanning of the insulin receptor substrate 1 gene in subjects with severe insulin resistance : detection and functional analysis of a naturally occurring mutation in a YMXM motif . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Codon 972 polymorphism of the insulin receptor substrate 1 gene in impaired glucose tolerance and late onset NIDDM . ^^^ OBJECTIVE : To assess the relevance of a Gly > Arg substitution in codon 972 of the insulin receptor substrate 1 gene in impaired glucose tolerance ( IGT ) and NIDDM . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) and phosphatidylinositol 3 kinase ( PI 3 kinase ) are known to be involved in cellular responses to insulin such as GLUT 4 translocation , but the biochemical mechanism ( s ) connecting IRS 1 and PI 3 kinase to GLUT 4 containing intracellular membranes remains unclear . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 antisense expression in an hepatoma cell line reduces cell proliferation and induces overexpression of the Src homology 2 domain and collagen protein ( SHC ) . ^^^ 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate ( IRS ) proteins IRS 1 and IRS 2 differential signaling in the insulin / insulin like growth factor 1 pathways in fetal brown adipocytes . ^^^ In the present study we have investigated the contribution of the insulin receptor substrate proteins ( IRS 1 and IRS 2 ) to the insulin / insulin like growth factor 1 ( IGF 1 ) signaling pathways in fetal rat brown adipocytes , a model that expresses both insulin and IGF 1 receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The activated insulin receptor phosphorylates docking proteins such as Src Homology Collagen ( Shc ) and Insulin Receptor Substrate 1 ( IRS 1 ) , which then bind several proteins that contain a Src Homology 2 ( SH 2 ) domain . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The activated insulin receptor phosphorylates the intracellular substrate IRS 1 , which then binds various signalling molecules that contain SRC homology 2 domains , thereby propagating the insulin signal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Sphingomyelinase had no effect on tyrosine phosphorylation of either the insulin receptor beta subunit or the insulin receptor substrate 1 , a signaling molecule in the insulin signaling pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate 1 , 2 , and 3 , their association with p 85 phosphatidylinositol 3 kinase ( PI 3 kinase ) , and concomitantly PI 3 kinase activation via JAK 2 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
As the target substrate for insulin receptor , a Y 939 peptide consisting of 12 amino acid residues derived from insulin receptor substrate 1 ( IRS 1 ) was used . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Crk protein binds to PDGF receptor and insulin receptor substrate 1 with different modulating effects on PDGF and insulin dependent signaling pathways . ^^^ Insulin treatment of murine myoblast cells induces the formation of stable complex of endogenous c Crk with insulin receptor substrate 1 ( IRS 1 ) mediated via the SH 2 domain of Crk . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inhibition of the insulin receptor endocytosis had no effect on either the extent of insulin receptor autophosphorylation or insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although the mitogenic function of the IGF IR may require the activation of insulin receptor substrate 1 ( IRS 1 ) or IRS 2 , an overexpressed IGF IR is able to protect 32D cells , which lack IRS 1 and IRS 2 , from apoptosis caused by Interleukin 3 ( IL 3 ) withdrawal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inhibition of IGF 1 protection by ethanol corresponded to a marked reduction in the phosphorylation of insulin receptor substrate 1 , the binding of phosphatidylinositol 3 kinase ( PI 3 kinase ) , and a block of IGF 1 stimulated PI 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine residues 1250 and 1251 are not essential for tyrosine phosphorylation of two known substrates ; insulin receptor substrate 1 and SHC , nor association of known downstream adaptor proteins to these substrates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It is activated in insulin stimulated cells by binding of the Src homology 2 ( SH 2 ) domains in its 85 kDa regulatory subunit to insulin receptor substrate 1 ( IRS 1 ) , and , others . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Taken together , this study suggests that the domains of the huIL 4R alpha containing Y 497 and Y 713 positively regulate protection from apoptosis while the domain containing the STAT 6 docking sites suppresses this protection , and that additional signaling molecules other than insulin receptor substrate 1 ( IRS 1 ) , Shc , or SHIP may be involved in antiapoptotic signaling . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated cell growth in insulin receptor substrate 1 deficient ZR 75 1 cells is mediated by a phosphatidylinositol 3 kinase independent pathway . ^^^ Next , we studied insulin receptor substrate 1 ( IRS 1 ) , a major endogenous substrate for the insulin receptor which , when tyrosine is phosphorylated by the insulin receptor , interacts with and activates PI 3 K . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Analysis of the insulin signaling cascade revealed that glucosamine impaired insulin receptor autophosphorylation , insulin receptor substrate ( IRS 1 ) phosphorylation , IRS 1 associated PI 3 kinase activity in the LDM , and AKT 1 activation by insulin . ^^^ Reduction of intracellular ATP using azide inhibited Glut 1 and Glut 4 translocation from the LDM to the plasma membrane , insulin receptor autophosphorylation , and IRS 1 tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein kinase C isoforms alpha , delta and theta require insulin receptor substrate 1 to inhibit the tyrosine kinase activity of the insulin receptor in human kidney embryonic cells ( HEK 293 cells ) . ^^^ There is increasing evidence that the insulin receptor substrate 1 ( IRS 1 ) is involved in inhibitory signals in insulin receptor function . ^^^ The aim of the present study was to elucidate the role of IRS 1 in the inhibitory effects of protein kinase C on human insulin receptor function . ^^^ No effect was seen with PKC gamma , epsilon , zeta and eta while the earlier observed insulin receptor kinase inhibition of PKC beta 2 was further augmented ( 91 + / 13 % , n = 7 , p < 0 . 001 instead of 45 % without IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Forty nine families with at least two affected patients in the sibship ( 567 individuals ) were selected and tested by PCR RFLP techniques for reported mutations in 10 diabetes or obesity candidate genes : glucagon receptor , insulin receptor substrate 1 , insulin receptor , human beta 3 adrenergic receptor , fatty acid binding protein 2 , mitochondrial tRNA ( Leu ( UUR ) ) , sulphonylurea receptor , human uncoupling protein and the glycogen associated regulatory subunit of protein phosphatase 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Electron microscopic analysis , with the use of a combination of colloidal gold labelled insulin to label the insulin receptor and immunolabelling to detect caveolin or IRS 1 , demonstrated the co localisation of insulin receptors in caveolin and IRS 1 containing vesicular structures . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PTB domain of insulin receptor substrate 1 binds inositol compounds . ^^^ We examined whether a phosphotyrosine binding ( PTB ) domain from the human insulin receptor substrate 1 ( hIRS 1 ) is capable of binding inositol phosphates / phosphoinositides . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
C 2 ceramide , at concentrations which antagonized activation of both glucose uptake and Akt , had no effect on the tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) or the amounts of p 85 protein and phosphatidylinositol kinase activity that immunoprecipitated with anti IRS 1 or antiphosphotyrosine antibodies . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , in primary cultured hepatocytes stimulated with insulin , GRB 2 linked insulin receptor substrate 1 ( IRS 1 ) to dynamin 2 as well as Sos . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A novel Xenopus insulin receptor substrate cDNA was isolated by hybridization screening using the rat insulin receptor substrate 1 ( IRS 1 ) cDNA as a probe . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These data indicate that insulin potently activates integrin alpha5beta1 mediated CHO T cell adhesion , while integrin alpha5beta1 signaling in turn enhances insulin receptor kinase activity and formation of complexes containing IRS 1 and PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates the tyrosine dephosphorylation of docking protein p130cas ( Crk associated substrate ) , promoting the switch of the adaptor protein crk from p130cas to newly phosphorylated insulin receptor substrate 1 . ^^^ Insulin induced tyrosine phosphorylation of insulin receptor substrates results in the redistribution of CrkII between p 130 ( cas ) and insulin receptor substrate 1 . ^^^ A decrease in the association between CrkII and p 130 ( cas ) in response to insulin stimulation was detected in CHO cells stably expressing insulin receptor or insulin receptor substrate 1 , and in L 6 rat myoblasts . ^^^ Along with the decrease in the association of CrkII with p 130 ( cas ) , the amount of tyrosine phosphorylated insulin receptor substrate 1 co precipitated with CrkII increased in all cell types studied . ^^^ Insulin regulates the association of CrkII with p 130 ( cas ) by tyrosine dephosphorylation of p 130 ( cas ) and co ordinated tyrosine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Platelet derived growth factor inhibits insulin stimulation of insulin receptor substrate 1 associated phosphatidylinositol 3 kinase in 3T3 L 1 adipocytes without affecting glucose transport . ^^^ We found that PDGF causes serine / threonine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) in 3T3 L 1 cells , measured by altered mobility on SDS polyacrylamide gel , and this leads to a decrease in insulin stimulated tyrosine phosphorylation of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Reconstitution of insulin signaling pathways in rat 3Y1 cells lacking insulin receptor and insulin receptor substrate 1 . ^^^ Rat 3Y1 cells have endogenous insulin like growth factor 1 receptors and insulin receptor substrate ( IRS ) 2 , but lack both insulin receptor ( IR ) and IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although the tyrosine phosphorylation of insulin receptor substrate 1 was slightly reduced , correlating with a 25 % decrease in insulin receptor substrate 1 associated phosphatidylinositol 3 kinase activity , insulin stimulated Akt kinase activation was unaffected . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , GLUT 4 translocation remained unchanged for 2 h after insulin treatment , and tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) also remained constant for up to 2 h . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These effects are accompanied by a decrease in insulin stimulated tyrosine phosphorylation of IRS 1 , but insulin receptor autophosphorylation is unaltered . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated system A amino acid transport , insulin receptor ( IR ) tyrosine kinase activity , and insulin stimulated IR and IRS 1 tyrosine phosphorylation were all normal in muscles of rats fed the high fat diet for 8 weeks . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This relative ranking in the insulin mimetic potency between members of the PIG classes ( e . g . , 41 > 37 > > 7 > 1 ) was also observed for the ( 1 ) activation of glucose transport and glucose transporter isoform 4 translocation in isolated normal and insulin resistant adipocytes , ( 2 ) inhibition of lipolysis in adipocytes , ( 3 ) stimulation of glucose transport and glycogen synthesis in isolated normal and insulin resistant diaphragms , and ( 4 ) induction of tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) in diaphragms . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interestingly , we did not observe any major effects of alpha 2 HSG to inhibit insulin stimulated phosphorylation of the insulin receptor , insulin receptor substrate 1 , 2 , or 3 , in either transfected or freshly isolated adipose cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulation of insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation and the association of IRS 1 with phosphatidylinositol ( PI ) 3 kinase were not impaired by oxidative stress . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A role for insulin receptor substrate 1 in the neurotrophic action of n methyl D aspartate and its inhibition by ethanol . ^^^ The antiapoptotic action of NMDA was associated with an increase in the tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , an increase in the binding of the regulatory subunit of PI 3 kinase to IRS 1 , and a stimulation of PI 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found that overexpression of caveolin 3 augmented insulin stimulated phosphorylation of insulin receptor substrate 1 in 293T cells but not the phosphorylation of insulin receptor . ^^^ Peptides corresponding to the scaffolding domain of caveolin potently stimulated insulin receptor kinase activity toward insulin receptor substrate 1 or a Src derived peptide in vitro and in a caveolin subtype dependent fashion . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The signal generated by the insulin receptor , as reflected in the extent of insulin receptor substrate 1 tyrosine phosphorylation , was unchanged after the exercise . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The expression of a number of genes encoding key players in insulin signalling and action , including insulin , insulin receptor ( IR ) , downstream signalling molecules such as insulin receptor substrate 1 ( IRS 1 ) and IRS 2 , glucose transporters ( GLUT 4 , GLUT 2 ) and important metabolic enzymes such as glucokinase , has now been altered in transgenic or knockout mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In liver , antibodies to insulin receptor substrate 1 ( alphaIRS 1 ) , Shc or IR immunoprecipitated the three regulatory subunits of PI 3 ' kinase and an equal PI 3 ' kinase activity , without any residual activity left in the supernatants , suggesting the presence of a large complex involving IR , IRS 1 , Shc ( mainly the 52 kDa isoform ) and PI 3 ' kinase activity . ^^^ Effect of nutritional state on the formation of a complex involving insulin receptor IRS 1 , the 52 kDa Src homology / collagen protein ( Shc ) isoform and phosphatidylinositol 3 ' kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphatidylinositol 3 ' kinase associates with an insulin receptor substrate 1 serine kinase distinct from its intrinsic serine kinase . ^^^ Serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) has been proposed as a counter regulatory mechanism in insulin and cytokine signalling . ^^^ More importantly , PAS kinase dependent phosphorylation of IRS 1 reduced by 4 fold the ability of IRS 1 to act as an insulin receptor substrate . ^^^ Taken together , these findings indicate that : ( a ) PAS kinase is distinct from the intrinsic serine kinase activity of PI 3 kinase , ( b ) PAS kinase associates with the p 85 subunit of PI 3 kinase through SH 2 domain interactions , and ( c ) PAS kinase is an IRS 1 serine kinase that can reduce the ability of IRS 1 to serve as an insulin receptor substrate . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The levels of insulin receptor , as well as insulin receptor substrate 1 and phosphorylation and the association between insulin receptor substrate 1 and phosphatidylinositol 3 kinase were greater in rats fed a LP diet than in control rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The pleckstrin homology and phosphotyrosine binding domains of insulin receptor substrate 1 mediate inhibition of apoptosis by insulin . ^^^ Without IRS 1 , a chimeric insulin receptor containing a tail of tyrosine phosphorylation sites derived from IRS 1 activated the PI 3 kinase cascade but failed to inhibit apoptosis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PI 3 kinase activity precipitated with antibodies to insulin receptor substrate 1 ( IRS 1 ) and association of subunits of PI 3 kinase with IRS 1 were also increased at this stage of differentiation , suggesting that IRS 1 contributes to PI 3 kinase activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin and insulin receptor substrate 1 ( IRS 1 ) are capable of protecting liver cells from apoptosis induced by transforming growth factor beta 1 ( TGF beta ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Different subcellular distribution and regulation of expression of insulin receptor substrate ( IRS ) 3 from those of IRS 1 and IRS 2 . ^^^ Adipocytes contain three major substrate proteins of the insulin receptor , termed IRS 1 , IRS 2 , and IRS 3 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interaction of insulin receptor substrate 1 with the sigma3A subunit of the adaptor protein complex 3 in cultured adipocytes . ^^^ Signaling through the insulin receptor tyrosine kinase involves its autophosphorylation in response to insulin and the subsequent tyrosine phosphorylation of substrate proteins such as insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
MCC 555 did not modulate autophosphorylation of the insulin receptor and tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The five compounds elicited in rat adipocytes a significant increase in tyrosine phosphorylation of both insulin receptor substrate 1 ( IRS 1 ) and IRS 3 and , to a minor degree , IRS 2 , in IRS 1 / 3 associated phosphatidylinositol 3 kinase ( PI 3 K ) protein as well as activity , and in protein kinase B ( PKB ) activity as well as phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent data demonstrate that receptor positive neurons in the brain , i . e . in the hypothalamus , and secretory cells in the anterior pituitary gland possess specific proteins that are thought to be involved in key steps of post receptor signal transduction , in particular insulin receptor substrate 1 and phosphatidylinositol 3 ' kinase ( PI3k ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Plasma leptin levels : interaction of obesity with a common variant of insulin receptor substrate 1 . ^^^ A common amino acid polymorphism at codon 972 of the insulin receptor substrate 1 ( IRS 1 ) has been shown to interact with obesity in the expression of insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These results suggest that the binding of acidic motifs to the PH domain of IRS 1 and IRS 2 disrupts coupling to the activated insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin like growth factor binding protein 3 and insulin receptor substrate 1 in breast cancer : correlation with clinical parameters and disease free survival . ^^^ One of these proteins , insulin receptor substrate 1 ( IRS 1 ) , is phosphorylated after type 1 IGF receptor activation and has a major role in IGF signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Overexpression of insulin receptor substrate 1 ( IRS 1 ) in the human breast cancer cell line MCF 7 induces loss of estrogen requirements for growth and transformation . ^^^ To this end we developed several MCF 7 clones that overexpressed insulin receptor substrate 1 ( IRS 1 ) , one of the principal substrates of the IGF IR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 as a signaling molecule for focal adhesion kinase pp 125 ( FAK ) and pp 60 ( src ) . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a major substrate of insulin and insulin like growth factor 1 receptors , which upon phosphorylation on tyrosine docks several signaling molecules . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interaction of insulin receptor substrate 1 ( IRS 1 ) with phosphatidylinositol 3 kinase : effect of substitution of serine for alanine in potential IRS 1 serine phosphorylation sites . ^^^ Serine and threonine phosphorylation has been shown to down regulate insulin signaling at multiple steps , including the receptor and downstream molecules such as insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regional difference in insulin inhibition of non esterified fatty acid release from human adipocytes : relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate 1 pathway . ^^^ The mechanisms behind these site variations were investigated by comparing insulin action on NEFA metabolism with insulin receptor signal transduction through the insulin receptor substrate 1 ( IRS 1 ) pathway in omental ( visceral ) and subcutaneous human fat obtained during elective surgery . ^^^ This reduction can be explained by reduced insulin receptor autophosphorylation and signal transduction through an IRS 1 associated PI 3 kinase pathway in visceral adipocytes . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ethanol inhibits hepatocyte proliferation in insulin receptor substrate 1 transgenic mice . ^^^ Multiple growth factors promote hepatocyte proliferation , some of which involve the insulin receptor substrate 1 ( IRS 1 ) mediated signal transduction pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Clustering of beta 1 integrin also significantly potentiated stimulation of insulin receptor and IRS 1 tyrosine phosphorylation , IRS associated PI 3 kinase activity , and Akt / PKB activation caused by submaximal concentrations of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , glucose transport stimulation by DNP does not require insulin receptor substrate 1 phosphorylation and is wortmannin insensitive . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin action starts with binding to a membrane receptor ( insulin receptor tyrosine kinase ) and with activating an insulin receptor substrate 1 ( IRS 1 ) and substrate 2 ( IRS 2 ) . ^^^ The obese skeletal muscle shows a reduction of insulin receptor and IRS 1 phosphorylation and of PI 3 K activation ; the scarce expression of these proteins would determine the muscular IR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 and phosphatidylinositol 3 kinase regulate extracellular signal regulated kinase dependent and independent signaling pathways during myogenic differentiation . ^^^ We show here that insulin receptor substrate 1 ( IRS 1 ) phosphorylation on tyrosine and serine residues and association with phosphatidylinositol 3 kinase ( PI 3 kinase ) are also associated with IGF dependent myogenic differentiation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both receptors share many of the components of the PI 3 kinase signal transduction pathway , converging at the level of insulin receptor substrate 1 or insulin receptor subtrate 2 ( formally known as 4PS , or IL 4 Phosphorylated Substrate ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Since the insulin receptor ( IR ) substrate 1 ( IRS 1 ) is one of the core signaling elements transmitting mitogenic and metabolic effects of insulin , we investigated whether IRS 1 is also required for the insulin induced function of the ER . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Streptozocin induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle , including increased insulin receptor substrate 1 phosphorylation and phosphotidylinositol 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated fluid phase endocytosis ( FPE ) was examined in responsive cells , and the roles of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 ' kinase ( PI 3 ' kinase ) , Ras , and mitogen activated protein kinase kinase ( MEK ) were assessed . ^^^ The results indicate that the insulin receptor , IRS 1 , Ras , and , perhaps in certain cell types , PI 3 ' kinase are involved in mediating insulin stimulated FPE . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Finally , it was shown that the insulin receptor substrate 1 ( IRS 1 ) binding to PI 3 kinase was not sufficient for full activation because the amount of IRS 1 pulled down by the GST p 85 fusion protein reached almost maximum , after incubation with insulin treated cell lysates for 20 min , whereas PI 3 kinase activity reached its maximum only after incubation for 5 h . ^^^ They also suggest that P 13 kinase is needed to bind to other protein ( s ) as well as the insulin receptor substrate 1 for full activation . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have previously reported that endurance training increases mRNA levels of insulin receptor , IRS 1 and ERK 1 in skeletal muscle of rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The amount of insulin receptor substrate 1 ( IRS 1 ) was also higher by a factor of 2 . 6 in microsomes from refed rats ( p < 0 . 01 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor substrate 1 associates with phosphotyrosine phosphatase SHPTP 2 in liver and muscle of rats . ^^^ Insulin stimulates the tyrosine kinase activity of its receptor resulting in the phosphorylation of its cytosolic substrate , insulin receptor substrate 1 ( IRS 1 ) which , in turn , associates with proteins containing SH 2 domains . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Parenchymal cell conditioned medium did not contain any insulin like growth factor bioactivity measured as phosphorylation of type 1 insulin like growth factor receptor beta subunit and a protein with a size consistent with that of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation experiments showed that insulin like growth factor 1 receptor and insulin receptor substrate 1 were tyrosine phosphorylated to the same extent in both cells treated with colchicine and in those not exposed to the drug . ^^^ These results show that in Swiss 3T3 cells some as yet unknown events necessary for the insulin like growth factor 1 dependent activation of nuclear polyphosphoinositide metabolism require the presence of an intact cytoskeleton and are situated down stream the activation of insulin receptor substrate 1 and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphotyrosine binding domains of Shc and insulin receptor substrate 1 recognize the NPXpY motif in a thermodynamically distinct manner . ^^^ Phosphotyrosine binding ( PTB ) domains of the adaptor protein Shc and insulin receptor substrate ( IRS 1 ) interact with a distinct set of activated and tyrosine phosphorylated cytokine and growth factor receptors and play important roles in mediating mitogenic signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 ( the insulin receptor substrate 1 ) is required for signaling by both insulin and IGF 1 . ^^^ IRS 1 ( the insulin receptor substrate 1 ) is required for signaling by both insulin and IGF 1 . ^^^ Concentrations of IGF 1 high enough to cause significant binding to the insulin receptor resulted in the down regulation of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The GRB2 / Sos complex can connect with insulin receptor substrate 1 ( IRS 1 ) , which is one of the primary targets of the insulin and insulin like growth factor receptors . ^^^ In a second pathway , independent of IRS 1 , GRB 2 links the insulin receptor to Ras signaling through another adapter protein , called Shc . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After the clamp had been initiated for 30 min , the insulin stimulated phosphatidylinositol 3 kinase ( PI 3 kinase ) activities co immunoprecipitated with insulin receptor substrate 1 ( IRS 1 ) were also enhanced , resulting in increased glycogen synthase activities in the soleus muscles . ^^^ Treatment with JTT 501 also enhanced the phosphorylation of insulin receptors and insulin receptor substrate 1 rapidly as well as the phosphatidylinositol 3 kinase activities , which were stimulated by a bolus injection of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin rapidly stimulated tyrosine phosphorylation of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) and , to a lesser extent , IRS 2 in normal and diabetic myocardium . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
ET 1 treatment did not induce phosphorylation of insulin receptor beta subunit , insulin receptor substrate 1 , or Akt but stimulated the tyrosyl phosphorylation of a 75 kDa protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The cells also show a complete absence of insulin stimulated glucose transport , secondary to reduced gene expression and tyrosine phosphorylation for the insulin receptor and IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In soleus muscle from GK rats , submaximal and maximal insulin stimulated insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation and IRS 1 associated phosphatidylinositol ( PI ) 3 kinase activity were markedly reduced , compared with that of Wistar rats , but only submaximal insulin stimulated PI 3 kinase was restored after phlorizin treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cellular and molecular mechanisms of insulin resistance in isolated adipocytes from methylcholanthrene induced sarcoma bearing rats were investigated by measuring 3 O [ 14C ] methyl glucose transport activity , glucose transporter 4 ( GLUT 4 ) protein in both plasma membrane and low density microsomes , and insulin stimulated tyrosine phosphorylation of the insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
On the other hand , IGF 1 promotes the association of insulin receptor substrate 1 with the focal adhesion kinase ( FAK ) , paxillin , and the tyrosine phosphatase SHP 2 , resulting in FAK and paxillin dephosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have analyzed the association of variants in the genes for amylin , insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , and coagulation factor 5 with type 2 diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , both the tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3 kinase were enhanced in cells cultured on BM , as was the phosphorylation of the phosphatidylinositol 3 kinase effector , protein kinase B . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Modulation of insulin receptor substrate 1 tyrosine phosphorylation by an Akt / phosphatidylinositol 3 kinase pathway . ^^^ Serine / threonine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) has been implicated as a negative regulator of insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Using the same CK 2 overlay technique , another interacting protein , insulin receptor substrate 1 ( IRS 1 ) , was also identified . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We investigated the regulation of the mRNA expression of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) and p85alpha phosphatidylinositol 3 kinase ( PI 3K ) , three major actors of insulin action , in skeletal muscle from 10 healthy lean volunteers , 13 obese patients with Type 2 ( non insulin dependent ) diabetes mellitus and 7 non diabetic obese subjects . ^^^ Insulin infusion produced a twofold reduction in insulin receptor substrate 1 mRNA expression in the three groups ( p < 0 . 02 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Compared with controls , diabetic rats were characterized by multiple insulin signaling abnormalities in skeletal muscle , which included 1 ) increased insulin stimulated tyrosine phosphorylation of the insulin receptor beta subunit and insulin receptor substrates IRS 1 and IRS 2 , 2 ) increased substrate tyrosine phosphorylation in the basal state , 3 ) a decreased amount of IRS 1 protein , 4 ) markedly elevated basal and insulin stimulated phosphatidylinositol ( PI ) 3 kinase activity in anti IRS 1 immunoprecipitates from total tissue extracts , and 5 ) increased PI 3 kinase activity in low density microsomes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SB 203580 had no effect on insulin dependent insulin receptor substrate 1 phosphorylation , association of the p 85 subunit of phosphatidylinositol 3 kinase with insulin receptor substrate 1 , nor on phosphatidylinositol 3 kinase , Akt 1 , Akt 2 , or Akt 3 activities in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Oxidative stress disrupts insulin induced cellular redistribution of insulin receptor substrate 1 and phosphatidylinositol 3 kinase in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Elevated serine kinase activity was detected in Chinese hamster ovary / insulin receptor ( IR ) / IRS 1 cells and 3T3 L 1 adipocytes chronically treated with insulin , and in liver and muscle of obese JCR : LA cp rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is a target for the pure antiestrogen ICI 182 , 780 in breast cancer cells . ^^^ Here , we studied the effects of ICI 182 , 780 on IGF IR signal transduction in MCF 7 breast cancer cells and in MCF 7 derived clones overexpressing either the IGF IR or its 2 major substrates , insulin receptor substrate 1 ( IRS 1 ) or src / collagen homology proteins ( SHC ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A loss of anti lipolytic effect of pV was observed by increasing the concentration of isoprenaline and / or pV . pV induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 to a greater extent than insulin , whereas vanadate affected these components little if at all . ^^^ However , the anti lipolytic pathway of 0 . 1 mM pV did not seem to require insulin receptor substrate 1 associated PI 3K and was found to be partly independent of PDE3B . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Novel allele of the insulin receptor substrate 1 bearing two non conservative amino acid substitutions in a patient with noninsulin dependent diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
CSF 1 treated adipocytes expressing the CSF1R / IRA960 were impaired in their ability to phosphorylate insulin receptor substrate 1 ( IRS 1 ) but not in their ability to phosphorylate IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recently , it has been reported that insulin induced glucose uptake is mediated by activation of second messengers such as insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 kinase ( PI3K ) , and diacylglycerol ( DG ) protein kinase C ( PKC ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin regulates hepatocellular metabolism and growth following insulin receptor ( IR ) autophosphorylation and activation of the intracellular adapter protein , insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We find that one of the major substrates of the IGF IR , the insulin receptor substrate 1 inhibits IGF 1 mediated differentiation of 32D cells . ^^^ In the absence of insulin receptor substrate 1 , functional impairment of another major substrate of the IGF IR , the Shc proteins , is associated with a decrease in the extent of differentiation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin signalling cascade from the insulin receptor to PI 3 K was also found to be abnormal , resulting in a severely reduced phosphorylation degree of the IRS 1 ( IRS 2 ? ) PI 3 K complex , which can explain both reduced glucose transport and glycogen synthesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 enhances growth hormone induced proliferation . ^^^ In contrast , in this assay , specific insulin receptor association with the IRS 1 phosphotyrosine binding , and Shc and IRS 1 NPXY binding domains was insulin and phosphotyrosine dependent , as previously shown . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Most of its effects are mediated by the Type 1 IGF receptor ( IGF IR ) , a heterotetramer that has tyrosine kinase activity and phosphorylates insulin receptor substrates ( IRS 1 and 2 ) which leads to the activation of two downstream signaling cascades : the MAP kinase and the phosphatidylinositol 3 kinase ( P3K ) cascades . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , p 110 ( CAAX ) stimulated IRS 1 Ser / Thr phosphorylation , and inhibited IRS 1 associated PI 3 kinase activity , without affecting insulin receptor tyrosine phosphorylation , suggesting that it may play an important role as a negative regulator for insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Enhancement of insulin like growth factor signaling in human breast cancer : estrogen regulation of insulin receptor substrate 1 expression in vitro and in vivo . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mutational analysis of the insulin signalling cascade has identified a glycine arginine ( Gly Arg ) substitution at codon 972 of the insulin receptor substrate 1 ( IRS 1 ) gene with a carrier prevalence of 9 % among Caucasians . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The mechanism of activation of PI3K C2alpha by insulin differs from that of class Ia PI 3 kinases in that insulin stimulation did not cause PI3K C2alpha to associate with IRS 1 or insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To examine the molecular mechanisms associated with TNF alpha and insulin action , we measured insulin receptor substrate ( IRS ) 1 and IRS 2 mediated phosphatidylinositol 3 kinase ( PI 3 kinase ) activation , IRS 1 PI 3 kinase binding , IRS 1 tyrosine phosphorylation , and the phosphorylation of two mitogen activated protein kinases ( MAPK , known as p 42 ( MAPK ) and p 44 ( MAPK ) ) in cultured C2C12 myotubes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In skeletal muscle , insulin stimulated tyrosine phosphorylation was decreased in pregnant + / + mice , and even more so in db / + mice : insulin receptor beta ( IR beta ) , + / + 34 % , db / + 57 % decrease , P < 0 . 05 ; insulin receptor substrate 1 ( IRS 1 ) , + / + 44 % , db / + 61 % decrease , P < 0 . 05 ; and phosphoinositol ( PI ) 3 kinase ( p85alpha ) , + / + 33 % , db / + 65 % decrease , P < 0 . 05 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To address this problem we have examined the levels and phosphorylation state of the insulin receptor ( IR ) and the insulin receptor substrate 1 ( IRS 1 ) , the association between IRS 1 and the p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) as well as the PI 3 kinase activity in the livers of GH transgenic mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To determine whether glucosamine induced insulin resistance could be due to impaired signaling , we measured insulin receptor substrate ( IRS ) 1 and insulin receptor tyrosine phosphorylation ; PI 3 kinase activity associated with IRS 1 , IRS 2 , and phosphotyrosine ; and Akt activity and phosphorylation in skeletal muscle of rats infused for 2 h with glucosamine ( 6 . 0 mg 10 kg ( 1 ) 10 min ( 1 ) ) or saline . ^^^ After 1 min of insulin stimulation , phosphorylation of IRS 1 and insulin receptor increased 6 to 8 fold in saline infused rats and 7 to 10 fold in glucosamine infused rats . ^^^ Glucosamine infusion alone had no effect on tyrosine phosphorylation of the insulin receptor or IRS 1 or on stimulation of PI 3 kinase or Akt / PKB activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The PTB domains of Shc and IRS 1 both recognize autophosphorylation sites in RTKs with the consensus sequence NPXpY , but show distinct abilities to bind stably to RTKs such as the TrkA nerve growth factor receptor and the insulin receptor . ^^^ Unlike IRS 1 , the Shc PTB domain binds poorly to the insulin receptor ( IR ) beta subunit in vitro , owing to its low affinity for the NPXpY autophosphorylation site at Tyr 960 of the IR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor related receptor is expressed in pancreatic beta cells and stimulates tyrosine phosphorylation of insulin receptor substrate 1 and 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interestingly , hepatic insulin receptor substrate ( IRS ) 1 associated phosphatidylinositol 3 kinase activity was slightly elevated , but neither the content of glucose transporter GLUT 2 nor the phosphorylation state of the insulin receptor and IRS 1 were changed by acute leptin treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This lipid induced decrease in insulin stimulated muscle glucose metabolism was associated with 1 ) a approximately 50 % reduction in insulin stimulated insulin receptor substrate ( IRS ) 1 associated phosphatidylinositol ( PI ) 3 kinase activity ( P < 0 . 05 vs . control ) , 2 ) a blunting in insulin stimulated IRS 1 tyrosine phosphorylation ( P < 0 . 05 , lipid infused versus glycerol infused ) , and 3 ) a four fold increase in membrane bound , or active , protein kinase C ( PKC ) theta ( P < 0 . 05 vs . control ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this model , we have shown that : ( 1 ) lipids were incorporated in treated HepG 2 cells , but redistributed differently when compared to treated ZHC cells ; ( 2 ) that insulin signaling events , such as insulin receptor autophosphorylation and the phosphorylation of the major insulin receptor substrate ( IRS 1 ) were altered in response to the addition of membrane lipids or cholesterol derived components ; and ( 3 ) different lipids affected insulin receptor signaling differently . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Microtiter well assays for protein tyrosine phosphatase activities directed against phosphorylated insulin receptor or insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We recently identified Xenopus Rho associated protein kinase alpha ( xROKalpha ) as a Xenopus insulin receptor substrate 1 binding protein and demonstrated that the non catalytic carboxyl terminus of xROKalpha binds Xenopus insulin receptor substrate 1 and blocks insulin induced MAP kinase activation and germinal vesicle breakdown in Xenopus oocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Differential effects of ethanol on insulin signaling through the insulin receptor substrate 1 . ^^^ Insulin stimulation increases cell proliferation and energy metabolism by activating the insulin receptor substrate 1 ( IRS 1 ) signaling pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This inhibition of insulin stimulated downstream signaling occurred without any significant effect on insulin receptor autophosphorylation or tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Variables of the IGF 1 signalling pathway , including tyrosine phosphorylation of insulin receptor substrate 1 and activation of mitogen activated protein kinase and phosphatidyl inositol 3 kinase , were also augmented in mutant cells . ^^^ Insulin receptor substrate 1 message and protein abundance were higher in mutant than in control cells . ^^^ CONCLUSION / INTERPRETATION : These findings suggest that an impaired insulin signalling may upregulate insulin receptor substrate 1 and that this , in turn , leads to increased IGF 1 signalling , a phenomenon that is possibly associated with increased cell growth in diabetes . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , insulin induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 , activation of phosphatidylinositol 3 kinase , and glucose uptake were not affected by PC 1 overexpression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin receptor and insulin receptor substrate 1 contents were decreased by 14 % ( p < 0 . 05 ) and 16 % ( p < 0 . 05 ) , respectively , in skeletal muscle of obese Zucker rats . ^^^ In vivo insulin induced tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 was depressed by 82 % ( p < 0 . 05 ) and 86 % ( p < 0 . 05 ) , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A reduction in tyrosine phosphorylation of both the insulin receptor ( IR ) and the insulin receptor substrate 1 ( IRS 1 ) has been noted in both animal and human type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Corticosterone significantly decreased specific insulin binding in liver and the amount of insulin receptor substrate 1 ( IRS 1 ) and p 85 ( regulatory subunit of phosphatidylinositol ( PI ) 3 ' kinase ) in both tissues . ^^^ Insulin receptor ( IR ) and IRS 1 mRNAs generally varied accordingly . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After 2 days in G 3 medium the astrocytes were stimulated with 5 ng / ml of insulin for 2 min , and insulin effects on insulin receptor , insulin receptor substrate 1 ( IRS 1 ) and ERK 1 and 2 were studied using Western blots . ^^^ Insulin inhibited the phosphorylation of the insulin receptor and IRS 1 and decreased the activity of the ERK 1 , and inhibited the activation of the ERK 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We observed a rapid tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and an increase in Src like kinase activity in anti IRS 1 immunoprecipitates from gastrin stimulated cells , suggesting that IRS 1 may be a direct substrate of Src . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is over expressed in glycogenotic but not in amphophilic preneoplastic hepatic foci induced in rats by N nitrosomorpholine and dehydroepiandrosterone . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is over expressed in preneoplastic glycogenotic hepatic foci ( GSF ) and is gradually down regulated during progression of these lesions , via mixed cell foci ( MCF ) , to the basophilic neoplastic phenotype . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Crystal structure of the pleckstrin homology phosphotyrosine binding ( PH PTB ) targeting region of insulin receptor substrate 1 . ^^^ We have determined the crystal structure at 2 . 3 A resolution of an amino terminal segment of human insulin receptor substrate 1 that encompasses its pleckstrin homology ( PH ) and phosphotyrosine binding ( PTB ) domains . ^^^ The structural and accompanying functional data illustrate how the two binding domains might act cooperatively to effectively increase local insulin receptor substrate 1 concentration at the membrane and transiently fix the receptor and substrate , to allow multiple phosphorylation reactions to occur during each union . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we confirmed that , in In R 1 G9 cells , a pancreatic alpha cell line , insulin stimulated phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and activated phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor and IRS 1 tyrosine phosphorylation , association of the p 85 regulatory subunit of PI 3 kinase with IRS 1 , IRS 1 associated PI 3 kinase activity , and glycogen synthase activity were determined in muscle biopsy specimens taken from healthy subjects before and after insulin or exercise . ^^^ Physiological hyperinsulinemia increased the rate of glucose disposal from 11 . 4 + / 1 . 5 to 25 . 6 + / 6 . 7 micromol 10 kg ( 1 ) 10 min ( 1 ) ( P < 0 . 01 ) , insulin receptor and IRS 1 tyrosine phosphorylation ( 173 + / 19 % and 159 + / 35 % of basal values , respectively , P < 0 . 05 ) , association of the p 85 regulatory subunit of PI 3 kinase with IRS 1 ( 159 + / 10 % , P < 0 . 05 ) , and glycogen synthase fractional velocity ( 136 + / 11 % , P < 0 . 01 ) . ^^^ In contrast to insulin , exercise decreased tyrosine phosphorylation of the insulin receptor to 72 + / 10 % of basal values ( P < 0 . 05 vs basal and P < 0 . 05 vs insulin ) and had no effect on IRS 1 tyrosine phosphorylation , or association of p 85 with IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interestingly , when C57MG cells were treated with insulin , only p55PIK , but not p50PIK , bound to insulin receptor substrate 1 protein , providing evidence that different forms of p55PIKs may have specific distinct roles in signal transduction pathways . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Genetic ablation experiments of insulin receptor substrate 1 ( IRS 1 ) and 2 ( IRS 2 ) , two important molecules in the IR and IGF IR signaling pathways , are also beginning to shed light onto the mechanisms accounting for the specificity of IR and IGF IR signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Studies of the mechanisms by which free fatty acids ( FFA ) cause insulin resistance in humans indicate that increased FFA levels inhibit glucose transport , which may be a consequence of decreased insulin receptor substrate ( IRS 1 ) associated phosphatidylinositol 3 kinase activity . 13C NMR spectroscopy studies have documented that liver glycogen concentrations are reduced and the rate of hepatic gluconeogenesis is increased in subjects with type 2 diabetes ; thus , the higher rate of glucose production in type 2 diabetes can be attributed entirely to increased rates of hepatic gluconeogenesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Long term increases in PI 3 kinase activity associated with insulin receptor substrate 1 ( IRS 1 ) increased the proportion of GLUT 1 and GLUT 4 in plasma membranes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Evidence for a genetic component includes the finding of a variety of metabolic defects in various tissues in non diabetic subjects with a genetic predisposition to NIDDM , higher concordance rates for abnormal glucose tolerance including NIDDM in monozygotic compared with dizygotic twins , and the more recent demonstration of different NIDDM susceptibility genes at the sites of Insulin Receptor Substrate 1 ( IRS 1 ) , the beta 3 adrenergic receptor , and the sulfonylurea receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
At a cellular level , these metabolic effects were paralleled by inhibition of postreceptor insulin signaling critical for glucose transport and glycogen storage , including a 45 % reduction in insulin stimulated insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation ( P = 0 . 02 ) , a 44 % decrease in IRS 1 association with the p 85 regulatory subunit of phosphatidylinositol ( PI ) 3 kinase ( P = 0 . 03 ) , a 34 % reduction in IRS 1 associated PI 3 kinase activity ( P = 0 . 03 ) , and a 51 % reduction in insulin stimulated glycogen synthase activity ( P = 0 . 03 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
One cDNA that we identified encodes Dok related protein ( DokR ) , a protein with homology to p 62 ( dok ) ( Dok ) , and members of the insulin receptor substrate 1 family of proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) and their protein levels were decreased in the aorta of obese rats compared with lean rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
INR beta Myc co immunoprecipitated a phosphoprotein of 170 kDa identified as insulin receptor substrate 1 ( IRS 1 ) , whereas INR betaDelta did not , suggesting that the site of interaction was within the carboxyl terminal extension . ^^^ The carboxyl terminal extension of the Drosophila insulin receptor homologue binds IRS 1 and influences cell survival . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We report here that micromolar concentrations of H ( 2 ) O ( 2 ) dramatically inhibit insulin induced IR tyrosine phosphorylation ( pretreatment with 500 microM H ( 2 ) O ( 2 ) for 5 min inhibits insulin induced IR tyrosine phosphorylation to 8 % ) , insulin receptor substrate 1 phosphorylation , as well as insulin downstream signaling such as activation of phosphatidylinositol 3 kinase ( inhibited to 57 % ) , glucose transport ( inhibited to 36 % ) , and mitogen activated protein kinase activation ( inhibited to 7 . 2 % ) . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
The peptides contained either the YMTM motif found in insulin receptor substrate 1 ( IRS 1 ) or the YGEF motif identified from peptide library experiments to be the optimal sequence for Src . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : Total and insulin receptor substrate 1 ( IRS 1 ) associated PI 3 kinase activities were measured in skeletal muscles and adipose tissue after an intense insulin induced glucose utilization as accomplished by 90 min euglycemic hyperinsulinemic clamp . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Variants of the insulin receptor substrate 1 and fatty acid binding protein 2 genes and the risk of type 2 diabetes , obesity , and hyperinsulinemia in African Americans : the Atherosclerosis Risk in Communities Study . ^^^ The allele frequencies of the Gly972Arg variant of the insulin receptor substrate 1 ( IRS 1 ) gene and the Ala54Thr variant of the fatty acid binding protein 2 ( FABP 2 ) gene were compared in 992 normal control subjects and three patient groups : 1 ) 321 type 2 diabetic individuals , 2 ) 260 severely obese individuals , and 3 ) 258 markedly hyperinsulinemic individuals without diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Gly 972 Arg variant in the insulin receptor substrate 1 ( IRS 1 ) gene may interact with the pathogenesis of common insulin resistance disorders raising the hypothesis that the mutation may predispose to type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The protein content and the tyrosine phosphorylation state of the insulin receptor ( IR ) , the IR substrate 1 ( IRS 1 ) , the association between IRS 1 and the p 85 subunit of phosphatidylinositol ( PI ) 3 kinase , and the phosphotyrosine derived PI 3 kinase activity in this tissue were studied . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased tyrosine phosphorylation of the insulin receptor , the insulin receptor substrate 1 and a 73 kDa protein associated with insulin induced mitogenesis in SV 40 transformed 3T3T cells . ^^^ The results show that following insulin stimulation , the insulin receptor beta subunit and the insulin receptor substrate 1 undergo a much more significant tyrosine phosphorylation in CSV 3 1 cells than in 3T3T cells . ^^^ These data together indicate that the selective mitogenic effect of insulin on CSV 3 1 cells involves increased tyrosine phosphorylation of the insulin receptor , the insulin receptor substrate 1 and the 73 kDa protein , although the underlying mechanisms need to be further elucidated . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Antiinsulin receptor autoantibodies induce insulin receptors to constitutively associate with insulin receptor substrate 1 and 2 and cause severe cell resistance to both insulin and insulin like growth factor 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
JAK 1 dependent phosphorylation of insulin receptor substrate 1 ( IRS 1 ) is inhibited by IRS 1 serine phosphorylation . ^^^ Serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) reduces its ability to act as an insulin receptor substrate and inhibits insulin receptor signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In 32D cells ( a murine hemopoietic cell line devoid of insulin receptor substrate 1 [ IRS 1 ] ) , the IGF 1R activates alternative pathways for protection from apoptosis induced by withdrawal of interleukin 3 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin treatment activated the insulin receptor substrate 1 associated ( IRS 1 associated ) phosphoinositide 3 kinase ( PI 3 kinase ) 6 . 1 fold in lean , 3 . 7 fold in obese , and 2 . 4 fold in diabetic subjects . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Upon binding of insulin to cell surface insulin receptor , the receptor phosphorylates tyrosine residues of insulin receptor substrate 1 ( IRS 1 ) in the cell . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated phosphatidylinositol 3 kinase activity was further increased by PACAP 38 , whereas the tyrosine phosphorylation of insulin receptor beta subunit and insulin receptor substrate 1 was unaltered by PACAP 38 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Angiotensin 2 inhibited insulin induced egr 1 expression but not c fos expression , and the decrease in egr 1 expression was concurrent with a decrease in insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To determine whether insulin receptor substrate ( IRS ) 1 is essential for the insulin sensitizing effect of CR , we measured in vitro 2 deoxyglucose ( 2DG ) uptake in the presence and absence of insulin by skeletal muscle isolated from wild type ( WT ) mice and transgenic mice lacking IRS 1 ( knockout [ KO ] ) after either ad libitum ( AL ) feeding or 20 days of CR ( 60 % of ad libitum intake ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
On examining two lines of Tg mice identified by Southern blot , the transgene product was expressed in skeletal muscle , liver , and adipose tissues , and insulin induced association of insulin receptor substrate 1 with endogenous SHP 2 was inhibited , confirming that DeltaPTP has a dominant negative property . ^^^ Moreover , tyrosine phosphorylation of insulin receptor substrate 1 and stimulation of phosphatidylinositol 3 kinase and Akt kinase activities by insulin were attenuated in muscle and liver . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After 1 min of insulin stimulation , the insulin receptor was tyrosine phosphorylated 8 fold more and Shc was phosphorylated 50 % less in 32D cells containing both IRS 1 and insulin receptors ( 32D / IR+IRS 1 ) than in 32D cells containing only insulin receptors ( 32D / IR ) , insulin receptors and IRS 2 ( 32D / IR+IRS 2 ) , or insulin receptors and a form of IRS 1 that can not be phosphorylated on tyrosine residues ( 32D / IR+IRS 1F18 ) . ^^^ Therefore , IRS 1 and IRS 2 appeared to have different effects on insulin receptor phosphorylation and downstream signaling . ^^^ The presence of tyrosine phosphorylated IRS 1 appears to increase insulin receptor tyrosine phosphorylation and potentially tyrosine kinase activity via inhibition of protein tyrosine phosphatase ( s ) . ^^^ This effect of IRS 1 on insulin receptor phosphorylation is unique to IRS 1 , as IRS 2 had no effect on insulin receptor tyrosine phosphorylation . ^^^ Therefore , IRS 1 and IRS 2 appear to function differently in their effects on signaling downstream of the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^ 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: P06213 and P35568 Pubmed SVM Score :0.0
Phosphatidylinositol 3 kinase ( PI 3 kinase ) activity associated with hepatic insulin receptor substrate 1 ( IRS 1 ) in the insulin stimulated condition was significantly enhanced 110 % without a significant alteration in tyrosine phosphorylation of IRS 1 in the imidapril treated group . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signaling in insulin receptor substrate ( IRS ) 1 deficient brown adipocytes : requirement of IRS 1 for lipid synthesis . ^^^ Insulin receptor alpha subunit protein content and beta subunit tyrosine kinase activity remained unchanged upon insulin stimulation , regardless of the lack of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signaling [ tyrosine phosphorylation of insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , Src homology and collagen protein ( Shc ) and phosphatidyl inositol 3 ' kinase activity ( PI 3 ' kinase ) ] was studied in the liver and thigh muscles of fat ( FL ) and lean ( LL ) chickens . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The mRNA levels of insulin receptor , IRS 1 , Glut 4 , lipoprotein lipase , hormone sensitive lipase , acylation stimulating protein , fatty acid transport protein 1 , angiotensinogen , plasminogen activator inhibitor 1 , and PPARgamma 1 and gamma 2 were not modified by rosiglitazone treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The aim of this study was to determine the role of insulin receptor substrate 1 and the MAPK cascade in rats with hepatocellular carcinoma induced by 3 ' methyl 4 dimethylamino azobenzene ( 3 ' MeDAB ) . ^^^ RESULTS : Expression of insulin receptor substrate 1 ( IRS 1 ) showed a 1 . 4 fold increase at protein level in the tumors ( p < 0 . 01 ) , but the tyrosine phosphorylation of IRS 1 did not differ between the tumor and control liver . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin ( 10 ( 7 ) M , 6 h of incubation ) induced a 2 fold increase in p85alphaPI 3 K mRNA abundances ( 118 + / 12 versus 233 + / 35 amol / microgram total RNA , n = 5 , p < 0 . 01 ) without changing the expression levels of insulin receptor , IRS 1 , glycogen synthase , and Glut 4 mRNAs in differentiated myotubes from healthy subjects . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , and IRS 2 was reduced by prestimulation of beta ( 3 ) adrenergic receptors ( CL 316243 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Postnatal growth responses to insulin like growth factor 1 in insulin receptor substrate 1 deficient mice . ^^^ Organ weight was compared in adult mice with deletion of one ( IRS 1 / + ) or both ( IRS 1 / ) copies of the insulin receptor substrate 1 ( IRS 1 ) gene and IRS 1+ / + littermates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In particular , phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was evident after treatment with insulin , but not after treatment with IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We examined the gene and protein expression of IRS 1 ( insulin receptor substrate 1 ) in adipocytes from two groups of healthy individuals with an increased propensity for non insulin dependent diabetes mellitus ( NIDDM ) : those with two first degree relatives with diabetes and another group with massive obesity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In order to distinguish common and unique functions of IRS 1 , IRS 2 , and IRS 4 , we expressed them individually in 32D myeloid progenitor cells containing the human insulin receptor ( 32D ( IR ) ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Altered function of insulin receptor substrate 1 deficient mouse islets and cultured beta cell lines . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body , but its role in insulin producing beta islet cells is unclear . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of a prenylation deficient Rab 4 interferes with propagation of insulin signaling through insulin receptor substrate 1 . ^^^ Expression of a mutant Rab 4 lacking a prenylation site resulted in reduced insulin dependent phosphorylation ofcytoplasmic and internal membrane associated insulin receptor substrate 1 , leading to decreased insulin receptor substrate 1 associated phosphatidylinositol 3 ' OH kinase activation and decreased Akt activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 and associated phosphatidylinositol ( PI ) 3 kinase activity increased 2 . 5 and 3 . 5 fold after 1 and 5 days of exercise , despite reduced ( 50 % ) IRS 1 protein content after 5 days of exercise . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Supraphysiological concentration ( 1 microM ) of insulin treatment increased 2 deoxy glucose transport by up to 1 . 68 fold together with concomitant tyrosine phosphorylation of the insulin receptor beta subunit and of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To determine whether insulin receptor substrate ( IRS ) 1 , 2 , or both are involved in IGF 1 signaling in VSMCs , cell lysates were immunoprecipitated with either an anti IRS 1 or an anti IRS 2 antibody , and the associated PI 3 kinase activity was determined . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study , we have examined the implication of Ca ( 2+ ) in the phosphorylation state of the insulin receptor ( IR ) beta subunit and of insulin receptor substrate 1 ( IRS 1 ) , as well as in the stimulation of PI 3 kinase activity in cultured hepatocytes . ^^^ Insulin induced Ca ( 2+ ) entry in hepatocytes is important for PI 3 kinase activation , but not for insulin receptor and IRS 1 tyrosine phosphorylation . ^^^ Our data demonstrate that the stimulation of PI 3 kinase activity by the activated insulin receptor , but not the phosphorylation of IR beta subunit and IRS 1 , requires an influx of Ca ( 2+ ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Consistent with its involvement in TNF signaling , PI 3 kinase activities in HepG 2 and U 937 cells can be stimulated by TNF in a rapid but transient manner through a mechanism that may involve its association with the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tissue specific insulin resistance in mice with mutations in the insulin receptor , IRS 1 , and IRS 2 . ^^^ To analyze the role of the insulin signaling pathway in these processes , we have generated mice with combined heterozygous null mutations in insulin receptor ( ir ) , insulin receptor substrate ( irs 1 ) , and / or irs 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Glucosamine ( 6 h ) did not affect insulin stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 and 2 and weakly , if at all , impaired insulin stimulation of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation ( pY 939 ) by an insulin activated insulin receptor of a target peptide ( Y 939 ) derived from an insulin receptor substrate 1 ( IRS 1 ) and its subsequent binding to another downstream target , the SH 2 domain of PI 3 kinase ( SH2N ) , were detected by surface plasmon resonance ( SPR ) spectrometry . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate 1 ( IRS 1 ) associated PI 3 kinase activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine dephosphorylation and deactivation of insulin receptor substrate 1 by protein tyrosine phosphatase 1B . ^^^ However , little is known regarding the molecular interactions that influence the balance of these processes , especially the phosphorylation state of postinsulin receptor substrates , such as insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Since many receptors that activate PI3K do so through tyrosine specific protein phosphorylation , antisera to phosphotyrosine , insulin receptor substrate 1 ( IRS 1 ) , or SPAR were also examined . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin like growth factor 1 induced degradation of insulin receptor substrate 1 is mediated by the 26S proteasome and blocked by phosphatidylinositol 3 ' kinase inhibition . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a critical adapter protein involved in both insulin and insulin like growth factor ( IGF ) signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The effect of phenylephrine was not confined to signaling pathways that include insulin receptor substrate 1 , as the alpha ( 1 ) adrenergic receptor agonist also inhibited the platelet derived growth factor induced activation of PI 3 kinase and Akt 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These treatments had no effect on insulin receptor autophosphorylation or tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulation of the phosphatidylinositol 3 kinase ( PI 3 kinase ) pathway , as measured by phosphorylation of the insulin receptor and IRS 1 and by IRS protein association with p 85 and with PI 3 kinase , was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients . ^^^ Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS 1 in obese and diabetic subjects but did not increase glucose uptake or PI 3 kinase association with IRS 1 upon insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent reports have suggested that leptin can act through some of the components of the insulin signaling cascade , such as insulin receptor substrates ( IRS 1 and IRS 2 ) , phosphatidylinositol 3 kinase ( PI 3 kinase ) , and mitogen activated protein kinase , and can modify insulin induced changes in gene expression in vitro and in vivo . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein tyrosine phosphatases ( PTPases ) play a key role in maintaining the steady state tyrosine phosphorylation of the insulin receptor ( IR ) and its substrate proteins such as insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent progress suggests that postreceptor mechanisms that contribute to insulin resistance of pregnancy appear to be multifactorial , but are exerted at the beta subunit of the insulin receptor and at the level of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ethanol inhibits IGF IR tyrosine autophosphorylation , which subsequently interferes with the activation of key downstream signaling mediators including insulin receptor substrate 1 , phosphatidylinositol 3 kinase , and mitogen activated protein ( MAP ) kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Initial signalling events of insulin action , including receptor kinase activation , the tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 and IRS 2 and the recruitment of PI 3K to IRS 1 and IRS 2 , were found not to be involved in contraction mediated signalling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Since the molecular mechanism of insulin resistance is still unknown , insulin receptor dysfunction including abnormal IRS 1 phosphorylation is considered to be responsible for insulin resistance in some pathological states . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Genetic factors affecting the insulin sensitivities have been described , including the mutations of genes of insulin receptor , insulin receptor substrate 1 , glycogen synthase , uncoupling proteins , beta 3 adrenergic receptor , and peroxisome proliferator activated receptor gamma . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Effect of long term caloric restriction on GLUT 4 , phosphatidylinositol 3 kinase p 85 subunit , and insulin receptor substrate 1 protein levels in rhesus monkey skeletal muscle . ^^^ Insulin receptor substrate 1 ( IRS 1 ) abundance tended to be greater for CR compared to Control monkeys ( p = . 051 ) , but correlational analysis revealed no association between IRS 1 and insulin sensitivity ( r 2 = . 075 , p = . 271 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the latter rats , insulin receptor and insulin receptor substrate 1 protein and phosphorylation levels were elevated in liver and there was a greater association between the insulin receptor substrate 1 and p 85 subunit of phosphatidyl inositol 3 kinase compared with CO 11 rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both of these abnormalities were associated with defects in insulin activation of insulin receptor substrate 1 and 2 associated phosphatidylinositol 3 kinase activity and a 2 fold increase in muscle and liver triglyceride content . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The c Jun NH ( 2 ) terminal kinase promotes insulin resistance during association with insulin receptor substrate 1 and phosphorylation of Ser ( 307 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In muscle obtained during clamp studies prior to vanadium therapy , insulin stimulated the tyrosine phosphorylation of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , and Shc proteins by 2 to 3 fold , while phosphatidylinositol 3 kinase ( PI 3 kinase ) activity associated with IRS 1 increased 4 . 7 fold during insulin stimulation ( P = . 02 ) . ^^^ Following vanadium , there was a consistent trend for increased basal levels of insulin receptor , Shc , and IRS 1 protein tyrosine phosphorylation and IRS 1 associated PI 3 kinase , but no further increase with insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In human adipocytes , we found that insulin differentially stimulated phosphatidylinositol 3 kinase activity ; the lipid kinase activity was associated with IRS 1 , whereas the serine kinase activity was associated with the insulin receptor and phosphorylated a number of proteins including p 85 , p 110 , and a 135 kDa protein identified as PDE3B . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The two major substrates of the IGF IR , insulin receptor substrate 1 ( IRS 1 ) and the Shc proteins , are known to contribute to this activation . ^^^ The importance of the C terminus of the IGF IR in ERK activation ( in the absence of IRS 1 ) is confirmed by the failure of the insulin receptor to give a sustained activation of ERK . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Transgenic models of insulin resistance ( heterozygous insulin receptor substrate 1 knockout mice , A ZIP / F 1 fatless mice , and animals overexpressing glutamine : fructose 6 phosphate amidotransferase ) contained increased amounts of farnesylated p21Ras . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased insulin receptor substrate 1 and enhanced skeletal muscle insulin sensitivity in mice lacking CCAAT / enhancer binding protein beta . ^^^ The level of insulin receptor substrate 1 protein was increased 2 fold in skeletal muscle from C / EBPbeta ( / ) mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 in osteoblast is indispensable for maintaining bone turnover . ^^^ Insulin receptor substrates ( IRS 1 and 2 ) are essential for intracellular signaling by insulin and IGF 1 , anabolic regulators of bone metabolism . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Compared with control cells , cells expressing high levels of PTP1B showed a 50 60 % decrease in maximally insulin stimulated tyrosyl phosphorylation of IR and insulin receptor substrate 1 ( IRS 1 ) and phosphoinositide 3 kinase ( PI3K ) activity associated with IRS 1 or with phosphotyrosine . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This pathway involves stimulation of phosphatidylinositol 3 kinase ( PI3K ) binding to insulin receptor substrate 1 and insulin receptor substrate 2 , activation of PI3K and protein kinase B ( AKT ) , and PI3K dependent activation of cyclic nucleotide phosphodiesterase 3B , a cAMP degrading enzyme . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Treatment of the cells with high concentrations of glucose ( 15 33 mm ) caused phosphorylation of serine residues of the insulin receptor substrate 1 ( IRS 1 ) , leading to reduced electrophoretic mobility of it . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Roles of insulin receptor substrate 1 , phosphatidylinositol 3 kinase , and release of intracellular Ca2+ stores in insulin stimulated insulin secretion in beta cells . ^^^ In an insulin receptor substrate 1 gene disrupted beta cell tumor line , insulin did not evoke either [ Ca ( 2+ ) ] ( 1 ) changes or insulin secretion . ^^^ The data suggest that autocrine activated increases in [ Ca ( 2+ ) ] ( 1 ) are due to release of intracellular Ca ( 2+ ) stores , especially the endoplasmic reticulum , mediated by insulin receptor substrate 1 and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : We treated 3T3 L 1 adipocytes with 2 . 5 mmol / l R ( + ) alpha lipoic acid for 2 to 60 min , followed by assays of : 2 deoxyglucose uptake ; glucose transporter 1 and 4 ( GLUT 1 and GLUT 4 ) subcellular localization ; tyrosine phosphorylation of the insulin receptor or of the insulin receptor substrate 1 in cell lysates ; association of phosphatidylinositol 3 kinase activity with immunoprecipitates of proteins containing phosphotyrosine or of insulin receptor substrate 1 using a in vitro kinase assay ; association of the p 85 subunit of phosphatidylinositol 3 kinase with phosphotyrosine proteins or with insulin receptor substrate 1 ; and in vitro activity of immunoprecipitated Akt 1 . ^^^ RESULTS : Short term treatment of 3T3 L 1 adipocytes with R ( + ) alpha lipoic acid rapidly stimulated glucose uptake in a wortmannin sensitive manner , induced a redistribution of GLUT 1 and GLUT 4 to the plasma membrane , caused tyrosine phosphorylation of insulin receptor substrate 1 and of the insulin receptor , increased the antiphosphotyrosine associated and insulin receptor substrate 1 associated phosphatidylinositol 3 kinase activity and stimulated Akt activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 expression is regulated by estrogen in the MCF 7 human breast cancer cell line . ^^^ In this study we have examined the regulation of the expression of insulin receptor substrate 1 , a major intracellular substrate of the type 1 insulin like growth factor receptor tyrosine kinase . ^^^ Estradiol increased insulin receptor substrate 1 mRNA and protein levels at concentrations consistent with a mechanism involving the estrogen receptor . ^^^ Insulin receptor substrate 1 was not induced significantly by the antiestrogens tamoxifen and ICI 182 , 780 , but they inhibited the induction of insulin receptor substrate 1 by estradiol . ^^^ Analysis of tyrosine phosphorylated insulin receptor substrate 1 showed that the highest levels were found in cells stimulated by estradiol and insulin like growth factor 1 , whereas low levels were found in the absence of estradiol irrespective of whether type 1 insulin like growth factor ligands were present . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Further , insulin induced phosphorylation of downstream targets Akt and p70S6 kinase were also inhibited significantly by overexpression of PTEN , whereas tyrosine phosphorylation of the insulin receptor and IRS 1 or the phosphorylation of mitogen activated protein kinase were not affected , suggesting that the Ras / mitogen activated protein kinase pathway remains fully functional . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also studied the effect of preoperative feeding on postoperative insulin stimulated insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol ( PI ) 3 kinase activity in both Wistar rats and genetically non insulin dependent diabetic Goto Kakazaki rats ( GK rats ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
More importantly , during saline infusion SHR showed a significantly higher phosphorylation of insulin receptor substance 1 ( IRS 1 ) coupled to enhanced association of the p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) to IRS 1 and to an increased PI 3 kinase activity compared to WKY rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study we have investigated the effect of increased serine / threonine phosphorylation of insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) by okadaic acid pretreatment on brown adipocyte insulin signalling leading to glucose transport , an important metabolic effect of insulin in brown adipose tissue . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Lycopene treatment markedly reduced the IGF 1 stimulation of tyrosine phosphorylation of insulin receptor substrate 1 and binding capacity of the AP 1 transcription complex . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
For this purpose , 32D cells , which express a limited number of insulin receptors and lack endogenous bradykinin B 2 receptor ( BK2R ) or insulin receptor substrate ( IRS ) 1 were transfected with BK2R cDNA and / or insulin receptor cDNA and / or IRS 1 cDNA , and analyzed . ^^^ In 32D cells that expressed BK2R , insulin receptor and IRS 1 ( 32D BKR / IR / IRS1 ) , bradykinin also enhanced insulin stimulated tyrosine phosphorylation of the insulin receptor and IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin like growth factor 1 mediated degradation of insulin receptor substrate 1 is inhibited by epidermal growth factor in prostate epithelial cells . ^^^ We have sought to determine whether insulin like growth factor 1 ( IGF 1 ) regulates the levels of insulin receptor substrate 1 ( IRS 1 ) in prostate epithelial cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We previously showed that homozygous disruption of insulin receptor substrate 1 ( IRS 1 ) in mice resulted in insulin resistance but not diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Pretreatment with TSH or dibutyryl cAMP did not affect the IGF 1 dependent tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A study on the genetics of obesity : influence of polymorphisms of the beta 3 adrenergic receptor and insulin receptor substrate 1 in relation to weight loss , waist to hip ratio and frequencies of common cardiovascular risk factors . ^^^ Beta 3 adrenergic receptor ( beta 3 AR ) and insulin receptor substrate 1 ( IRS 1 ) have been implicated in the pathogenesis of obesity and in obesity related increase in insulin resistance which is associated with , among other diseases , dyslipidemia and type 2 diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) , as well as the association of the IRS 1 with phosphatidylinositol 3 kinase ( PI 3 kinase ) , and phosphotyrosine phosphatase ( SHP 2 ) in the liver and muscle of rats fed a control or high fructose diet for 28 d . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate proteins ( IRS 1 , 2 , 3 and 4 ) are the best studied substrates for the insulin receptor kinase ( IRK ) . ^^^ We have previously shown that IRS 1 and IRS 2 interact with the juxtamembrane ( JM ) but not with the carboxyl terminal ( CT ) region of the insulin receptor ( IR ) in vitro . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
Persistent activation of phosphatidylinositol 3 kinase causes insulin resistance due to accelerated insulin induced insulin receptor substrate 1 degradation in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Decreased GLUT 4 expression , impaired insulin receptor ( IR ) , IRS 1 , and pp60 / IRS 3 tyrosine phosphorylation are characteristics of adipocytes from insulin resistant animal models and obese NIDDM humans . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Combined use of insulin and endothelin 1 causes decrease of protein expression of beta subunit of insulin receptor , insulin receptor substrate 1 , and insulin stimulated glucose uptake in rat adipocytes . ^^^ Expression of the beta subunit of the insulin receptor ( IRbeta ) and the insulin receptor substrate 1 ( IRS 1 ) in adipocytes was not significantly affected by 1 nM insulin or by 100 nM ET 1 , even after 3 h treatment . ^^^ These results suggest that the inhibitory effect of ET 1 on ISGU may be mediated via the insulin receptor and suppression of IRbeta / IRS 1 expression . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS 1 are reduced in skeletal muscle and liver compared to SHR , due mainly to diminished expression of insulin receptor and IRS 1 proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Gly > Arg 972 amino acid polymorphism in insulin receptor substrate 1 affects glucose metabolism in skeletal muscle cells . ^^^ Molecular scanning of insulin receptor substrate 1 ( IRS 1 ) revealed several amino acid substitutions . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We investigated the relationship of codon 972 polymorphism of the insulin receptor substrate 1 ( IRS 1 ) gene with insulin resistance in the Japanese population . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 , p70S6K , and cell size in transformation and differentiation of hemopoietic cells . ^^^ After an initial burst of cell proliferation , the type 1 insulin like growth factor receptor ( IGF IR ) induces granulocytic differentiation of 32D IGF IR cells , an interleukin 3 dependent murine hemopoietic cell line devoid of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A rapamycin sensitive pathway down regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate 1 . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a major substrate of the insulin receptor and acts as a docking protein for Src homology 2 domain containing signaling molecules that mediate many of the pleiotropic actions of insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
As a consequence of IR inactivation , AT 2 receptor inhibits tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and signal regulatory protein ( SIRPalpha 1 ) and prevents subsequent association of both IRS 1 and SIRPalpha 1 with Src homology 2 ( SH 2 ) containing tyrosine phosphatase SHP 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IGF 1 induces signaling pathways that involve IGF 1 receptor mediated tyrosine phosphorylation of Shc and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Signaling molecules downstream from the insulin receptor , such as the insulin receptor substrate protein 1 ( IRS 1 ) , are also activated by other receptor tyrosine kinases . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Calorie restriction increases insulin stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 in rat skeletal muscle . ^^^ In control ( not insulin treated ) rats , there was no detectable tyrosine phosphorylation of insulin receptor ( IR ) , regardless of diet ; no diet effect on tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) or IRS 1 associated phosphatidylinositol 3 kinase ( PI3K ) protein and 21 % higher IRS 1 associated PI3K activity in AL vs . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Aberrant protein expression can not account for these insulin signaling defects because expression of insulin receptor , IRS 1 , IRS 2 , MAP kinase , or glycogen synthase was similar between type 2 diabetic and control subjects . ^^^ In skeletal muscle from type 2 diabetic subjects , IRS 1 phosphorylation , PI 3 kinase activity , and glucose transport activity were impaired , whereas insulin receptor tyrosine phosphorylation , MAP kinase phosphorylation , and glycogen synthase activity were normal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We conclude the following : 1 ) physiological hyperinsulinemia induces sustained activation of insulin signaling molecules in human skeletal muscle ; 2 ) the more distal insulin signaling components ( Akt , GSK 3 ) are activated much more rapidly than the proximal signaling molecules ( IRTK as well as insulin receptor substrate 1 and phosphatidylinositol 3 kinase [ Wojtaszewski et al . , Diabetes 46 : 1775 1781 , 1997 ] ) ; and 3 ) prior exercise increases insulin stimulation of both glucose uptake and glycogen synthase activity in the absence of an upregulation of signaling events in human skeletal muscle . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The relative phosphotyrosine ( Tyr ( P ) ) contents of the insulin receptor and its substrate 1 ( IRS 1 ) were assessed in whole cell homogenates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphoinositide 3 kinase ( PI3K ) activity associated with insulin receptor substrate ( IRS ) 1 or phosphotyrosine was reduced 67 86 % in tissues of obese rats because of lower IRS 1 protein levels and reduced insulin receptor and IRS 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor substrate 1 , phosphatidylinositol 3 kinase , protein kinase B , and glycogen synthase was normal in the relative cultures with impaired insulin responsiveness . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Exercise training prevents maturation induced decreases in insulin receptor substrate 1 and phosphatidylinositol 3 kinase in rat skeletal muscle . ^^^ The concentration of mRNA and protein for insulin receptor substrate 1 ( IRS 1 ) in sedentary rats significantly decreased with maturation ( 49 % and 63 % , respectively , at age 27 weeks 5 age 4 weeks ) , but in trained rats they did not decrease with maturation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Dexamethasone induces overexpression of the PI3K subunit p85alpha , which , in turn , competes with the complete PI3K heterodimer for binding at insulin receptor substrate 1 , inhibiting PI3K activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The mechanism of this inhibition involves the activation of the `` classical ' ' protein kinase C isoforms and the serine phosphorylation of insulin receptor and IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Relative to non diabetic control rats ( WKY ) , insulin stimulated insulin receptor ( IR ) autophosphorylation and insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation were significantly inhibited in GK skeletal muscles . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin binding and protein levels of insulin receptor substrate 1 ( IRS 1 ) , p 85 subunit of phosphatidylinositol 3 ' kinase ( p 85 ) and Src homology 2 domain containing phosphatase 2 ( SHP 2 ) were then determined in hindlimb muscle and liver . ^^^ Additionally , protein tyrosine phosphatase ( PTPase ) activities towards immobilized phosphorylated insulin receptor or phosphorylated IRS 1 of membrane ( MF ) and cytosolic fractions ( CF ) of these tissues were measured . ^^^ Ramipril treatment also increased dephosphorylation of insulin receptor by muscle CF ( 22 . 0+ / 1 . 0 % / 60 min compared to 16 . 8+ / 1 . 5 % / 60 min ; P < 0 . 05 ) , and of IRS 1 by liver MF ( 37 . 2+ / 1 . 7 % / 7 . 5 min compared to 33 . 8+ / 1 . 7 % / 7 . 5 min ; P < 0 . 05 ) and CF ( 36 . 8+ / 1 . 0 % / 7 . 5 min compared to 33 . 2+ / 1 . 0 % / 7 . 5 min ; P < 0 . 05 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In L6hIR cells , inhibition of insulin receptor substrate 1 ( IRS 1 ) expression caused a 90 % decrease in insulin induced PKCalpha and beta activation and blocked insulin stimulation of mitogen activated protein kinase ( MAPK ) and DNA synthesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Variability of the insulin receptor substrate 1 , hepatocyte nuclear factor 1alpha ( HNF 1alpha ) , HNF 4alpha , and HNF 6 genes and size at birth in a population based sample of young Danish subjects . ^^^ The Gly / Arg972 of insulin receptor substrate 1 ( IRS 1 ) , the Thr / Ile130 of the hepatocyte nuclear factor 4alpha ( HNF 4alpha ) , the Pro / Ala75 of HNF 6 , and the Ile / Leu27 , Ala / Val93 , and Ser / Asn4s7 polymorphisms of the HNF lalpha gene were examined for association with birth weight and length and the ponderal index . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To determine the importance of this distribution to IRS 1 mediated signaling , we constructed a prenylated , constitutively membrane bound IRS 1 by adding the COOH terminal 9 amino acids from p 21 ( ras ) , including the CAAX motif , to IRS 1 ( IRS CAAX ) and analyzed its function in 32D cells expressing the insulin receptor . ^^^ Hence , tight association with the membrane increased IRS 1 serine phosphorylation and reduced coupling between the insulin receptor , PI3 ' kinase , and proliferative signaling while enhancing other signaling pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 mediated enhancement of growth hormone induced mitogen activated protein kinase activation . ^^^ Interaction of GH with the cell surface GH receptor ( GHR ) causes activation of the GHR associated tyrosine kinase , JAK 2 , and consequent triggering of signaling cascades including the STAT , Ras / Raf / MEK1 / MAP kinase , and insulin receptor substrate 1 ( IRS 1 ) / PI3kinase pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cell adhesion and focal adhesion kinase regulate insulin receptor substrate 1 expression . ^^^ Here we show that cell adhesion regulates insulin receptor substrate 1 ( IRS 1 ) mRNA synthesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The abundance and tyrosine phosphorylation state of the insulin receptor ( IR ) , the IR substrate 1 ( IRS 1 ) , and Shc , the association between IRS 1 and the p 85 subunit of phosphatidylinositol ( PI ) 3 kinase , the IRS 1 and the phosphotyrosine associated PI 3 kinase in liver were examined . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor and insulin receptor substrate 1 in rat retinae . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a major cytosolic substrate of the insulin receptor Expression of insulin receptor and IRS 1 , and the distribution of these components of the insulin signalling pathway , were investigated in rat retinae . ^^^ Insulin receptor and IRS 1 were located in retinal sections with anti insulin receptor and anti IRS 1 antibodies . ^^^ Reverse transcription polymerase chain reaction ( RT PCR ) of retinal mRNA was performed with primers specific for insulin receptor and IRS 1 gene sequences . ^^^ Immunohistochemistry demonstrated distinct but closely associated staining patterns for insulin receptor and IRS 1 throughout rat retinae . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Since insulin is a key hormone for adipocyte conversion , and IRS 1 ( insulin receptor substrate 1 ) and Shc ( Src homology collagen ) proximal intracellular substrates of the insulin receptor control cell proliferation , the aim of this study was to investigate the role of IRS 1 and Shc in the early steps of differentiation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Genotype phenotype correlations in first degree relatives of an index case caring the Type A syndrome , suggested that association of allelic variants of IRS 1 and IRS 2 with insulin receptor mutations contribute , by synergistic effects , to phenotypic expression of defects in signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The differentiation of human adipocytes was characterized by a two to threefold stimulation of glucose transport in response to insulin and a marked increase protein expression for the insulin receptor , IRS 1 , GLUT 4 , PI 3 kinase , and PKB , with respect to undifferentiated cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The protein tyrosine kinase fer associates with signaling complexes containing insulin receptor substrate 1 and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Subsequent basal and insulin induced phosphorylation of the insulin receptor , IRS 1 , MAPK , Akt kinase , and GSK 3 were similar in control and pretreated cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Cloning and characterization of PHIP , a novel insulin receptor substrate 1 pleckstrin homology domain interacting protein . ^^^ Insulin receptor substrate 1 ( IRS 1 ) protein is a major substrate of the insulin receptor tyrosine kinase and is essential for transducing many of the biological effects of insulin including mitogenesis , gene expression , and glucose transport . ^^^ The N terminus of IRS 1 contains a pleckstrin homology ( PH ) domain that is critical for recognition and subsequent phosphorylation of IRS 1 by the activated insulin receptor . ^^^ We conclude that PHIP represents a novel protein ligand of the IRS 1 PH domain that may serve to link IRS 1 to the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Downstream of IGF IR , insulin receptor substrate 1 was phosphorylated , leading to the activation of phosphatidylinositol 3 ' kinase ( PI 3K ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular scanning for mutations in the insulin receptor substrate 1 ( IRS 1 ) gene in Mexican Americans with Type 2 diabetes mellitus . ^^^ BACKGROUND : Insulin receptor substrate 1 ( IRS 1 ) is an endogenous substrate for the insulin receptor tyrosine kinase , which plays an important role in insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found that IGF 1 stimulation enhanced tyrosine phosphorylation of two proteins , beta catenin and insulin receptor substrate 1 , which formed a complex with E cadherin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 and glucose transporter gene polymorphisms in noninsulin dependent diabetes mellitus ] . ^^^ OBJECTIVE : To evaluate the role of insulin receptor substrate 1 ( IRS 1 ) and glucose transporter 1 ( GLUT 1 ) gene polymorphisms in Chinese patients with noninsulin dependent diabetes mellitus ( NIDDM ) and diabetic neophropathy ( DN ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 ( IRS 1 ) , thereby diminishing subsequent insulin induced tyrosine phosphorylation of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Subsequently 125I insulin binding to the cells and the effects of insulin stimulation on insulin receptor substrate 1 phosphorylation , association of phosphatidylinositol 3 kinase with insulin receptor substrate 1 and Akt Thr 308 phosphorylation were measured . ^^^ RESULTS : In cells not exposed to indinavir , insulin ( 100 nmol / l ) led to rapid increases of insulin receptor substrate 1 phosphorylation , association of phosphatidylinositol 3 kinase with insulin receptor substrate 1 and Akt phosphorylation during the first 75 s , followed by subsequent decreases . ^^^ In indinavir treated cells , these insulin stimulated increases during the first 75 s were reduced by 30 60 % and this was not associated with alterations in cell number or viability , insulin binding to the cells or cellular insulin receptor substrate 1 content . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , we found that the Box 1 region and the C terminal tail of IL 13R alpha 1 were critical for binding to Tyk 2 , and activation of Jak 1 , Tyk 2 , the insulin receptor substrate 1 and STAT 6 respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also observed that silibinin reduced insulin receptor substrate 1 tyrosine phosphorylation , indicating an inhibitory effect on the insulin like growth factor 1 receptor mediated signaling pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
ET 1 treatment did not induce phosphorylation of insulin receptor beta ( IRbeta ) , insulin receptor substrate 1 ( IRS 1 ) or Akt , but stimulated the phosphorylation of extracellular signal regulated kinase ( ERK1 / 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin also increased tyrosine phosphorylated insulin receptor substrate 1 and phosphatidylinositol 3 kinase adapter ( p 85 ) subunit contents in the intracellular membrane fraction , but these signaling molecules were not directly associated with GLUT 4 vesicles . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The mechanisms giving rise to decreased insulin signalling include serine / threonine phosphorylation of insulin receptor substrate 1 , but also direct inhibition of components such as PKB . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
OBJECTIVE : We compared the insulin mimetic effects of vanadate , a protein tyrosine phosphatase inhibitor , with the effects of insulin on skeletal muscle glucose transport and insulin receptor and insulin receptor substrate 1 phosphorylation to test the hypothesis that protein tyrosine phosphatases participate in pregnancy induced insulin resistance . ^^^ Insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation were measured , as was 2 deoxyglucose transport . ^^^ In muscle tissues from pregnant control subjects vanadate increased tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 to levels similar to those in muscle tissues from nonpregnant control subjects . ^^^ In patients with gestational diabetes mellitus vanadate increased insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation , but these values remained less than in muscle tissues from nonpregnant control subjects ( P < . 05 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of SHP 2 by PKA resulted in a dramatic stimulation of phosphatase activity measured either with insulin receptor substrate 1 or with the synthetic peptide [ ( 32 ) P ] poly ( Glu / Tyr ) as substrate . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Chronic activation of insulin receptor signaling by IRS 1 overexpression in the beta cell inhibited gene expression of SERCA 3 , an endoplasmic reticulum Ca ( 2+ ) ATPase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Down regulation of insulin like growth factor 1 receptor and insulin receptor substrate 1 expression in advanced human breast cancer . ^^^ We investigated the expression pattern of insulin like growth factor 1 receptor ( IGF IR ) , insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) , a core downstream signaling protein , in 69 primary breast cancer specimens of different grades and in 21 control tissues by immunohistochemistry . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp 185 , which contains insulin receptor substrates IRS 1 and IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 3 ( IRS 3 ) and IRS 4 impair IRS 1 and IRS 2 mediated signaling . ^^^ To investigate the roles of insulin receptor substrate 3 ( IRS 3 ) and IRS 4 in the insulin like growth factor 1 ( IGF 1 ) signaling cascade , we introduced these proteins into 3T3 embryonic fibroblast cell lines prepared from wild type ( WT ) and IRS 1 knockout ( KO ) mice by using a retroviral system . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The enhanced insulin stimulated increases in ERK and glycogen synthase activities in KO mice were not associated with higher insulin receptor or with IRS 1 tyrosine phosphorylation or with IRS 1 binding to phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Essential role of insulin receptor substrate 1 in differentiation of brown adipocytes . ^^^ The most widely distributed members of the family of insulin receptor substrate ( IRS ) proteins are IRS 1 and IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : In a case control study on 320 male patients and 962 male healthy controls we investigated the association of two candidate genes with diabetes , i . e . ( 1 ) the GNB 3 825T allele , associated with a G protein beta 3 subunit splice variant and enhanced intracellular signal transduction , and ( 2 ) the insulin receptor substrate 1 ( IRS 1 ) 972Arg variant , which encodes a protein variant associated with cellular insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor and insulin receptor substrate 1 and 2 was decreased 44 % ( P < 0 . 05 ) , 57 % ( P < 0 . 001 ) , and 77 % ( P < 0 . 001 ) , respectively , in trained vs . untrained muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These responses are largely mediated downstream of the insulin receptor substrates , IRS 1 and IRS 2 ( refs 4 8 ) , through distinct signalling pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Importantly , signaling molecules such as IGF IR , insulin receptor , and insulin receptor substrate 1 , leading to the MAP kinase pathway , were found to be concomitantly overexpressed within certain tumor lines , i . e . , MCF 7 and T 47D . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , evidence points also to both phosphatidylinositol 3 kinase , which binds to the tyrosine phosphorylated insulin receptor substrate 1 , and the Ras complex in insulin ' s downstream signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin and IGF 1 stimulated PI 3 K activity was mainly associated with insulin receptor substrate ( IRS ) isoforms IRS 1 and IRS 2 and less so with the IRS isoform Grb 2 associated binder 1 ( Gab 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PACAP 38 further increased insulin stimulated phosphatidylinositol ( PI ) 3 kinase activity , but has not effect on tyrosine phosphorylation of insulin receptor beta subunit or IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Signal transducer and activator of transcription ( STAT ) induced STAT inhibitor 1 ( SSI 1 ) / suppressor of cytokine signaling 1 ( SOCS 1 ) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 ( IRS 1 ) phosphorylation . ^^^ While the forced expression of SSI 1 reduced the phosphorylation level of insulin receptor substrate 1 ( IRS 1 ) , SSI 1 deficiency resulted in sustained phosphorylation of IRS 1 in response to insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation revealed that a PI 3 kinase regulatory subunit , p85alpha , was associated with insulin receptor substance 1 ( IRS 1 ) phosphorylated by H2O2 treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The latter was accompanied by a decrease in the phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and the association of IRS 1 with Grb2 / Sos , without affecting the phosphorylation status of the insulin receptor and Shc , nor Shc / Grb2 complex formation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This may possibly occur through inhibition of insulin receptor ( IR ) tyrosine kinase activity mediated by serine / threonine phosphorylation of the IR or insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Four members ( IRS 1 , IRS 2 , IRS 3 and IRS 4 ) of this family have been identified that differ in tissue distribution , subcellular localisation , developmental expression , binding to the insulin receptor and interaction with SH 2 domain containing proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association of insulin receptor substrate 1 ( IRS 1 ) y 895 with Grb 2 mediates the insulin signaling involved in IRS 1 deficient brown adipocyte mitogenesis . ^^^ We have recently generated immortalized fetal brown adipocyte cell lines from insulin receptor substrate 1 ( IRS 1 ) knockout mice and demonstrated an impairment in insulin induced lipid synthesis as compared to wild type cell lines . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Essential role of insulin receptor substrate 1 ( IRS 1 ) and IRS 2 in adipocyte differentiation . ^^^ To investigate the role of insulin receptor substrate 1 ( IRS 1 ) and IRS 2 , the two ubiquitously expressed IRS proteins , in adipocyte differentiation , we established embryonic fibroblast cells with four different genotypes , i . e . , wild type , IRS 1 deficient ( IRS 1 ( / ) ) , IRS 2 deficient ( IRS 2 ( / ) ) , and IRS 1 IRS 2 double deficient ( IRS 1 ( / ) IRS 2 ( / ) ) , from mouse embryos of the corresponding genotypes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Receptor neutralization studies and measurements of insulin receptor substrate 1 phosphorylation confirm that the enhanced growth of D 9 cells is due to increased stimulation of the IGF 1 and insulin receptors by IGF 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This inhibition was not due to impaired insulin receptor substrate 1 phosphorylation or a loss in phosphoinositide 3 kinase activation but was caused by a failure to activate protein kinase B . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , activation of IRS 1 associated phosphatidylinositide 3 kinase , and phosphorylation of protein kinase B / Akt 1 were not inhibited by nocodazole treatment indicating that the microtubule network was not required for proximal insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin injection resulted in normal tyrosyl phosphorylation of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) in muscle of transgenic mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Et 3 , 4 dephostatin increased the tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 with or without insulin in differentiated 3T3 L 1 mouse adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
When the concentrations of insulin receptor substrate 1 ( IRS 1 ) , a major substrate of the IGF IR , are high , the signal is mitogenic , anti apoptotic , and can even cause malignant transformation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Oestradiol enhances IGF 1R signalling by inducing the expression of insulin receptor substrate 1 ( IRS 1 ) , a substrate of the IGF 1R . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
MEASUREMENTS AND MAIN RESULTS : In liver of rats with sustained endotoxemia , there were significant decreases in insulin stimulated tyrosine phosphorylation of insulin receptors ( 74 % ) , insulin receptor substrate ( IRS ) 1 ( 74 % ) , and IRS 2 ( 53 % ) ; binding of the p 85 subunit of phosphatidylinositide 3 kinase to IRS 1 ( 80 % ) ; and IRS 1 precipitable phosphatidylinositide 3 kinase activity ( > 90 % ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In a set of in vivo experiments , the levels of alpha subunit of the insulin receptor , the insulin receptor substrate 1 ( IRS 1 ) and the phosphatidylinositol 3 kinase ( PI3K ) were determined . [ 3H ] thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Exposure of these cells to EPA caused up regulation of several insulin induced activities including tyrosine phosphorylation of insulin receptor substrate 1 , insulin receptor substrate 1 associated phosphatidylinositol 3 kinase , and its downstream target Akt kinase activity as well as down regulation of gluconeogenesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To test the applicability of this split luciferase complementation , we used insulin induced interaction between known binding partners , phosphorylated insulin receptor substrate 1 ( IRS 1 ) and its target N terminal SH 2 domain of PI 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After IGF 1 stimulation , insulin receptor substrate 1 and 2 phosphorylation and PI3K activity were restored to levels similar to or greater than those seen in wild type cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A 10 min exposure to homocysteine thiolactone ( 50 microM ) resulted in a significant inhibition of insulin stimulated tyrosine phosphorylation of the insulin receptor beta subunit and its substrates IRS 1 and p 60 70 , as well as their association with the p 85 regulatory subunit of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
EIR Y1158F was impaired in its ability to phosphorylate insulin receptor substrate ( IRS ) 1 and induce downstream signals of IRS 1 phosphorylation , such as the association of IRS 1 with phosphatidyl inositol 3 ' kinase and the activation of protein kinase B ( Akt ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we demonstrated that chronic GH treatment of differentiated 3T3 L 1 adipocytes reduces insulin stimulated 2 deoxyglucose ( DOG ) uptake and activation of Akt ( also known as protein kinase B ) , both of which are downstream effects of phosphatidylinositol ( PI ) 3 kinase , despite enhanced tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 , association of IRS 1 with the p 85 subunit of PI 3 kinase , and IRS 1 associated PI 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In several clones of these cells ( B 2 , F 4 ) , insulin dependent binding of the KRLB to insulin receptors was accompanied by a block of IRS 2 , but not IRS 1 , phosphorylation , and insulin receptor binding . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin independent and wortmannin resistant targeting of IRS 3 to the plasma membrane via its pleckstrin homology domain mediates a different interaction with the insulin receptor from that of IRS 1 . ^^^ RESULTS : In contrast to IRS 1 , IRS 3 was tyrosine phosphorylated by the insulin receptor altering Tyr 960 to Phe ( Y960F ) , which disrupts the binding site of the PTB domain of IRSs , to an extent comparable to the wild type receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Biochem . 268 , 25 34 ] , epidermal growth factor ( EGF ) gave rise to transient tyrosine phosphorylation of insulin receptor substrates ( IRS 1 and IRS 2 ) , thereby activating the bound phosphatidylinositol 3 kinase in human epidermoid carcinoma A 431 cells normally abundant in EGF receptors ( EGFR ) and Chinese hamster ovary ( CHO ) cells transfected with full length EGFR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Time course analysis of insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol ( PI ) 3 kinase activity revealed that incubation with amino acids speeds up its time dependent deactivation , leading to a dramatic suppression ( 70 % ) of its activity after 30 min of insulin stimulation as compared with its maximal activation ( 5 min of stimulation ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor and IRS 1 in response to insulin challenge in vivo was markedly amplified in fat and skeletal muscle expressing Q205L Galpha ( i 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We recently showed that a high fructose diet containing vegetable oil but a normal sodium / potassium ratio induced mild insulin resistance with decreased insulin receptor substrate 1 tyrosine phosphorylation in the liver and muscle of normal rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Previous studies have shown that E 2 or progesterone can regulate the relative abundance of insulin receptor substrate 1 and 2 in cells and tissues . ^^^ Insulin receptor substrate 2 protein was diminished in uteri of E 2 treated insulin receptor substrate 1 null mutant mice , but not in E 2 treated IGF 1 null mutant mice . ^^^ Collectively , these data suggest that the E 2 induced decrease in uterine insulin receptor substrate 2 requires IGF 1 signaling , is not dependent solely on insulin receptor substrate 1 and PI3K , and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We therefore tested the C2C12 myogenic cell line for its response to GH and demonstrate that C2C12 skeletal muscle cells rapidly respond to physiological levels of GH with increased tyrosine phosphorylation of the GH receptor , Janus kinase 2 , signal transducer and activator of transcription 5a and 5b , insulin receptor substrate 1 , and activation of MAPKs / ERKs and protein kinase B / Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The role of the insulin receptor substrate 1 in the differentiation of rat hippocampal neuronal cells . ^^^ H 19 7 / IGF IR cells have low levels of expression of insulin receptor substrate l ( IRS 1 ) , a major substrate of the IGF IR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 pleckstrin homology and phosphotyrosine binding domains are both involved in plasma membrane targeting . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A receptor binding assay based on the surface plasmon resonance ( SPR ) biosensor technique was developed to study the interaction between insulin like growth factor 1 receptor ( IGF 1R ) and its intracellular substrate protein insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In estrogen receptor ( ER ) positive breast tumors , the levels of the IGF IR and its substrate , insulin receptor substrate 1 ( IRS 1 ) , are often elevated , and these characteristics have been linked with increased radioresistance and cancer recurrence . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
By activating the Insulin receptor ( IR ) > IRS 1 > phosphatidylinositol 3 kinase ( PI3K ) > Akt pathway , insulin protects vascular smooth muscle cells ( VSMC ) from undergoing apoptosis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
DESIGN AND METHODS : Phosphatidylinositol 3 kinase ( PI 3 kinase ) activity , insulin receptor substrate 1 ( IRS 1 ) associated tyrosine phosphorylation , and p 85 subunit of PI 3 kinase were measured in VSMC from SHR and normotensive Wistar Kyoto ( WKY ) rats in the absence and presence of Ang 2 type 1 receptor antagonist RNH 6270 and mitogen activated protein kinase / extracellular signal regulated kinase ( MEK ) inhibitor U 0126 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we examine the hypothesis that differential phosphorylation of insulin receptor substrate 1 ( IRS 1 ) may contribute to these differences in signalling between the two receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Gab 2 , an adaptor protein of the insulin receptor substrate 1 family , has been shown to be involved in the downstream signaling from cytokine receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , insulin receptor substrate 1 ( IRS 1 ) phosphorylation and IRS 1 associated phosphatidylinositol ( PI ) 3 kinase activity was significantly reduced , 30 50 % , in FFA 1 rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Muscle levels of insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 kinase ( PI3K ) , and Akt 1 , a serine threonine kinase , were determined . ^^^ Exercise training eliminates age related differences in skeletal muscle insulin receptor and IRS 1 abundance in rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Since caveolae may be important sites for crosstalk between tyrosine kinase and sphingolipid signaling pathways , we examined the role of increased caveolar pools of ceramide in regulating tyrosine phosphorylation of the IR and its main substrate , insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We examined the abundance and degree of tyrosine phosphorylation of the insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , and IRS 2 in skeletal muscle and , for comparison , liver . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Muscle insulin receptor was increased , but phosphotyrosine associated phosphatidylinositol 3 kinase activity stimulated by insulin was lower in undernourished rats , whereas insulin receptor substrate 1 content remained unaltered . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin signaling cascade , insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we show that in COS 7 cells SOCS 3 decreases insulin induced insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation and its association with p 85 , a regulatory subunit of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Preincubation of cells with leptin also had no effect on insulin stimulated tyrosine phosphorylation of insulin receptor , IRS 1 and IRS 2 , phosphatidylinositol 3 kinase activity , or Akt phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IGF 1 activates phosphatidylinositol 3 kinase ( PI 3 kinase ) and extracellular signal regulated MAPK pathways in A 10 cells , although insulin receptor substrate 1 ( IRS 1 ) associated PI 3 kinase is more closely linked to IGF 1 induced proliferation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of Ser 307 in insulin receptor substrate 1 blocks interactions with the insulin receptor and inhibits insulin action . ^^^ Serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) inhibits insulin signal transduction in a variety of cell backgrounds , which might contribute to peripheral insulin resistance . ^^^ During a yeast tri hybrid assay , phosphorylation of Ser ( 307 ) by JNK 1 disrupted the interaction between the catalytic domain of the insulin receptor and the PTB domain of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Four members ( IRS 1 , IRS 2 , IRS 3 , IRS 4 ) of this family have been identified that differ as to tissue distribution , subcellular localization , developmental expression , binding to the insulin receptor , and interaction with SH 2 domain containing proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin is an important regulator of growth and initiates its action by binding to its receptor , which undergoes tyrosyl autophosphorylation and further enhances its tyrosine kinase activity towards other intermediate molecules , including insulin receptor substrate 1 , insulin receptor substrate 2 , and Shc . ^^^ It was also observed that acute stimulation with insulin can induce tyrosyl phosphorylation of insulin receptor , that the insulin receptor substrates and Shc proteins serve as signaling molecules for insulin in skin of rats , and that insulin is able to induce association of insulin receptor substrate 1 / phosphatidylinositol 3 kinase and Shc / growth factor receptor bound protein 2 in this tissue , as well as phosphorylation of mitogen activated protein kinase and serine threonine kinase , demonstrating that proteins involved in early steps of insulin action are expressed in skin of intact rats and are quickly activated after insulin stimulation . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Skeletal muscle insulin resistance in normoglycemic subjects with a strong family history of type 2 diabetes is associated with decreased insulin stimulated insulin receptor substrate 1 tyrosine phosphorylation . ^^^ In contrast , the FH ( + ) group had decreased insulin stimulation of insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation ( 0 . 522 + / 0 . 077 vs . 1 . 328 + / 0 . 115 density units ; P < 0 . 01 ) and association of PI 3 kinase activity with IRS 1 ( 0 . 299 + / 0 . 053 vs . 0 . 466 + / 0 . 098 activity units ; P < 0 . 05 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association of a polymorphism in the gene of insulin receptor substrate 1 , an essential substrate in insulin signaling , with the extent of ossification was evaluated with genomic DNA extracted from the overall study group . ^^^ However , no significant association was seen between the insulin receptor substrate 1 polymorphism and the extent of ossification . ^^^ Since insulin receptor substrate 1 is expressed both in the spinal ligament and in the tissues regulating glucose metabolism , we speculate that some other molecules related to insulin signaling that are impaired only in the tissues regulating glucose metabolism may be responsible for the progression of ossification . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
TNF alpha also down regulates insulin stimulated glucose uptake via effects on glucose transporter 4 , insulin receptor autophosphorylation and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Serine phosphorylation of insulin receptor substrate 1 : a novel target for the reversal of insulin resistance . ^^^ Serine phosphorylation of insulin receptor substrate 1 seems prominent among the mechanisms of TNFalpha induced insulin resistance . ^^^ Recent advances indicate that serine kinases may phosphorylate and thus inhibit the tyrosine phosphorylation of insulin receptor substrate 1 , revealing an integration point of TNFalpha and insulin signaling pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
On the other hand , the association with insulin resistance of a common polymorphism ( Gly972Arg ) in the insulin receptor substrate 1 , long believed to be a plausible candidate gene , is weak at best . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also studied the effects of C peptide on insulin receptor autophosphorylation , its tyrosine kinase activity , phosphorylation of IRS 1 , PI 3 kinase , Akt , p90Rsk , MAPK , and GSK 3 in these cells . ^^^ RESULTS : In L 6 cells , physiological concentrations of C peptide ( 0 . 3 3 nmol / l ) significantly activated insulin receptor tyrosine kinase , IRS 1 tyrosine phosphorylation , PI 3 kinase activity , MAPK phosphorylation , p90Rsk , and GSK 3 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
RESULTS : The early events of insulin signalling including tyrosine phosphorylation of the insulin receptor and IRS 1 , IRS 1 association with the p 85 subunit , and PI 3 kinase activity were not affected by expression of WT and Delta IP SHIP 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We investigated the effects of dietary restriction on aging dependent changes in plasma level of IGF 1 and gene expression levels of type 1 IGF receptor ( IGFR ) , insulin receptor substrate 1 ( IRS 1 ) , and IGF 1 in the diaphragm and quadriceps femoris muscle ( QFM ) of male F 344 rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Pretreatment with angiotensin 2 markedly inhibited insulin stimulated tyrosine phosphorylation of insulin receptor beta chain and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We show here that phosphorylation of the insulin receptor and insulin receptor substrate 1 is increased when suspended cells are replated on fibronectin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also demonstrated that TNF alpha simultaneously produced insulin resistance by uncoupling insulin receptor activity toward insulin receptor substrate 1 ( IRS 1 ) and suppressing insulin sensitive glucose transport . ^^^ Moreover , when the adipocytes were incubated with exogenous GM 3 , suppression of tyrosine phosphorylation of insulin receptor and IRS 1 and glucose uptake in response to insulin stimulation was observed , demonstrating that GM 3 itself is able to mimic the effects of TNF on insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Also , western blot analysis of insulin like growth factor binding protein 1 was carried out , and further examination was performed of insulin like growth factor 1 signal transduction through tyrosine phosphorylation of insulin receptor substrate 1 , which is a signal transducer of insulin like growth factor 1 . ^^^ Consistent with the results of proteoglycan synthesis , the expression of phosphorylated insulin receptor substrate 1 decreased with age . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regulation of Id 2 gene expression by the type 1 IGF receptor and the insulin receptor substrate 1 . ^^^ These three pathways originate from the tyrosine residue at 950 , a domain in the C terminus , and the activation of the insulin receptor substrate 1 ( IRS 1 ) by the receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The levels of insulin stimulated tyrosine phosphorylation of the insulin receptor beta subunit , insulin receptor substrate ( IRS ) 2 , and p 52 ( Shc ) were increased in diabetic compared with control heart , whereas tyrosine phosphorylation of IRS 1 was unchanged . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vivo insulin infusion increased skeletal muscle insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation ( P = 0 . 01 ) and phosphatidylinositide 3 kinase ( PI 3 kinase ) activity ( phosphotyrosine and IRS 1 associated ) in control subjects ( P < 0 . 02 ) but not in IGT relatives ( NS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Exposure of these cells to ghrelin caused up regulation of several insulin induced activities including tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , association of the adapter molecule growth factor receptor bound protein 2 with IRS 1 , mitogen activated protein kinase activity , and cell proliferation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Western blot analysis revealed no significant differences in the amount of insulin receptor ( IR ) , insulin receptor substrates 1 and 2 ( IRS 1 , IRS 2 ) , and the p 85 subunit of phosphatidylinositol ( PI ) 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Active Rho kinase ( ROK alpha ) associates with insulin receptor substrate 1 and inhibits insulin signaling in vascular smooth muscle cells . ^^^ In control VSMCs , insulin inactivates ROK alpha , the major Rho kinase isoform in VSMCs , and inhibits thrombin induced increase in ROK alpha association with the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , the estrogen receptor ( ER ) content remained similar in tumors from both groups , at least at the protein level , and so did the expression of IGF 1 , IGF 2 , insulin receptor substrate 1 ( IRS 1 ) , IRS 2 and epidermal growth factor receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Absence of insulin receptor substrate 1 expression does not alter GLUT 1 or GLUT 4 abundance or contraction stimulated glucose uptake by mouse skeletal muscle . ^^^ The purpose of this study was to determine the influence of insulin receptor substrate 1 ( IRS 1 ) expression on GLUT 1 and GLUT 4 glucose transporter protein abundance , contraction stimulated glucose uptake , and contraction induced glycogen depletion by skeletal muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , we show that redistribution of PI 3 kinase to the insulin receptor increases insulin stimulated IRS 1 serine phosphorylation , impairs IRS 1 expression and its tyrosine phosphorylation , and decreases the ability of IRS 1 to bind and activate PI 3 kinase in response to insulin . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
The mutation of insulin receptor substrate 1 gene in Chinese patients with non insulin dependent diabetes mellitus . ^^^ OBJECTIVE : To identify the relationship between mutation in the insulin receptor substrate 1 ( IRS 1 ) gene and the incidence of non insulin dependent diabetes mellitus ( NIDDM ) in the Chinese population . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Similar to TNF , cycloheximide and anisomycin stimulated serine phosphorylation of IRS 1 and IRS 2 , reduced their ability to interact with the insulin receptor , inhibited the insulin induced tyrosine phosphorylation of IRS proteins , and diminished their association with phosphatidylinositol 3 kinase ( PI3K ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This phosphorylation was not dependent on insulin receptor or insulin receptor substrate 1 ( IRS 1 ) overexpression and did not occur for the closely related phosphatase SHP 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Heterozygous disruption of Pik3r1 improves insulin signaling and glucose homeostasis in normal mice and mice made insulin resistant by heterozygous deletion of the Insulin receptor and / or insulin receptor substrate 1 ( IRS 1 ) genes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Upon phosphorylation , the C terminal cytoplasmic domain of the beta ( 2 ) adrenergic receptor demonstrates a potent inhibitory feedback action that can block both insulin stimulated autophosphorylation of the insulin receptor and phosphorylation of IRS 1 , 2 in NIH mouse 3T3 L 1 adipocyte membranes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , we demonstrated that PMA inhibited the insulin induced tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Changes observed in IGF 1 signaling components correlated with the activation state of the signal transducing protein insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The amounts of insulin receptor substrate 1 and 2 ( IRS 1 and 2 ) and insulin stimulated phosphorylation of IRSs were also smaller in the transgenic rat . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No differences were found in tyrosine phosphorylation of the insulin receptor , insulin receptor substrate 1 , and phosphatidylinositol 3 kinase among the groups . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A common mutation of the insulin receptor substrate 1 gene is a risk factor for coronary artery disease . ^^^ Insulin receptor substrate 1 ( IRS 1 ) plays a key role in tissue insulin sensitivity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , exercise training did not increase insulin receptor or insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , phosphatidylinositol 3 kinase ( PI 3 kinase ) activity associated with IRS 1 or tyrosine phosphorylated immunoprecipitates , or Akt serine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The protein expression of insulin receptor substrate 1 and protein tyrosine phosphatase with two src homology 2 in the adipose tissue from type 2 diabetic patients ] . ^^^ OBJECTIVE : To investigate the protein expression of insulin receptor substrate 1 ( IRS 1 ) , protein tyrosine phosphatase with two src homology 2 ( SH PTP ( 2 ) ) in adipose tissues of type 2 diabetic patients , and explore molecular mechanisms of insulin resistance from adipose tissues of type 2 diabetic individuals . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation Western blotting experiments showed that phosphorylation levels of IL 4Ralpha , Janus kinase 1 , insulin receptor substrate 1 , and insulin receptor substrate 2 , factors with molecular mass close to the observed 130 kDa major phosphorylation band , increased in response to the combined CD 40 ligation and IL 4 action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular mechanism of insulin induced degradation of insulin receptor substrate 1 . ^^^ Insulin receptor substrate 1 ( IRS 1 ) plays an important role in the insulin signaling cascade . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also showed that normal glucose tolerant carriers of the Gly972Arg polymorphism in the insulin receptor substrate 1 have significantly reduced insulin secretion in response to glucose and arginine but not to GLP 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Thus , insulin receptor substrate 1 and 2 gene expressions were downregulated during acute lipotoxicity , while insulin receptor gene expression was suppressed in chronic lipotoxicity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Incubation with bp 1 01 also enhanced IGF 1 stimulated tyrosine phosphorylation of the IGF I / insulin hybrid receptor and insulin receptor substrate 1 . ^^^ The addition of bp 1 01 ( 200 nm ) plus insulin to HepG 2 cell culture medium resulted in increased tyrosine phosphorylation of the hybrid receptor , insulin receptor substrate 1 , and the glycogen synthesis response compared with the effects of insulin alone . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both p85alpha ( Ile / Asp ) and p85alpha ( Ile / Asn ) also exhibited increased binding to phospho insulin receptor substrate 1 by 41 % and 83 % , respectively ( P < 0 . 001 ) , as compared with p85alpha ( Met / Asp ) . ^^^ The expression of p85alpha ( Ile ) was also slightly decreased and the binding to insulin receptor substrate 1 slightly increased in brown preadipocytes derived from p85alpha knockout mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Upon insulin stimulation , tyrosine phosphorylation of ( insulin receptor substrate 1 ) IRS 1 was much higher in IGF IR ( / ) brown adipocytes , although IRS 1 protein content was reduced . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Gly972Arg polymorphism in insulin receptor substrate 1 is associated with decreased birth weight in a population based sample of Brazilian newborns . ^^^ OBJECTIVE : We studied the association between the Gly972Arg polymorphism in insulin receptor substrate 1 ( IRS 1 ) and birth weight in a population based sample of Brazilian newborns . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The appearance of a complex between tyrosine phosphorylated insulin receptor substrate 1 ( IRS 1 ) and PI3K in a high speed pellet fraction ( HSP ) is thought to be a key event in insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Effect of treatment with different doses of 17 beta estradiol on insulin receptor substrate 1 . ^^^ CONCLUSIONS : Our results suggest that low concentrations of 17 beta estradiol could be responsible for the upregulation of insulin receptor substrate 1 , increasing insulin sensitivity in muscle and adipose tissue . ^^^ However , insulin receptor substrate 1 is downregulated with high concentrations of 17 beta estradiol , thus these high hormone plasma levels could favour insulin resistance in peripheral tissues . ^^^ The role of 17 beta estradiol seems to modulate insulin receptor substrate 1 levels in insulin dependent tissues , but in a different manner in each tissue . ^^^ OBJECTIVE : We tried to determine whether different doses of 17 beta estradiol cause changes in the regulation of insulin receptor substrate ( IRS 1 ) levels , and if so , the possible implications in insulin sensitivity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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: P06213 and P35568 Pubmed SVM Score :0.0
Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate 1 , phosphatidylinositol 3 kinase and protein kinase B in primary cultured rat adipocytes . ^^^ After the culture period , the cells were washed and then basal and insulin stimulated glucose uptake , insulin binding and lipolysis as well as cellular content of insulin signalling proteins ( insulin receptor substrate 1 ( IRS 1 ) , IRS 2 , phosphatidylinositol 3 kinase ( PI 3 K ) and protein kinase B ( PKB ) ) and glucose transporter isoform GLUT 4 were measured . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Treatment with 17 AAG decreased NPM ALK expression and phosphorylation , thus impairing its association with phospholipase C gamma , Src homology 2 domain containing protein ( Shc ) , growth factor receptor bound protein 2 ( Grb 2 ) , and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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: P06213 and P35568 Pubmed SVM Score :0.0
Focusing our studies in day 2 ( hyperglycaemia / hyperinsulinaemia ) and day 5 ( normoglycaemia / hyperinsulinaemia ) we found , particularly in day 5 , that the early steps of the insulin signalling cascade in skeletal muscle of glucose infused rats were not more activated when compared to control animals as assessed by a comparable phosphorylation of the insulin receptor , IRS 1 and PKB and by an unaltered IRS 1 associated Ptd ( Ins ) 3 ' kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 associated PI 3 kinase activation and insulin receptor autophosphorylation were comparable in the two groups . ^^^ Protein expression levels for the insulin receptor , IRS 1 , IRS 2 , the p 85 regulatory subunit of PI 3 kinase , Akt , PKC zeta / lambda , GLUT 1 , and GLUT 4 were also similar in the two groups . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated phosphorylation of insulin receptor substrate ( IRS ) 1 and IRS 2 was increased by 61 and 72 % respectively , while IRS 1 and IRS 2 protein levels were increased by 76 and 95 % . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Direct measurement of phosphotyrosine phosphatase activity and reconstitution experiments using tyrosine phosphorylated insulin receptor substrate 1 ( IRS 1 ) indicated that IGFBP 3 activated a phosphotyrosine phosphatase ( PTPase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PUGNAc induced insulin resistance was associated with increased O GlcNAc modification of several proteins including insulin receptor substrate 1 and beta catenin , two important effectors of insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Candidate genes for the metabolic syndrome include those for the beta 3 adrenergic receptor , lipoprotein lipase , hormone sensitive lipase , peroxisome proliferator activated receptor gamma , insulin receptor substrate 1 and glycogen synthase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation and immunoblotting were used to detect insulin mediated tyrosine phosphorylation of both IR beta and insulin receptor substrate ( IRS ) 1 , and insulin stimulated binding of IRS 1 to p 85 regulatory subunit of phosphatidylinositol 3 kinase ( PI 3 K ) in the extracted muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nitric oxide regulates oestrogen activated signalling pathways at multiple levels through cyclic GMP dependent recruitment of insulin receptor substrate 1 . ^^^ Exposure of these cells to 17 beta oestradiol ( E ( 2 ) ) in the presence of NO gave rise to activation of signalling events additional to those triggered by E ( 2 ) alone , namely tyrosine phosphorylation of specific proteins , including the insulin receptor substrate 1 , with recruitment to this adapter of the phosphatidylinositol 3 ' kinase and persistent activation of Akt ( protein kinase B ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Correspondingly , 24 h exposure of 3T3 L 1 adipocytes to TNF alpha resulted in reduced protein levels of GLUT 4 and several insulin signaling proteins , including the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , and protein kinase B ( AKT ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recently , the common Gly ( 972 ) > Arg amino acid polymorphism of insulin receptor substrate 1 ( Arg ( 972 ) IRS 1 ) has been associated with human type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
HG culturing also enhanced insulin stimulated insulin receptor and insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylations while decreasing basal phosphorylations . ^^^ Antisense inhibition of SHP 2 reverted the effect of HG on basal and insulin stimulated insulin receptor and IRS 1 phosphorylation as well as that on thymidine incorporation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol 3 kinase activity in muscle . ^^^ Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking insulin activation of insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Recent studies in a human cell line and a mouse model suggest that metastatic prostate cancer cell detachment may be favored by impairing cadherin function via loss of expression of insulin receptor substrate 1 ( IRS 1 ) , the principal IGF1R docking molecule . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Receptors for insulin and insulin like growth factor 1 and insulin receptor substrate 1 mediate pathways that regulate islet function . ^^^ Conventional insulin receptor substrate 1 ( IRS 1 ) knockouts manifest growth retardation and mild insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The mutant was capable of insulin dependent autophosphorylation and phosphorylation of insulin receptor substrate 1 in vivo and could be cross linked into receptor dimers when membrane bound . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Role of the insulin receptor substrate 1 and phosphatidylinositol 3 kinase signaling pathway in insulin induced expression of sterol regulatory element binding protein 1c and glucokinase genes in rat hepatocytes . ^^^ Overexpression of an NH ( 2 ) terminal fragment of IRS 1 that contains the pleckstrin homology and phosphotyrosine binding domains ( insulin receptor substrate 1 NH ( 2 ) terminal fragment [ IRS 1N ] ) inhibited insulin induced tyrosine phosphorylation of IRS 1 as well as the association of IRS 1 with phosphatidylinositol ( PI ) 3 kinase activity , whereas the tyrosine phosphorylation of IRS 2 and its association with PI 3 kinase activity were slightly enhanced . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
TNF alpha , given 5 min before insulin , inhibited insulin induced tyrosine phosphorylation of insulin receptor ( IR ) , IR substrate ( IRS ) 1 , insulin induced association of IRS 1 with the p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 K ) , and insulin induced glucose uptake . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Positive and negative regulatory role of insulin receptor substrate 1 and 2 ( IRS 1 and IRS 2 ) serine / threonine phosphorylation . ^^^ To determine whether basal Ser / Thr phosphorylation of IRS proteins influences insulin receptor catalyzed tyrosine phosphorylation , recombinant FLAG epitope tagged IRS 1 ( F IRS 1 ) and IRS 2 ( F IRS 2 ) were expressed , purified , and subjected to both dephosphorylation and hyperphosphorylation prior to phosphorylation by the insulin receptor kinase . ^^^ As expected , hyperphosphorylation of F IRS 1 and F IRS 2 by GSK3beta decreased their subsequent phosphorylation on tyrosine residues by the insulin receptor . ^^^ Surprisingly , however , dephosphorylation of the basal Ser / Thr phosphorylation sites impaired subsequent phosphorylation on tyrosine , suggesting that basal Ser / Thr phosphorylation of F IRS 1 and F IRS 2 plays a positive role in phosphorylation by the insulin receptor tyrosine kinase . ^^^ IRS 1 and IRS 2 from serum fed cells were hyperphosphorylated , and dephosphorylation induced either by serum deprivation or by alkaline phosphatase treatment after immunoprecipitation led to an increase in tyrosine phosphorylation by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
MECHANISMS : Clinical and experimental evidence suggests that the higher breast cancer risk associated with greater abdominal visceral obesity may be related to aberrant insulin signalling through the insulin receptor substrate 1 pathway , leading to insulin resistance , hyperinsulinaemia and increased concentrations of endogenous oestrogen and androgen . ^^^ Aetiological factors in the development of hyperinsulinaemic insulin resistance are still uncertain but may involve aberrant susceptibility genes in adipocyte insulin receptors or in the insulin receptor substrate 1 pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Rosiglitazone ameliorated the defect in hepatocyte insulin stimulated tyrosine phosphorylation of the insulin receptor , IRS 1 , and IRS 2 and the reduced protein mass of IRS 1 and IRS 2 induced by fructose feeding . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Troglitazone abolished Ang 2 induced suppression of phosphatidilinositol 3 kinase ( PI 3 kinase ) activity , insulin receptor substrate 1 ( IRS 1 ) associated tyrosine phosphorylation , and IRS 1 associated p 85 levels in VSMC from WKY rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Overexpression of insulin receptor substrate 1 , but not insulin receptor substrate 2 , protects a T cell hybridoma from activation induced cell death . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this model , IGF 1 did not activate the focal adhesion kinase , whereas it induced tyrosine phosphorylation of the insulin receptor substrate 1 and activation of the extracellular signal related kinase 1 and 2 , p 38 , phosphatidylinositol 3 ' kinase and protein kinase B / Akt . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
Nuclear translocation of insulin receptor substrate 1 by the simian virus 40 T antigen and the activated type 1 insulin like growth factor receptor . 32D cells are a murine hemopoietic cell line that undergoes apoptosis upon withdrawal of interleukin 3 ( IL 3 ) from the medium . 32D cells have low levels of the type 1 insulin like growth factor ( IGF 1 ) receptor and do not express insulin receptor substrate 1 ( IRS 1 ) or IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In response to IGF 1 treatment , the expression of kinases in the c Jun / c Jun NH ( 2 ) terminal kinase signaling pathway ( MEKK 1 , MEK 4 , and JNK1 / 2 ) was unchanged , but expressions of insulin receptor substrate 1 and Grb 2 associated binder 1 ( Gab 1 ) were significantly decreased . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Stimulation with CGP 12177 did not impair insulin receptor kinase activity but decreased insulin receptor substrate 1 binding to phosphatidylinositol ( PI ) 3 kinase and activation of protein kinase B . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The KO mice exhibited severe diet induced insulin resistance with reduced insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol 3 kinase ( PI 3 kinase ) activity in muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signaling in human skeletal muscle is activated by physiological insulin concentrations , but the increase in insulin action after exercise does not seem to be related to increased insulin signaling [ insulin receptor tyrosine kinase activity , insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation ( RS 1 ) , IRS 1 associated phosphatidylinositol 3 kinase activity , Akt phosphorylation ( Ser ( 473 ) ) , glycogen synthase kinase 3 ( GSK 3 ) phosphorylation ( Ser ( 21 ) ) , and GSK3alpha activity ] , as measured in muscle lysates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation , phosphatidylinositol 3 kinase activation , and Akt phosphorylation also diminished , as did insulin mediated glucose uptake . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After receptor binding , growth hormone ( GH ) induces GH receptors ( GHR ) dimerization and JAK 2 is activated after its association with a dimerized GHR , stimulating the tyrosyl phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , IRS 2 and Shc proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Deficient expression of insulin receptor substrate 1 ( IRS 1 ) fails to block insulin like growth factor 1 ( IGF 1 ) stimulation of brain growth and myelination . ^^^ To determine whether insulin receptor substrate 1 ( IRS 1 ) is essential in mediating insulin like growth factor 1 ( IGF 1 ) stimulation of brain growth and myelination in vivo , we cross bred IGF 1 transgenic ( Tg ) mice with IRS 1 null mutant ( IRS 1 ( / ) ) mice and examined brain growth and expression of myelin specific proteins in mice that overexpress IGF 1 with or without IRS 1 expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A majority of these complex and interrelated pathways appear to converge at the level of insulin receptor substrate 1 by promoting its serine phosphorylation in order to mediate heterologous inhibition of insulin receptor substrate 1 signaling which , in turn , counterregulates the insulin response . ^^^ Other possible mechanisms of insulin resistance in cytokine treated cells include nitration of insulin receptor substrate 1 tyrosine residues by nitric oxide derived reactive nitrogen species as well as direct interference with insulin signaling molecules further downstream such as protein kinase B / Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Lactate infusion did not alter insulin ' s ability to phosphorylate the insulin receptor , the insulin receptor substrate ( IRS ) 1 , or IRS 2 but decreased insulin ' s ability to stimulate IRS 1 and IRS 2 associated phosphatidylinositol 3 kinase activities and Akt / protein kinase B activity by 47 , 75 , and 55 % , respectively ( P < 0 . 05 for all ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
RESULTS : In rat muscle , increases in tyrosine phosphorylation of insulin receptor ( IR ) and activity of the insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol ( PI ) 3 kinase activity by insulin were similar or higher in freeze dried and purified muscle than wet muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS AND RESULTS : Treatment of primary aortic smooth muscle cells from newborn rats with the NO donor S nitroso N acetylpenicillamine reduced cell motility , tyrosine phosphorylation levels of insulin receptor beta subunit and insulin receptor substrate 1 , and extracellular signal regulated kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , like insulin , EGCG increases tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) , and it reduces phosphoenolpyruvate carboxykinase gene expression in a phosphoinositide 3 kinase dependent manner . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interaction effect between common polymorphisms in PPARgamma 2 ( Pro12Ala ) and insulin receptor substrate 1 ( Gly972Arg ) on insulin sensitivity . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^ Consistent with this suggestion , IGF 1 induced phosphorylation of extracellular signal regulated kinase , AKT , and insulin receptor substrate 1 was unaffected by ICI treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This training induced enhancement of insulin action is associated with upregulation of specific components of the glucose transport system in insulin resistant muscle and includes increased protein expression of GLUT 4 and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 was completely blocked , with unaltered expression of IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The increase in Akt pT 308 was correlated with an increase in Akt phosphorylation at serine 473 ( Akt pS 473 ) , tyrosine phosphorylation of insulin receptor beta subunit and insulin receptor substrate 1 , and serine phosphorylation of glycogen synthase kinase 3alpha / beta . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 and phosphoinositide dependent kinase 1 are required for insulin stimulated production of nitric oxide in endothelial cells . ^^^ In this study , we evaluated roles of insulin receptor substrate 1 ( IRS 1 ) and phosphoinositide dependent kinase 1 ( PDK 1 ) in production of NO . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulates tyrosine kinase activity of its receptor , resulting in phosphorylation of its cytosolic substrate , insulin receptor substrate 1 , which , in turn , associates with proteins containing SH 2 domains , including phosphatidylinositol 3 kinase ( PI 3 kinase ) and the phosphotyrosine phosphatase SHP 2 . ^^^ The regulation of these associations in situations of altered insulin receptor substrate 1 ( IRS 1 ) phosphorylation was not yet investigated . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It is hypothesized that FFAs interfere with insulin signaling via protein kinase C induced serine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
TNF alpha results in insulin insensitivity , indirectly by stimulating stress hormone production and directly by sustained induction of SOCS 3 which decreases insulin induced insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation and its association with the p 85 , regulatory subunit of phosphatidylinositol 3 kinase ; and by negative regulation of PPAR gamma . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also observed that the major IGFRI substrate , insulin receptor substrate 1 ( IRS 1 ) , was constitutively tyrosine phosphorylated and could be co immunoprecipitated with EN in either R or R+ cells expressing the EN oncoprotein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) gene polymorphisms have been identified in type 2 diabetic patients ; however , it is unclear how such polymorphisms contribute to the development of diabetes . ^^^ The expression of insulin receptor and IRS 1 and IRS 2 was decreased in obese IRS 1 ( + / ) , which could in part explain the profound insulin resistance in these mice . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^ These data also highlight growth factor receptor adaptor molecules , such as insulin receptor substrate 1 , rather than the receptors themselves as targets for antitumor therapeutic strategies . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The C / EBPbeta / delta deficient adipocytes also expressed lower amounts of insulin receptor substrate 2 ( IRS 2 ) than the adipocytes derived from wild type MEFs , whereas the amounts of insulin receptor and IRS 1 were similar . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the biopsies , insulin receptor kinase ( IRK ) activity , insulin receptor substrate ( IRS ) 1 associated phosphatidylinositol 3 kinase ( PI3K ) activity , Ser ( 473 ) and Thr ( 308 ) phosphorylation of protein kinase B ( PKB ) , and protein expression of IRS 1 , IRS 2 , phosphoinositol dependent kinase 1 ( PDK 1 ) , PKB , and GLUT 4 were determined . ^^^ Troglitazone did not alter insulin receptor number or IRS 1 , IRS 2 , PKB , PDK 1 , or GLUT 4 protein expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nuclear translocation of insulin receptor substrate 1 by oncogenes and Igf 1 . ^^^ The insulin receptor substrate 1 ( IRS 1 ) is one of the major substrates of both the insulin and IGF 1 receptors and is generally localized in the cytosol / membrane fraction of the cell . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) ( / ) mice are lean with a reduced fat cell size and have insulin resistance due to a primary defect of insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Relationship of insulin receptor substrate 1 and 2 genotypes to phenotypic features of polycystic ovary syndrome . ^^^ Polymorphisms in the genes encoding the insulin receptor substrate ( IRS ) proteins , IRS 1 ( Gly ( 972 ) Arg ) and IRS 2 ( Gly ( 1057 ) Asp ) , influence susceptibility to type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , we observed that translocation of GLUT 4 to the plasma membrane was significantly enhanced by temocapril treatment without influencing insulin receptor substrate 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Dexamethasone did not alter insulin binding , insulin receptor number or kinase activity , insulin receptor substrate 1 and Akt protein expression / phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we show that stimulation by insulin of freshly isolated primary adipocytes resulted in the expected rapid tyrosine phosphorylation of the insulin receptor , IRS 1 and IRS 3 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These alterations in glucose transport activity are likely the result of dysregulation of intramyocellular fatty acid metabolism , whereby fatty acids cause insulin resistance by activation of a serine kinase cascade , leading to decreased insulin stimulated insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation and decreased IRS 1 associated phosphatidylinositol 3 kinase activity , a required step in insulin stimulated glucose transport into muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated tyrosine phosphorylation of insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) was determined . 3 Chronic insulin treatment resulted in 60 and 40 % reduction in insulin stimulated tyrosine phosphorylation of IR and IRS 1 , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Down regulation of cell surface insulin receptor and insulin receptor substrate 1 phosphorylation by inhibitor of 90 kDa heat shock protein family : endoplasmic reticulum retention of monomeric insulin receptor precursor with calnexin in adrenal chromaffin cells . ^^^ In GA treated cells , insulin induced tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was attenuated by 77 % , with no change in IRS 1 level . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The pleckstrin homology ( PH ) domain interacting protein couples the insulin receptor substrate 1 PH domain to insulin signaling pathways leading to mitogenesis and GLUT 4 translocation . ^^^ Receptor mediated tyrosine phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) is required for the propagation of many of insulin ' s biological effects . ^^^ The amino terminal pleckstrin homology ( PH ) domain of IRS 1 plays a pivotal role in promoting insulin receptor ( IR ) IRS 1 protein interactions . ^^^ Our results are consistent with the hypothesis that PHIP represents a physiological protein ligand of the IRS 1 PH domain , which plays an important role in insulin receptor mediated mitogenic and metabolic signal transduction . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex . ^^^ One mechanism mediating insulin resistance may involve the phosphorylation of serine residues in insulin receptor substrate 1 ( IRS 1 ) , leading to impairment in the ability of IRS 1 to activate downstream phosphatidylinositol 3 kinase dependent pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This effect occurred through a highly significant reduction in phosphatidylinositol 3 kinase / Akt pathway activation ( 80 % reduction in phosphatidylinositol 3 kinase activity , 55 % inhibition of Akt activation ) accompanied by a 65 % decrease in insulin receptor substrate 1 growth factor induced tyrosine phosphorylation . ^^^ These results provide the first evidence that PTPL1 / FAP 1 has a key role in the apoptotic process in human breast cancer cells independent of Fas but associated with an early inhibition of the insulin receptor substrate 1 / phosphatidylinositol 3 kinase pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Genetic variants of insulin receptor substrate 1 ( IRS 1 ) in syndromes of severe insulin resistance . ^^^ RESULTS : Chinese hamster ovary ( CHO ) cells stably over expressing the insulin receptor were transiently transfected with vectors expressing either wild type , Glu 1158 or Pro 513 IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
ERbeta expression was up regulated and the levels of insulin receptor substrate 1 ( IRS 1 ) remained low throughout all phases . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Common variants in the lipoprotein lipase gene , but not those in the insulin receptor substrate 1 , the beta 3 adrenergic receptor , and the intestinal fatty acid binding protein 2 genes , influence the lipid phenotypic expression in familial combined hyperlipidemia . ^^^ Therefore , we have evaluated the association of the common variants in the lipoprotein lipase ( LPL ) ( D9N , N291S , and S447X ) , insulin receptor substrate 1 ( IRS 1 ) ( G972R ) , fatty acid binding protein 2 ( FABP 2 ) ( A54T ) , and beta 3 adrenergic receptor ( beta 3 AR ) ( W64R ) genes with lipid and lipoprotein levels in 30 Italian FCHL families ( 195 individuals ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A novel mechanistic model of postreceptor events including phosphorylation of insulin receptor substrate 1 , activation of phosphatidylinositol 3 kinase , and subsequent activation of downstream kinases Akt and protein kinase C zeta is coupled with previously validated subsystem models of insulin receptor binding , receptor recycling , and GLUT 4 translocation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced insulin receptor substrate 1 tyrosine phosphorylation and binding to the regulatory subunit p 85 of phosphatidylinositol 3 kinase ( PI 3 kinase ) were diminished by approximately 60 % and 40 % , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrates ( IRS 1 and IRS 2 ) are essential for intracellular signaling by insulin and insulin like growth factor 1 ( IGF 1 ) , anabolic regulators of bone metabolism . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We recently demonstrated that epinephrine could inhibit the activation by insulin of insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol 3 kinase ( PI 3 kinase ) in skeletal muscle ( Hunt DG , Zhenping D , and Ivy JL . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The fact that the function of two key targets of insulin action , glycogen synthase and insulin receptor substrate 1 , are suppressed by GSK 3 , as well as the fact that GSK 3 activity is higher in diabetic tissues , makes it a promising drug discovery target for insulin resistance and Type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After treatments with cariporide or bafilomycin A 1 , insulin stimulation of insulin receptor and insulin receptor substrate 1 phosphorylation and Akt activity were normal . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein tyrosine phosphatase 1B ( PTP1B ) is a negative regulator of the tyrosine phosphorylation of the insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this brief review , we focused on insulin receptor substrate 1 ( IRS 1 ) in skeletal muscle cells , and the significance of its serine ( 612 ) phosphorylation was discussed . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 is present in hepatocyte nuclei from intact rats . ^^^ Insulin receptor substrate 1 ( IRS 1 ) , the primary substrate for the insulin receptor tyrosine kinase in most cells and tissues , is a key component of the insulin signaling network . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Salicylic acid reverses phorbol 12 myristate 13 acetate ( PMA ) and tumor necrosis factor alpha ( TNFalpha ) induced insulin receptor substrate 1 ( IRS 1 ) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 ( HEK 293 ) cells . ^^^ Protein kinase C isoforms and tumor necrosis factor alpha ( TNFalpha ) signaling pathways are well described mediators of insulin resistance ; they are implicated in the activation of IKKbeta and the subsequent inhibition of proximal insulin signaling via insulin receptor substrate 1 ( IRS 1 ) and Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although insulin receptor substrate 1 tyrosine phosphorylation was unaffected by gliclazide treatment , phosphatidylinositol 3 kinase activity was partially restored by treatment with gliclazide . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we report that SP A treatment leads to rapid tyrosine specific phosphorylation of several important proteins in lung epithelial cells including insulin receptor substrate 1 ( IRS 1 ) , an upstream activator of PI3K . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumors : therapeutic implications . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a major substrate of insulin , insulin like growth factors , and cytokine signaling and plays an important role in mediating apoptosis , cell differentiation , and cell transformation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activation of the c Jun N terminal kinase ( JNK ) by proinflammatory cytokines inhibits insulin signaling , at least in part , by stimulating phosphorylation of rat / mouse insulin receptor substrate 1 ( Irs 1 ) at Ser ( 307 ) ( Ser ( 312 ) in human IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
In the present experiments we demonstrate that higher insulin receptor and insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) concentrations are predominantly encountered in cells of the periphery of rat pancreatic islets , as compared to centrally located cells , and that partial blockade of IRS 1 protein expression by antisense oligonucleotide treatment leads to improved insulin secretion induced by glucose overload , which is accompanied by lower steady state glucagon secretion and blunted glucose induced glucagon fall . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Even though the decrease in insulin receptor substrate protein 1 ( IRS 1 ) phosphorylation was identical with that seen in L 6 myocytes , overexpression of wild type PTP1B in L 1 adipocytes was associated with modest impairment of insulin stimulated Akt phosphorylation in addition to a small , but significant , attenuation in insulin stimulated glucose uptake , when compared with a phosphatase negative mutant . ^^^ Regarding the relatively small effect on Akt phosphorylation , we obtained identical results in rat 1 fibroblasts overexpressing human insulin receptor , suggesting that the higher expression levels of insulin receptor and IRS 1 might be responsible . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Previous work suggests that ERK activation in response to GH may be modulated by several proteins acting as docking molecules , including the epidermal growth factor receptor ( EGFR ) and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Short term denervation induced a significant fall in glucose clearance rates ( 62 % of control , P < 0 . 05 ) as detected by euglycemic hyperinsulinemic clamp and was associated with a significant decrease in insulin stimulated tyrosine phosphorylation of the insulin receptor ( IR ; 73 % of control , P < 0 . 05 ) , IR substrate 1 ( IRS 1 ; 69 % of control , P < 0 . 05 ) , and IRS 2 ( 82 % of control , P < 0 . 05 ) and serine phosphorylation of Akt ( 39 % of control , P < 0 . 05 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Because insulin receptor substrate 1 also associates with 14 3 3 , the dimeric 14 3 3 beta could function as a scaffolding protein in the activation of PDE3B by insulin . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IGF binding protein 5 , IGF 2 , and insulin receptor substrate 1 all displayed altered patterns and levels of expression in C / EBPbeta ( null ) mice , suggestive of a change in the IGF signaling axis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Stat5b and insulin receptor substrate 1 ( IRS 1 ) interact with the same autophosphorylation site in the IR [ phosphotyrosine ( pY ) 972 ] in yeast two hybrid assays , and the IR phosphorylates Stat5b in vitro . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate 1 expression . ^^^ Interestingly , the expression of insulin receptor substrate 1 ( IRS 1 ) was diminished in MEKK 1 deficient fibroblasts , which is similar to an earlier finding in FAK deficient fibroblasts . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In two cohorts of 174 and 165 obese Caucasian children , we measured insulin sensitivity and genotyped insulin receptor substrate IRS 1 and IRS 2 genes for the Arg972Gly and the Asp1057Gly variants , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Studies with transgenic models have shown that the beta cell selective insulin receptor knockout and the IRS 1 knockout lead to reduced glucose induced insulin secretion . ^^^ Overexpression of the insulin receptor and IRS 1 in beta cells results in increased insulin secretion and increased cytosolic Ca ( 2+ ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased frequency of the G972R variant of the insulin receptor substrate 1 ( irs 1 ) gene among girls with a history of precocious pubarche . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Microgravity completely suppressed the mRNA expression of the insulin receptor substrate 1 , the postreceptor signaling molecule of IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
Grb 10 inhibits insulin stimulated insulin receptor substrate ( IRS ) phosphatidylinositol 3 kinase / Akt signaling pathway by disrupting the association of IRS 1 / IRS 2 with the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Based on the phenotypes of knockout mice and cell lines , as well as pathway specific analysis , the insulin receptor substrates IRS 1 , IRS 2 , IRS 3 , and IRS 4 have been shown to play unique roles in insulin signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To examine the roles of these IRS in apoptosis inhibition , we evaluated staurosporine induced apoptosis in Chinese hamster ovary ( CHO ) cells overexpressing human insulin receptor and IRS 1 or IRS 3 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Modulation of insulin stimulated degradation of human insulin receptor substrate 1 by Serine 312 phosphorylation . ^^^ Ser / Thr phosphorylation of insulin receptor substrate 1 ( IRS 1 ) is a negative regulator of insulin signaling . ^^^ One potential mechanism for this is that Ser / Thr phosphorylation decreases the ability of IRS 1 to be tyrosine phosphorylated by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
During differentiation with ritonavir ( i . e . , 1 11 days post addition of differentiating cocktail ) , insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation was ascertained ( day 11 ) and found to be decreased in the ritonavir exposed cells when compared with control cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 regulation of sarco endoplasmic reticulum calcium ATPase 3 in insulin secreting beta cells . ^^^ We have previously characterized an insulin receptor substrate 1 ( IRS 1 ) overexpressing beta cell line . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We investigated the effect of ceramide on insulin signaling pathways , such as insulin receptor ( IR ) beta subunit , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 kinase ( PI3K ) , and protein kinase Czeta ( PKCzeta ) in rat adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced up regulated uncoupling protein 1 expression is mediated by insulin receptor substrate 1 through the phosphatidylinositol 3 kinase / Akt signaling pathway in fetal brown adipocytes . ^^^ To investigate the role of insulin receptor substrate 1 ( IRS 1 ) and its downstream signaling in insulin induced thermogenic differentiation of brown adipocytes , we have reconstituted IRS 1 deficient fetal brown adipocytes ( IRS 1 ( / ) ) with wild type IRS 1 ( IRS 1 ( wt ) ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Hyperosmolarity induces sustained suppression of p70S6 kinase and 4E BP 1 hyperphosphorylation by insulin , whereas insulin induced tyrosine phosphorylation of the insulin receptor ( IR ) beta subunit and the IR substrates IRS 1 and IRS 2 , recruitment of the phosphoinositide 3 kinase ( PI 3 kinase ) regulatory subunit p 85 to the receptor substrates as well as PI 3 kinase activation , and Ser 473 phosphorylation of protein kinase B and Thr 410 / 403 phosphorylation of PKC zeta / lambda are largely unaffected under hyperosmotic conditions . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
High glucose and insulin in combination cause insulin receptor substrate 1 and 2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes : possible implications for insulin resistance in type 2 diabetes . ^^^ At high glucose , insulin receptor substrate 1 ( IRS 1 ) expression was downregulated by approximately 20 50 % , whereas IRS 2 was strongly upregulated by glucose levels of 10 mmol / l or more ( by 100 400 % ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Study on base insertion / deletion of CAG rich region in insulin receptor substrate 1 5 ' regulatory sequence ] . ^^^ To study the relationship of the polymorphism of the insulin receptor substrate 1 ( IRS 1 ) gene 5 ' flanking regulatory sequence and Type 2 diabetes , the IRS 1 gene 5 ' flanking regulatory sequence was scanned by PCR SSCP in 78 healthy control subjects and 76 Type 2 diabetic subjects . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IGF IR ( / ) cells showed an increased insulin sensitivity regarding insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation despite a substantial reduction in IRS 1 protein content . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Upon JAK 2 activation , tyrosine phosphorylation of signal transducer and activator of transcription 1 ( STAT 1 ) , STAT 5b , insulin receptor substrate 1 ( IRS 1 ) , and Src homology and collagen homology ( Shc ) were detected . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here , we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS 1 and 2 , increases binding of activated IRS 1 and 2 to the regulatory subunit of PI3K , and activates protein kinase B / Akt , a downstream target of PI3K . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The MEK 1 mutant , which activates ERK , markedly down regulated expression of the insulin receptor ( IR ) and its major substrates , IRS 1 and IRS 2 , mRNA and protein , and in turn reduced tyrosine phosphorylation of IR as well as IRS 1 and IRS 2 and their associated phosphatidyl inositol 3 kinase ( PI3K ) activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Finally , induction of insulin receptor substrate ( IRS ) 1 in the mammary glands of PRL treated mice and induction of IRS 1 and IRS 2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF I / insulin receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inhibitory effect of JNK appears to be mediated by serine phosphorylation of IRS 1 ( insulin receptor substrate ) since both Taxol and IGF 1 treatment enhanced Ser ( 312 ) IRS 1 phosphorylation , while LY 294002 blocked IGF 1 mediated phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This study aimed to examine the effects of insulin on glucose transport and changes in insulin receptor tyrosine phosphorylation , IRS 1 and PC 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study we used K 562 cells to demonstrate that insulin receptor substrate 1 ( IRS 1 ) is expressed and constitutively phosphorylated in BCR ABL ( + ) cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ectopically expressed SOCS 3 associated with the IR and suppressed insulin dependent receptor autophosphorylation , insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , association of IRS 1 with the p 85 subunit of phosphatidylinositol 3 kinase , and activation of Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We examined the expression of PGC 1 , PPAR gamma , insulin receptor substrate 1 ( IRS 1 ) , glucose transporter isoform 4 ( GLUT 4 ) , and mitochondrial uncoupling protein 1 ( UCP 1 ) in adipose tissue and skeletal muscle from non obese , non diabetic insulin resistant , and insulin sensitive individuals . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Twenty four h pretreatment of cells with scFv Fc blocked IGF 1 mediated phosphorylation of insulin receptor substrate 1 and subsequent extracellular signal regulated kinase 1 / extracellular signal regulated kinase 2 and phosphatidylinositol 3 ' kinase activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Chronic vanadate exposure was associated with activation of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , PKB / Akt , and p 38 MAPK . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of insulin receptor substrate 1 is detected when enriched by immunoprecipitation with anti PI3K antibody . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Intima media thickness of carotid arteries is reduced in heterozygous carriers of the Gly972Arg variant in the insulin receptor substrate 1 gene . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In summary , ( 1 ) PI3K mediates insulin induced reduction of IRS 1 by phosphorylating it while a PI3K / mTOR pathway controls insulin induced reduction of IRS 2 , ( 2 ) in L 6 cells , IRS 2 is the major adapter molecule linking the insulin receptor to activation of PKB and MAPK , ( 3 ) the mechanism of IRS 1 / 2 down regulation is different in L 6 cells compared with 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Distinct effects of ketone bodies on down regulation of cell surface insulin receptor and insulin receptor substrate 1 phosphorylation in adrenal chromaffin cells . ^^^ Immunoprecipitation followed by immunoblot analysis revealed that insulin induced ( 100 nM for 10 min ) tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) was attenuated by 56 % in acetoacetate treated cells , with no change in IRS 1 level . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Since an altered phosphotyrosine phosphatase activity could represent a mechanism by which insulin signaling is influenced , we also assessed potential indinavir effects on protein tyrosine phosphatase activity directed against tyrosine phosphorylated insulin receptor substrate 1 . ^^^ Dephosphorylation of immobilized tyrosine phosphorylated insulin receptor substrate 1 by the cell extracts was determined using a microwell plate based method , and indinavir treatment did not alter this dephosphorylation . ^^^ Finally , our data do not support the hypothesis that indinavir alters insulin signaling by influencing protein tyrosine phosphatase activity directed against insulin receptor substrate 1 . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Arg ( 972 ) insulin receptor substrate 1 ( IRS 1 ) variant has been hypothesized to play a role in pancreatic beta cell stimulus coupled insulin secretion and survival . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , resistin did not alter the insulin receptor ( IR ) content and its phosphorylation , nor did it affect insulin stimulated insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation , its association with the p 85 subunit of phosphatidylinositol ( PI ) 3 kinase , or IRS 1 associated PI 3 kinase enzymatic activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Adipose specific expression , phosphorylation of Ser 794 in insulin receptor substrate 1 , and activation in diabetic animals of salt inducible kinase 2 . ^^^ Coexpressed with human insulin receptor substrate 1 ( IRS 1 ) in COS cells , SIK 2 could phosphorylate Ser ( 794 ) of human IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Exposure to 100 nM IGF 1 for 10 min resulted in increased insulin receptor substrate 1 associated PI3K activity and Akt kinase activity , whereas 100 nM Ang 2 pretreatment for 5 min strikingly decreased these IGF 1 effects . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of insulin receptor beta subunit ( IRbeta ) and insulin receptor substrate 1 ( IRS 1 ) and tyrosine / threonine phosphorylation of p44 / 42 MAPK ( ERK 1 / 2 ) were evaluated . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have investigated whether different doses of 17beta oestradiol mediate changes in insulin sensitivity and if these changes could be related to modifications of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the course of pregnancy increasing insulin resistance develops due to deteriorated phosphorylation of the insulin receptor and its substrate ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , captopril treatment caused an increase in insulin induced insulin receptor substrate 1 ( IRS 1 ) phosphorylation accompanied by an increased association of IRS 1 with phosphoinositide 3 kinase ( PI 3 kinase ) , despite no change on insulin receptor ( IR ) autophosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate ( IRS ) 1 was associated with PI3K activity , which is necessary for Akt activation by insulin , and was reduced in obese muscles , and this was accompanied by decreased IRS 1 expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Concomitantly , only aged adrenomedullin deficient mice not only showed increased production of muscular reactive oxygen species , as demonstrated by the electron spin resonance method , but also had significantly decreased insulin stimulated glucose uptake into the soleus muscle associated with impairment of insulin signals such as insulin receptor substrate 1 , 2 and phosphatidylinositol 3 kinase activities . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Three hours after estradiol treatment , there was an enhanced immunocoprecipitation of estrogen receptor alpha with p 85 subunit of phosphatidylinositol 3 kinase , as well as an enhanced immunocoprecipitation of p 85 with insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein levels of insulin receptor beta subunit ( IR beta ) , insulin receptor substrate 1 ( IRS 1 ) and p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) were determined in total cell lysates by Western immunoblot . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A novel T608R missense mutation in insulin receptor substrate 1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling . ^^^ Naturally occurring mutations in insulin receptor substrate 1 ( IRS 1 ) have previously been implicated in impaired insulin action . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The following cellular processes were observed in vitro in a manner dependent on insulin , time of incubation , and exogenous ATP : 1 ) autophosphorylation and activation of the insulin receptor ; 2 ) tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) ; 3 ) association of tyrosine phosphorylated IRS 1 with phosphoinositide 3 kinase ; 4 ) activation of the kinase Akt via its phosphorylation on Thr 308 and Ser 473 ; and 5 ) phosphorylation of glycogen synthase kinase 3 by activated Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin receptor substrates 1 ( IRS 1 ) and 3 ( IRS 3 ) and phosphatidylinositol 3 kinase ( PI 3 kinase ) activity in adipose cells , which occurs in the presence of a weak stimulation of insulin receptor kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Identification of an in vitro insulin receptor substrate 1 phosphorylation site by negative ion muLC / ES API CID MS hybrid scan technique . ^^^ Based on this study , we now applied an improved method for the identification of phosphorylation sites in insulin receptor substrate 1 , an important mediator in insulin signal transduction which was phosphorylated in vitro by protein kinase C zeta . ^^^ During the liquid chromatography ( LC ) / ES MS experiment , the phosphopeptides of the enzymatic digest mixture of the studied insulin receptor substrate 1 fragment were detected under high skimmer potential ( API CID ) using phosphorylation specific m / z 79 marker ions as well as the intact m / z values of the peptides which were recorded under low skimmer potential . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation and Western blot analyses detected reduced levels of tyrosyl phosphorylated IRbeta , tyrosyl phosphorylated insulin receptor substrate 1 ( IRS 1 ) , and p 85 associated IRS 1 but no alterations in IRbeta , IRS 1 , or p 85 protein expression in cerebellar tissue from ethanol exposed pups . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Exposure to IGF 1 for 30 minutes or E 2 for 20 minutes increased insulin receptor substrate 1 ( IRS 1 ) association with the regulatory ( p 85 ) subunit of PI3K , enhanced tyrosine phosphorylation of p 85 , and increased PI3K activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nuclear translocation of insulin receptor substrate 1 by the insulin receptor in mouse embryo fibroblasts . ^^^ Translocation of the insulin receptor substrate 1 ( IRS 1 ) to the nuclei has been reported to occur in cells stimulated by insulin like growth factor 1 ( IGF 1 ) or expressing certain viral and cellular oncogenes . ^^^ Only the A isoform of the insulin receptor ( IR ) can induce IRS 1 nuclear translocation , which is significant when the receptor is over expressed . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in tumor necrosis factor treated cells through targeting multiple serine kinases . ^^^ In this study , we analyzed the effects of aspirin ( acetylsalicylic acid ) on serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) in cells treated with tumor necrosis factor ( TNF ) alpha . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
As compared with the wild type , insulin stimulated phosphorylation of the insulin receptor ( IR ) and insulin receptor substrate 1 was significantly reduced , and activities of phosphatidylinositol 3 kinase and glycogen synthase were low in transgenic muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Because the other known PH PTB proteins ( insulin receptor substrates : IRS 1 , IRS 2 , IRS 3 , and IRS 4 , and the downstream of kinases : DOK 1 , DOK 2 , and DOK 3 ) are substrates of insulin and insulin like growth factor ( IGF ) 1 receptors , we asked whether these new proteins , termed IRS5 / DOK4 and IRS6 / DOK5 , might also have roles in insulin and IGF 1 signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Hyperosmotic stress inhibits insulin receptor substrate 1 function by distinct mechanisms in 3T3 L 1 adipocytes . ^^^ We show here that , despite normal activation of insulin receptor , hyperosmotic stress inhibits both tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and IRS 1 associated phosphoinositide 3 ( PI 3 ) kinase activity in response to physiological insulin concentrations . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We report here that human melanoma M 2 cells lacking FLNa expression exhibited normal insulin receptor ( IR ) signaling , whereas FLNa expressing A 7 cells were unable to elicit insulin dependent Shc tyrosine phosphorylation and p42 / 44 MAPK activation despite no significant defect in IR stimulated phosphorylation of insulin receptor substrate 1 or activation of the phosphatidylinositol 3 kinase / AKT cascade . ^^^ Expression of FLNaCT had no major effect on insulin induced phosphorylation of the IR , insulin receptor substrate 1 , or AKT , but it elicited changes in actin cytoskeletal structure and ruffle formation in HepG 2 cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The ability of GH to stimulate lipogenesis and tyrosine phosphorylation of the GH receptor ( GHR ) , Janus kinase 2 ( Jak 2 ) , insulin receptor substrate 1 ( IRS 1 ) and 2 ( IRS 2 ) was greatly reduced in refractory as compared to responsive primary rat adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Physiological hyperinsulinaemia increased tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 by approximately 2 . 5 fold , IRS 1 associated phosphatidylinositol 3 kinase ( PI 3 kinase ) activity by approximately 2 fold and Akt ( protein kinase B ) phosphorylation by approximately 3 fold , with similar responses between healthy subjects and CHF patients . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The activities of DAQ B 1 and over a dozen related structures were studied for insulin receptor ( IR ) and insulin receptor substrate 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Constitutive over expression of the insulin receptor substrate 1 causes functional up regulation of Fas receptor . ^^^ BACKGROUND / AIMS : Insulin and insulin growth factor 1 stimulated signaling through the insulin receptor substrate 1 ( IRS 1 ) promotes hepatocellular proliferation and survival . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Reduced activation of phosphatidylinositol 3 kinase and increased serine 636 phosphorylation of insulin receptor substrate 1 in primary culture of skeletal muscle cells from patients with type 2 diabetes . ^^^ When compared with cells from control subjects , myotubes established from patients with type 2 diabetes presented the same defects as those previously evidenced in vivo in muscle biopsies , including defective stimulation of phosphatidylinositol ( PI ) 3 kinase activity , decreased association of PI 3 kinase with insulin receptor substrate ( IRS ) 1 and reduced IRS 1 tyrosine phosphorylation during insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Globular adiponectin increased glucose uptake in adipocytes without stimulating tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 , and without enhancing phosphorylation of Akt on Ser 473 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Impact of genetic background on development of hyperinsulinemia and diabetes in insulin receptor / insulin receptor substrate 1 double heterozygous mice . ^^^ To evaluate the influence of genetic background on development of diabetes in a genetically susceptible host , we generated mice that are double heterozygous ( DH ) for knockout of the insulin receptor and insulin receptor substrate 1 on three genetic backgrounds ( C57BL / 6 [ B 6 ] , 129Sv , and DBA ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mice double heterozygous ( DH ) for deletion of insulin receptor and insulin receptor substrate 1 are lean , insulin resistant , and have a phenotype that strongly depends on the genetic background of the mouse . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the MCF 7 breast cancer cell line , insulin like growth factors ( IGFs ) are known to elicit antiproliferative actions via the insulin receptor substrate 1 ( IRS 1 ) / PI 3 kinase / AKT pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
E 2 treatment of breast cancer cells alters expression of nearly all of the IGF family members including IGF 1 , IGF 2 , IGF binding proteins , IGF type 1 receptor ( IGF RI ) , and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Et 3 , 4 dephostatin increased the tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) , with or without insulin , in differentiated 3T3 L 1 mouse adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin is a potent inducer of adipogenesis , and differentiation of adipocytes requires many components of the insulin signaling pathway , including the insulin receptor substrate IRS 1 and phosphatidylinositol 3 kinase ( PI3K ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We now report that insulin receptor substrate 1 and the p110alpha catalytic subunit of PI 3 K ( but not p110beta ) also colocalize with the actin structures . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It has been reported that insulin receptor substrate ( IRS ) 1 deficient ( IRS 1 / ) mice showed insulin resistance without type 2 diabetes , whereas the IRS 2 deficient ( IRS 2 / ) mice showed insulin resistance with type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth hormone acts at several levels to block insulin actions including inhibiting phosphorylation of the insulin receptor and one of its principal signaling molecules IRS 1 in response to insulin administration . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Gly972Arg variant in the insulin receptor substrate 1 gene and association with Type 2 diabetes : a meta analysis of 27 studies . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nuclear matrix association of insulin receptor and IRS 1 by insulin in osteoblast like UMR 106 cells . ^^^ In the present study , we explored to determine whether insulin has any effect on the nuclear translocation of insulin receptor and IRS 1 in the nucleus of UMR 106 cells . ^^^ Insulin receptor and IRS 1 appeared to be translocated to the nucleus in a time dependent manner by insulin whereas Akt levels remained unchanged by insulin treatment . ^^^ The majority of insulin receptor and IRS 1 translocated to the nucleus appeared to associate with nuclear matrix . ^^^ Confocal laser scanning microscope ( CLSM ) analysis also supports the nuclear translocation of insulin receptor and IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , VEGFR 2 , insulin receptor substrate 1 , and c Src were also involved in VEGF A induced activation of PI 3 kinase , resulting in the compensation in cells expressing kinase inactive c Fes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In breast cancer cells , 17 beta estradiol ( E 2 ) upregulates the expression of insulin receptor substrate 1 ( IRS 1 ) , a molecule transmitting insulin like growth factor 1 ( IGF 1 ) signals through the PI 3K / Akt survival pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
TGF beta 1 affected IGF 1 stimulated insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation and its association with Grb 2 protein . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
High levels of palmitic acid lead to insulin resistance due to changes in the level of phosphorylation of the insulin receptor and insulin receptor substrate 1 . ^^^ We measured the changes in protein phosphorylation in samples from abdominus rectus muscle and there was a decrease of 64 and 75 % in the levels of phosphorylation in tyrosine of the insulin receptor and insulin receptor substrate 1 , respectively . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Arg 972 variant in insulin receptor substrate 1 is associated with an atherogenic profile in offspring of type 2 diabetic patients . ^^^ The insulin receptor substrate 1 ( IRS 1 ) gene has been considered a candidate for insulin resistance , type 2 diabetes , and coronary artery disease . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regulation of insulin receptor substrate 1 in the liver , skeletal muscle and adipose tissue of rats throughout pregnancy . ^^^ Considerable evidence indicates that insulin receptor substrate 1 could play an important role in insulin sensitivity . ^^^ It seems possible that the gestational hormonal milieu could affect insulin receptor substrate 1 . ^^^ In the present study , measurements of tyrosine phosphorylation and protein content of insulin receptor substrate 1 and gene expression in the liver , skeletal muscle and adipose tissue in the rat indicated that , during pregnancy , significant changes occurred in these parameters . ^^^ We found in early gestation that muscle and adipose tissue were highly sensitive to insulin action , because the phosphorylation of insulin receptor substrate 1 is greater than in late gestation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Vanadate regulates the insulin mitogenic effect by modulating SHP 2 association with insulin receptor substrate 1 in JAr human choriocarcinoma cells . ^^^ In this study we investigated , in JAr cells , the effect of a protein tyrosine phosphatase inhibitor , vanadate , on the insulin receptor substrate 1 ( IRS 1 ) mitogen activated protein kinase ( MAPK ) pathway and on cell proliferation in the presence of normal or high glucose concentration . ^^^ However , vanadate treatment reverted the effect of high glucose on basal and insulin stimulated insulin receptor and IRS 1 phosphorylation . ^^^ This action is related to a modulation of the SHP 2 association with IRS 1 that in turn might regulate the phosphorylation state of the main substrates involved in mitogenesic signaling of the insulin receptor . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This results in reduction of tyrosine phosphorylation of the insulin receptor substrate 1 and inhibits activation of phosphoinositol 3 kinase , an enzyme that is essential for normal insulin stimulated glucose uptake . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The four proteins studied were the insulin receptor substrate 1 ( IRS 1 ) , the ID 2 protein , nucleolin , and the upstream binding factor ( UBF ) , all of which are involved directly or indirectly in the differentiation program . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Before RSG treatment , insulin infusion did not significantly increase insulin receptor tyrosine phosphorylation ( 0 . 95 + / 0 . 10 to 1 . 08 + / 0 . 13 density units ; NS ) but had a small stimulatory effect on insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation ( 1 . 05 + / 0 . 10 to 1 . 21 + / 0 . 12 density units ; P < 0 . 01 ) and the association of p 85 with IRS 1 ( 0 . 94 + / 0 . 06 to 1 . 08 + / 0 . 06 activity units ; P < 0 . 01 ) . ^^^ RSG therapy had no effect on basal or insulin stimulated insulin receptor tyrosine phosphorylation but increased insulin stimulation of IRS 1 tyrosine phosphorylation ( 1 . 13 + / 0 . 11 to 1 . 56 + / 0 . 17 density units ; P < 0 . 01 vs . prerosiglitazone ) and p 85 association with IRS 1 ( 1 . 00 + / 0 . 06 to 1 . 27 + / 0 . 07 activity units ; P < 0 . 05 vs . prerosiglitazone ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signaling through insulin receptor substrate 1 and 2 in normal liver development . ^^^ The purpose of this study was to determine the roles of the insulin receptor substrate ( IRS 1 and IRS 2 ) mediated growth cascades in rapidly growing fetal rat liver . ^^^ METHODS : We determined the expression and tyrosyl phosphorylation of the insulin receptor beta subunit ( IRbeta ) , IRS 1 and IRS 2 , the binding of phosphatidylinositol 3 kinase ( PI3K ) , and activation of the mitogen activated protein kinase ( MAPK ) pathway in the presence or absence of insulin stimulation in vivo during development and in the adult liver . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PIP4K 2 beta expression did not impair insulin dependent association of PI3K with insulin receptor substrate 1 ( IRS 1 ) but abbreviated Akt activation , indicating that PIP4K 2 regulates PI 3 , 4 , 5 P 3 degradation rather than synthesis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , and phosphatidylinositol 3 kinase ( PI 3 kinase ) was significantly higher in the HE / EX and LE / C groups compared with the HE / C group . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Polymorphism of insulin receptor substrate 1 gene in patients with coronary heart diseases ] . ^^^ OBJECTIVE : To explore the relationship between the polymorphism of insulin receptor substrate 1 ( IRS 1 ) gene and coronary heart diseases in Chinese population . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study , we generated knockout mice lacking both Kir6 . 2 and insulin receptor substrate 1 ( IRS 1 ) . ^^^ Because IRS 1 is the major substrate of insulin receptor kinase , we expected disruption of the IRS 1 gene to reduce glucose uptake in Kir6 . 2 knockout mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Relationship between the mutation of insulin receptor substrate 1 gene 3 ' untranslated region and type 2 diabetes in the Chinese ] . ^^^ OBJECTIVE : To study the relationship between the mutation of the insulin receptor substrate 1 ( IRS 1 ) gene 3 ' untranslated region and Type 2 diabetes in the Chinese . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A novel insulin analog with unique properties : LysB 3 , GluB 29 insulin induces prominent activation of insulin receptor substrate 2 , but marginal phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , glucose uptake , insulin receptor substrate 1 ( IRS 1 ) phosphorylation and glucose transporter 4 ( GLUT 4 ) translocation in muscle were reduced in response to insulin during suckling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) plays an essential role in mediating the insulin signals that trigger mitogenesis , lipid synthesis , and uncoupling protein 1 gene expression in mouse brown adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This effect of IL 6 was accompanied by a marked reduction in IRS 1 , but not IRS 2 , protein expression , and insulin stimulated tyrosine phosphorylation , whereas no inhibitory effect was seen on the insulin receptor tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin induced increases in tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 and the binding of PI 3 kinase to IRS 1 were decreased approximately 60 % in epitrochlearis muscles exposed to glucosamine . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of transcription factors associated with adipogenesis ( peroxisome proliferator activated receptor gamma , CAAT / enhancer binding protein alpha ) and lipogenesis ( carbohydrate response element binding protein , adipocyte determination and differentiation dependent factor 1 / sterol regulatory element binding protein 1c ) , as well as of adipose differentiation markers ( adipocyte lipid binding protein , perilipin , lipoprotein lipase ) , lipogenic enzymes ( glycerol 3 phosphate acyltransferase , acyl CoA : diacylglycerol acyltransferase 1 and 2 , fatty acid synthase , ATP citrate lyase ) and insulin signaling proteins ( insulin receptor , insulin receptor substrate 1 , GLUT 4 ) , was suppressed in WAT but not in BAT of HSL / mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
AngII induced Janus kinase 2 tyrosine phosphorylation and coimmunoprecipitation with insulin receptor substrate 1 ( IRS 1 ) and IRS 2 as well as an increase in tyrosine phosphorylation of IRS and its association with growth factor receptor binding protein 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Growth factor specific regulation of insulin receptor substrate 1 expression in MCF 7 breast carcinoma cells : effects on the insulin like growth factor signaling pathway . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a key protein in the IGF signaling pathway in the estrogen dependent MCF 7 breast carcinoma cell line . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It is suggested that FFAs interfere with insulin signalling via PKC induced serine phosphorylation of the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Transcript levels of genes required for the activation of PKB / Akt ( insulin like growth factor 1 , insulin receptor substrate 1 ) were measured by quantitative RT PCR . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vivo , insulin / GlcN rats had decreased ( P < . 01 ) whole body glucose uptake ( 37 . 7 + / 2 . 1 5 49 . 7 + / 2 . 7 mg 10 kg ( 1 ) 10 min ( 1 ) in respect to insulin / saline ) , receptor autophosphorylation ( 37 + / 5 5 82 + / . 0 arbitrary units / mg protein ) , and insulin receptor substrate 1 ( IRS 1 ) phosphorylation ( 112 % + / 15 % 5 198 % + / 23 % of saline infusion rats ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Inhibition of net HepG 2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3 kinase , independent of insulin receptor substrate 1 phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Among the down regulated genes , we focused on the genes encoding cyclin D 1 , proliferating cell nuclear antigen , and the insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of insulin receptor substrate 1 serine 307 correlates with JNK activity in atrophic skeletal muscle . c Jun NH ( 2 ) terminal kinase ( JNK ) has been shown to negatively regulate insulin signaling through serine phosphorylation of residue 307 within the insulin receptor substrate 1 ( IRS 1 ) in adipose and liver tissue . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of IRS 1 ( insulin receptor substrate protein 1 ) on certain serine residues , including S 307 and S 612 in rodent IRS 1 ( equivalent to S 312 and S 616 in human IRS 1 ) , has been shown to play a negative role in insulin signalling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Role of the insulin like growth factor I / insulin receptor substrate 1 axis in Rad 51 trafficking and DNA repair by homologous recombination . ^^^ This effect involves an interaction between Rad 51 and the major IGF IR signaling molecule , insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This enhancement seemed to be attributable to its ability to increase the duration of IGF 1 stimulated receptor and insulin receptor substrate 1 ( IRS 1 ) phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
OBJECTIVE : To investigate the effect of Bushen Tongmai recipe ( BSTMR ) on the tyrosine phosphorylation of insulin receptor ( InsR ) and insulin receptor substrate 1 ( IRS 1 ) after insulin stimulation in muscle and fat tissues of insulin resistant ( IR ) rats induced by high fat forage . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , overexpression of wild type or dominant negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers , phosphorylations of insulin receptor , insulin receptor substrate 1 , or Akt and mitogen activated protein kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
MAP kinases and mTOR mediate insulin induced phosphorylation of insulin receptor substrate 1 on serine residues 307 , 612 and 632 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Modulation of human insulin receptor substrate 1 tyrosine phosphorylation by protein kinase Cdelta . ^^^ Non esterified fatty acid ( free fatty acid ) induced activation of the novel PKC ( protein kinase C ) isoenzymes PKCdelta and PKCtheta correlates with insulin resistance , including decreased insulin stimulated IRS 1 ( insulin receptor substrate 1 ) tyrosine phosphorylation and phosphoinositide 3 kinase activation , although the mechanism ( s ) for this resistance is not known . ^^^ In the present study , we have explored the possibility of a novel PKC , PKCdelta , to modulate directly the ability of the insulin receptor kinase to tyrosine phosphorylate IRS 1 . ^^^ Activated PKCdelta was also found to inhibit the IRS 1 tyrosine phosphorylation in vitro by purified insulin receptor using recombinant full length human IRS 1 and a partial IRS 1 glutathione S transferase fusion protein as substrates . ^^^ These results indicate that PKCdelta modulates the ability of the insulin receptor to tyrosine phosphorylate IRS 1 by direct phosphorylation of the IRS 1 molecule . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This effect correlated with the potentiation by rosiglitazone of insulin stimulated Tyr phosphorylation of insulin receptor substrate 1 and to a greater extent of insulin receptor substrate 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Indeed , insulin induces the following : ( 1 ) tyrosine phosphorylation of the insulin receptor , the insulin receptor substrate 1 ( IRS 1 ) and G ( 1 ) alpha ( 2 ) ; ( 2 ) co precipitation of IRS 1 with G ( 1 ) alpha ( 2 ) but not with other G alpha subunits . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Kaempferol treatment also led in a dose dependent decrease in the expression of progesterone receptor ( PgR ) , cyclin D 1 , and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 and 2 ( IRS 1 and IRS 2 ) , two major downstream molecules of IGF 1R , are known to be important in the genesis of diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Compared with the LCC 6 WT cells , LCC 6 DN cells failed to phosphorylate the adaptor proteins insulin receptor substrate 1 and 2 in response to IGF 1 and did not activate Akt after exposure to IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
VS treatment also prolonged the insulin stimulated activation of phosphatidylinositol 3 kinase ( PI 3 K ) , which was associated with sustained interaction between insulin receptor substrate 1 ( IRS 1 ) and the p ( 85 alpha ) subunit of phosphatidylinositol 3 kinase ( PI 3 K ) in response to insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have reported that the protein tyrosine kinase Fer is associated with signaling complexes containing insulin receptor substrate 1 ( IRS 1 ) and phosphatidylinositol 3 kinase ( PI 3 kinase ) in insulin stimulated 3T3 L 1 adipocytes [ J . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nutrient dependent and insulin stimulated phosphorylation of insulin receptor substrate 1 on serine 302 correlates with increased insulin signaling . ^^^ Ser / Thr phosphorylation of insulin receptor substrate IRS 1 regulates insulin signaling , but the relevant phosphorylated residues and their potential functions during insulin stimulated signal transduction are difficult to resolve . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The role of insulin receptor substrate 1 gene ( IRS 1 ) in type 2 diabetes in Pima Indians . ^^^ The insulin receptor substrate 1 ( IRS 1 ) is a critical element in insulin signaling pathways , and mutations in the IRS 1 gene have been reported to have a role in determining susceptibility to traits related to type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor ( IR ) levels were modestly reduced by 19 % ( P < 0 . 01 ) in TG mice , but there were no changes in phosphorylation of IR or IR substrate 1 ( IRS 1 ) between WT and TG mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Fatty acid induced insulin resistance : role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling . ^^^ Tyrosine phosphorylation of IRS 1 ( insulin receptor substrate 1 ) and its binding to PI 3 kinase ( phosphoinositide 3 kinase ) are critical events in the insulin signalling cascade leading to insulin stimulated glucose transport . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Down regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway , including insulin receptor substrate 1 ( IRS 1 ) associated phosphoinositide 3 kinase ( PI3K ) , Akt kinase serine phosphorylation and activity and glucose transporter ( GLUT 4 ) protein content , are evident in skeletal muscle after eccentric exercise . ^^^ Recent studies have shown that TNF alpha can increase IRS 1 serine / threonine phosphorylation , which impairs IRS 1 docking to the insulin receptor , and this inhibits insulin signalling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The relationship between the Gly972Arg polymorphism in the insulin receptor substrate 1 ( IRS 1 ) gene and metabolic risk markers is not clear , possibly due to small sample sizes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A highly conserved NTRK 3 C terminal sequence in the ETV 6 NTRK3 oncoprotein binds the phosphotyrosine binding domain of insulin receptor substrate 1 : an essential interaction for transformation . ^^^ EN transformation is associated with constitutive tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , the phosphorylation of the insulin receptor substrate 1 ( IRS 1 ) , Akt , and mitogen activated protein ( MAP ) kinase were identical in the tumorous and normal mammary tissues . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein ( PC ) 1 K121Q and insulin receptor substrate 1 ( IRS 1 ) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In muscle , loss of p50alpha / p55alpha results in reduced levels of insulin stimulated insulin receptor substrate 1 ( IRS 1 ) and phosphotyrosine associated PI 3 kinase but enhanced levels of IRS 2 associated PI 3 kinase and Akt activation , whereas in adipocytes levels of both insulin stimulated PI 3 kinase and Akt are unchanged . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In these activated lymphocytes , insulin binding to its receptor also caused an 83 % upregulation of phosphorylated insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Lack of association of the Gly972Arg mutation of the insulin receptor substrate 1 gene with coronary artery disease in the Austrian population . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
DPI inhibited the insulin stimulated tyrosine phosphorylation of the insulin receptor and IRS 1 / 2 , and also reduced the association of Grb 2 with IRS 1 , suggesting that the effect of DPI on MAP kinase activation occurred downstream of the IR and IRS proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin gene ( INS ) , insulin receptor gene ( INSR ) and insulin receptor substrate 1 gene ( IRS 1 ) have been proposed as candidate genes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In 3T3 L 1 adipocytes , DHEA increases tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 and IRS 2 and stimulates IRS 1 and IRS 2 associated phosphatidylinositol ( PI ) 3 kinase activity with no effects on either insulin receptor or Akt phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signals are mediated by tyrosine phosphorylation of the insulin receptor and its downstream targets , such as Irs 1 and Irs 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we examined the individual roles of insulin and amino acids in the activation of insulin signaling components leading to translation initiation , specifically , the insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 kinase ( PI 3 kinase ) , protein kinase B ( PKB ) and ribosomal protein S 6 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Apart of its insulin like effects , hyperosmolarity can lead to cellular insulin resistance mediated by both prevention of PKB activation and inhibition of the Insulin Receptor Substrate 1 ( IRS 1 ) function . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
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: P06213 and P35568 Pubmed SVM Score :0.0
The type 1 insulin like growth factor receptor ( IGF IR ) and its docking protein , insulin receptor substrate 1 ( IRS 1 ) , play important roles in cell transformation , cell differentiation and aging . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : Insulin stimulated phosphorylation of insulin receptor ( IR beta ) , insulin receptor substrates ( IRS 1 and IRS 2 ) , association of phosphatidylinositol 3 kinase ( PI 3 kinase ) , Ser 473 phosphorylation of Akt and Thr202 / Tyr204 phosphorylated p44 / 42 MAP kinase in 3T3L1 adipocytes and FAO hepatoma cells incubated with increasing concentrations of saquinavir for 24 , 36 hours , 2 , 3 and 6 days were measured . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Kinetics and extents of insulin stimulated insulin receptor and IRS 1 tyrosine phosphorylation were similar in wild type and PTPalpha ( / ) liver , muscle , and adipose tissue . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These observations correlated with opposite changes exerted by native and oxidized LDL on the insulin receptor substrate 1 ( IRS ) associated PI 3 kinase / Akt response to IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found 31 % ( p < 0 . 0001 ) and 38 % ( p < 0 . 001 ) decreased protein levels of insulin receptor beta ( IRbeta ) subunit and insulin receptor substrate 1 ( IRS 1 ) , respectively , in GK rat hearts with 37 % ( p < 0 . 02 ) and 45 % ( p < 0 . 01 ) lower insulin stimulated tyrosine phosphorylation of these proteins . ^^^ CONCLUSION : We conclude that decreased insulin receptor beta , IRS 1 and GLUT 4 proteins are associated with insulin resistance in type 2 diabetic rat hearts . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In cells incubated with IGFBP 3 , both total and insulin receptor substrate 1 ( IRS 1 ) associated PI 3 kinase activities were rapidly stimulated , with maximal effects after 3 and 10min of incubation , respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The early steps of insulin receptor ( IR ) signaling ( tyrosine phosphorylation of IR beta subunit , IRS 1 and Shc and PI 3 ' kinase activity ) have been characterized in two target tissues in the chicken : liver and muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) at 12 . 5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS 1 achieved at 50 microM of TZDs or 400 microM of metformin . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Adenovirus mediated expression of Nox 4 deletion constructs lacking NAD ( P ) H or FAD / NAD ( P ) H cofactor binding domains acted in a dominant negative fashion in differentiated 3T3 L 1 adipocytes and attenuated insulin stimulated H ( 2 ) O ( 2 ) generation , insulin receptor ( IR ) and IRS 1 tyrosine phosphorylation , activation of downstream serine kinases , and glucose uptake . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Deficiency of insulin receptor substrate 1 impairs skeletal growth through early closure of epiphyseal cartilage . ^^^ Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate 1 ( IRS 1 ) showed IRS 1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin dependent association of the p 85 subunit of phosphatidylinositol 3 kinase with insulin receptor substrate 1 was hampered and the phosphorylation of Akt / glycogen synthase kinase 3alpha / beta was significantly impaired after stimulation with insulin or with platelet derived growth factor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent : Gly972Arg in the insulin receptor substrate 1 ( IRS 1 ) gene , Glu23Lys in the potassium inwardly rectifying channel gene ( KCNJ 11 ) , and Pro12Ala in the peroxisome proliferative activated receptor gamma 2 gene ( PPARG 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The acute lipid lowering effect of leptin on livers from lean animals was mediated by a PI 3 kinase dependent mechanism , because wortmannin and LY 294002 , the PI 3 kinase inhibitors , blocked the effects of leptin on hepatic triglyceride levels and leptin increased liver PI 3 kinase activity by 183 + / 6 % ( p = 0 . 003 ) and insulin receptor substrate 1 tyrosine phosphorylation by 185 + / 30 % ( p = 0 . 02 ) in the absence of PI 3 kinase inhibitors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
RECENT FINDINGS : Common polymorphisms in the PC 1 , insulin receptor substrate 1 and 2 , and PPAR gamma 2 genes have been linked to insulin resistance and dyslipidaemia , although the results have not been consistent . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Surprisingly , the expression of glucose transporters 1 and 4 and insulin receptor substrate 2 was increased and that of pyruvate dehydrogenase kinase 4 and insulin receptor substrate 1 was reduced . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
For the purpose of this review , four molecules ( adiponectin [ APM 1 ] , stearoyl CoA desaturase 1 [ SCD 1 ] , insulin receptor substrate 1 [ IRS 1 ] , peroxisome proliferator activated receptor gamma [ PPARG ] ) , each with a plausible role in the disease process , have been selected to illustrate the use of such techniques in humans . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and its binding to phosphatidylinositol 3 kinase ( PI 3 kinase ) are critical events in the insulin signalling cascade leading to insulin stimulated glucose transport . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vitro phosphorylation of insulin receptor substrate 1 by protein kinase C zeta : functional analysis and identification of novel phosphorylation sites . ^^^ Here we used an in vitro approach to identify PKC zeta phosphorylation sites within insulin receptor substrate 1 ( IRS 1 ) and to characterize the functional implications . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 and 2 ( IRS 1 and IRS 2 ) : what a tangled web we weave . ^^^ The insulin receptor is a transmembrane tyrosine kinase that is essential for mediating multiple intracellular signalling cascades that lead ultimately to the biological actions of insulin Tyrosine phosphorylation o f the cytosolic proteins insulin receptor substrate 1 and 2 ( IRS 1 and IRS 2 ) produces protein ' scaffolding ' for the assembly of effector proteins containing Src homology 2 ( SH 2 ) domains , thereby generating multisubunit signalling complexes . ^^^ Although IRS 1 was originally isolated as a specific insulin receptor substrate , both IRS 1 and IRS 2 appear to play a broader role , functioning also as proximal substrates in growth hormone and cytokine receptor signalling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Acidosis impairs insulin receptor substrate 1 associated phosphoinositide 3 kinase signaling in muscle cells : consequences on proteolysis . ^^^ Insulin receptor substrate 1 ( IRS 1 ) associated PI3K activity was not altered in cells acidified for 10 min but was strongly inhibited in cells incubated at pH 7 . 1 for 24 h . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This increase in glucose transport correlated with enhanced insulin stimulated activities of phosphatidylinositol 3 kinase , protein kinase B ( or Akt ) , and protein kinase Clambda ( PKC lambda ) , three key molecules in the insulin signaling pathway , and was associated with decreased levels of serine phosphorylated insulin receptor substrate 1 ( IRS 1 ) , a molecule implicated in insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Islet secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco ( endo ) plasmic reticulum Ca2+ ATPase ( SERCA ) 2b and 3 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Parental 32D cells and 32D IGF IR cells ( expressing increased levels of the type 1 insulin like growth factor 1 [ IGF 1 ] receptor [ IGF IR ] ) do not express insulin receptor substrate 1 ( IRS 1 ) or IRS 2 . 32D IGF IR cells differentiate when the cells are shifted from IL 3 to IGF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The cellular content of insulin receptor substrate 1 and phosphatidylinositol 3 kinase did not differ significantly between the depots , but the expression of protein kinase B ( PKB ) tended to be increased in omental compared with s . c . adipocytes ( P = 0 . 09 ) . ^^^ Dexamethasone treatment decreased the expression of insulin receptor substrate 1 ( by approximately 40 % ; P < 0 . 05 ) and PKB ( by approximately 20 % ; P < 0 . 05 ) in omental but not in s . c . adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Colocalization of insulin receptor and insulin receptor substrate 1 to caveolae in primary human adipocytes . ^^^ Part of insulin receptor substrate 1 ( IRS 1 ) , the immediate downstream signal mediator , was colocalized with the insulin receptor in the plasma membrane and caveolae , as demonstrated by immunofluorescence microscopy , immunogold electron microscopy , and immunogold electron microscopy of transfected recombinant HA IRS 1 . ^^^ Insulin stimulated phosphorylation of the insulin receptor and IRS 1 was not affected , indicating that caveolae integrity is required downstream of IRS 1 . ^^^ In conclusion we show that insulin receptor and IRS 1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Instead , IL 1beta inhibited the ability of IGF 1 to phosphorylate tyrosine residues on both of its downstream docking proteins , insulin receptor substrate 1 and insulin receptor substrate 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , TGFalpha but not IGF 1 induced rapid phosphorylation of Shc , whereas only IGF 1 activated insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The inhibition in PKB was not due to a loss in insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation , IRS 1 / p85 ( phosphoinositide 3 kinase ) association or suppression in phosphatidyl 3 , 4 , 5 triphosphate synthesis , but was attributable to an elevated intracellular synthesis of ceramide ( 6 fold ) from palmitate and a concomitant activation of protein kinase PKCzeta ( 5 fold ) . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
The insulin like growth factor I / insulin receptor substrate 1 axis controls , in a nonredundant way , approximately 50 % of cell and body size in animals from Drosophila to mice and in cells in culture . ^^^ We have previously shown that insulin receptor substrate 1 ( IRS 1 ) translocates to the nuclei and nucleoli , where it binds to the upstream binding factor ( UBF ) 1 , a regulator of RNA polymerase 1 activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In streptozotocin mice , in both retina and liver , insulin receptor ( IR ) and insulin receptor substrate ( IRS ) 2 protein and tyrosine phosphorylation were increased by insulin , while IRS 1 protein and its phosphorylation were maintained . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tissue specific differences in activation of atypical protein kinase C and protein kinase B in muscle , liver , and adipocytes of insulin receptor substrate 1 knockout mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 / SHP 2 interaction , a phenotype dependent switching machinery of insulin like growth factor 1 signaling in vascular smooth muscle cells . ^^^ In differentiated VSMCs , IGF 1 activated a protein tyrosine phosphatase , SHP 2 , recruited by insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
As the biological effects of Pes 1 are similar to those of the insulin receptor substrate 1 ( IRS 1 ) , we investigated the interactions of Pes 1 with IRS 1 itself and with the SV 40 T antigen . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The site of interference with the Ras / ERK and PI 3 K / Akt signaling is downstream of the TrkB receptor and involves docking proteins insulin receptor substrate 1 and Shc , which convey receptor activation to the downstream effectors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The NIH PPAR gamma cells express functionally active components of the insulin receptor signaling pathway ( the insulin receptor , IRS 1 , phosphatidylinositol 3 kinase , and Akt 2 ) at levels comparable to those in responsive cell lines . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated glucose transport requires activation of phosphatidylinositol ( PI ) 3 kinase ( 3K ) , operating downstream of insulin receptor substrate 1 . ^^^ Relative to adipocytes of lean women , insulin stimulated [ ( 3 ) H ] 2 deoxyglucose uptake and activation of insulin receptor substrate 1 / PI3K and aPKCs , but not PKB , were diminished in adipocytes of obese women . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signalling is inhibited by the phosphorylation of serine and threonine residues at the levels of the insulin receptor and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein levels and phosphorylation of the insulin receptor and insulin receptor substrate 1 / 2 ( IRS 1 / 2 ) were measured , as was the association between IRS 1 / 2 and phosphatidylinositol 3 kinase ( PI3K ) . ^^^ Insulin receptor and IRS 1 / 2 protein levels and insulin induced tyrosine phosphorylation of the insulin receptor were unaltered . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased insulin receptor substrate 1 serine phosphorylation and stress activated protein kinase / c Jun N terminal kinase activation associated with vascular insulin resistance in spontaneously hypertensive rats . ^^^ Insulin stimulated tyrosine phosphorylation of insulin receptor and IRS 1 in SHR was decreased to 55 % ( P < 0 . 01 ) and 40 % ( P < 0 . 01 ) of the levels in Wistar Kyoto rats ( WKY ) , respectively . ^^^ Serine phosphorylated IRS 1 that was immunoprecipitated from the aorta of SHR was capable of inhibiting in vitro tyrosine phosphorylation by recombinant insulin receptor compared with WKY derived IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nevertheless , S6K1 deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from S6K1 to insulin receptor substrate 1 ( IRS 1 ) , which blunts S 307 and S636 / S639 phosphorylation ; sites involved in insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
One consequence of obesity is that JNK phosphorylates the adapter protein insulin receptor substrate 1 ( IRS 1 ) on Ser 307 and inhibits signaling by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Systemic deletion of SH 2 B impaired insulin receptor activation and signaling in the liver , skeletal muscle , and fat , including tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and IRS 2 and activation of the phosphatidylinositol 3 kinase / Akt and the Erk1 / 2 pathways . ^^^ Moreover , SH 2 B directly enhanced autophosphorylation of insulin receptor and tyrosine phosphorylation of IRS 1 and IRS 2 in an SH 2 domain dependent manner in cultured cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SH 2 B promotes insulin receptor substrate 1 ( IRS 1 ) and IRS 2 mediated activation of the phosphatidylinositol 3 kinase pathway in response to leptin . ^^^ Here we report that SH 2 B , a JAK 2 interacting protein , promotes activation of the PI 3 kinase pathway by recruiting insulin receptor substrate 1 ( IRS 1 ) and IRS 2 in response to leptin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nuclear insulin receptor substrate 1 interacts with estrogen receptor alpha at ERE promoters . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a major signaling molecule activated by the insulin and insulin like growth factor 1 receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We examined the effect of losartan on the expression of insulin receptor substrate 1 ( IRS 1 ) , protein kinase B ( PKB ) and glucose transporter 4 ( GLUT 4 ) , as well as the phosphorylation status of IRS 1 and the association between IRS 1 and phosphatidylinositol ( PI ) 3 kinase in skeletal muscle from fat fed and streptozotocin ( STZ ) treated rats , an animal model of type 2 diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These diabetes related abnormalities in glucose disposal were associated with a marked diminution in the insulin mediated enhancement of protein kinase B ( Akt / PKB ) and insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinostol 3 kinase ( PI 3 kinase ) activities ; these two kinases are key elements in the insulin signalling pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor ( IR ) , tyrosine autophosphorylation , and insulin receptor substrate ( IRS ) 1 protein content in addition to the significant decrease in IRS 1 tyrosine phosphorylation in soleus muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To analyze the roles of insulin receptor substrate ( IRS ) proteins in insulin stimulated cell cycle progression , we examined the functions of rat IRS 1 and IRS 3 in Chinese hamster ovary cells overexpressing the human insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
There was no change in the protein expression of insulin receptor beta subunit ( IR beta ) , insulin receptor substrate 1 ( IRS 1 ) , IRS 2 , the p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 kinase ) , Akt , and glucose transporter protein 4 ( GLUT 4 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , exercise training did not enhance the ability of insulin to stimulate insulin receptor substrate 1 ( IRS 1 ) associated phosphatidylinositol 3 ( PI 3 ) kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Chronic administration of CT 1 to 3T3 L 1 adipocytes resulted in a decrease of both fatty acid synthase and insulin receptor substrate 1 protein expression yet did not effect the expression of a variety of other adipocyte proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Ex vivo biochemical studies of mediobasal hypothalamic tissue revealed that insulin stimulated the association of insulin receptor substrate 1 with the p85alpha subunit of PI3K and also tyrosine phosphorylation of p 42 and p 44 subunits of MAPK in the hypothalamus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Inhibition of phosphatidylinositol 3 kinase enhances insulin stimulation of insulin receptor substrate 1 tyrosine phosphorylation and extracellular signal regulated kinases in mouse R fibroblasts . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , IGF 1 induced IGF IR and insulin receptor substrate 1 phosphorylation were greatly impaired in ATM deficient cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
PI 3 kinase appeared to be present in high abundance and , in response to insulin , recruitment to the insulin receptor tyrosine kinase ( IR ) of IRS 1 and PI 3 kinase was observed . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , 28 genes showed such marked upregulation in the diabetic group exclusively ( including inflammatory / transcription activators MYC , IL 8 , IL 1beta , growth factor vascular endothelial growth factor , amphiregulin , and glucose metabolism involved gene insulin receptor substrate 1 ) , and 27 genes in the nondiabetic group only , including glycogen binding subunit PPP1R3C . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Stable transfection of murine 32D myeloid cells ( which lack endogenous IRS proteins and are insensitive to growth inhibition by IGFBP 3 ) with IRS 1 or IRS 2 cDNA confers sensitivity to growth inhibition by IGFBP 3 ; this IRS mediated growth inhibition can be completely reversed by insulin in 32D cells stably expressing IRS 2 and the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A 5 hour lipid infusion decreased insulin stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40 50 % decreases in insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and IRS 1 associated PI3K activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we show that the compensatory islet growth response to insulin resistance in 2 models insulin receptor ( IR ) / IR substrate 1 ( IRS 1 ) double heterozygous mice and liver specific IR KO ( LIRKO ) mice is severely restricted by PDX 1 heterozygosity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
At 3 weeks after injury , glucose production by the liver and utilization by skeletal muscle was measured under insulin clamp conditions , insulin receptor binding was measured in skeletal muscle , liver and adipose tissue membranes and IRS 1 expression was measured by Western blot methods . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
At 29 weeks of age , GSK 3beta protein levels were 5 fold higher , and glycogen synthase activation ( 27 % ) , glycogen levels ( 58 % ) and insulin receptor substrate 1 ( IRS 1 ) protein levels ( 67 % ) were significantly reduced in skeletal muscle . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
This is the result of downregulation of the insulin receptor substrates , IRS 1 and IRS 2 , which become limiting for signal transmission from the insulin receptor to PI3K . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In contrast , exercise training failed to modify the levels of insulin receptor ( IR ) , IRS 1 , and IR tyrosine autophosphorylation in obese Zucker rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study , we determined whether beta arrestin 1 is involved in insulin induced insulin receptor substrate 1 ( IRS 1 ) degradation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein kinase C ( PKC ) beta modulates serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) effect of overexpression of PKCbeta on insulin signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin secretion in women who have polycystic ovary syndrome and carry the Gly972Arg variant of insulin receptor substrate 1 in response to a high glycemic or low glycemic carbohydrate load . ^^^ OBJECTIVE : We evaluated metabolic parameters in Chilean women with polycystic ovary syndrome ( PCOS ) who were carriers and non carriers of the glycine to arginine substitution at codon 972 ( Gly972Arg ) variant of insulin receptor substrate 1 and to assess insulin response after oral high and low glycemic loads METHODS : In 146 women with PCOS and 97 healthy women ( HW ) , Gly972Arg genotypes were obtained by polymerase chain reaction , and an oral glucose tolerance test was performed with glucose and insulin measurements . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylated PDGFR , IR , and insulin receptor substrate 1 all immunoprecipitated with SHIP . ^^^ Expression of WT and DeltaIP mutant SHIP did not affect tyrosine phosphorylation of either the insulin or the PDGF receptor , or the expression of insulin receptor substrate 1 and Shc proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This stress in turn leads to suppression of insulin receptor signaling through hyperactivation of c Jun N terminal kinase ( JNK ) and subsequent serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Selective activation of insulin receptor substrate 1 and 2 in pleural mesothelioma cells : association with distinct malignant phenotypes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we found that , in brown adipose tissue ( BAT ) , another insulin sensitive tissue , the basal tyrosine phosphorylations of insulin receptor ( IR ) and IR substrates ( IRS 1 and IRS 2 ) were upregulated in SCD 1 ( / ) mice compared with wild type mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study , we examined the protein levels and phosphorylation state of insulin receptor ( IR ) , IRS 1 and IRS 2 , the association between IRSs and PI3K and SHP 2 , the insulin induced IRSs associated PI 3 kinase activities , and the phosphorylation status of AKT and atypical PKCzeta / lambda in the liver and the muscle of 6 month old Wistar rats treated with DHEA . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Once induced , SOCS 3 interacts with the insulin receptor , JAK 2 , IRS 1 , and IRS 2 . ^^^ The inhibition of SOCS 3 expression by a phosphorthioate modified antisense oligonucleotide partially restores angiotensin 2 induced inhibition of insulin induced insulin receptor , IRS 1 and IRS 2 tyrosine phosphorylation , and IRS 1 and IRS 2 association with p 85 phosphatidylinositol 3 kinase and [ Ser 473 ] phosphorylation of Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor , insulin receptor substrate 1 , Raf 1 , and Mek 1 during hormonal hepatocarcinogenesis by intrahepatic pancreatic islet transplantation in diabetic rats . ^^^ Thus , we investigated FAHs , HCAs , and HCCs for altered expression of insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , Raf 1 and Mek 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Acetylation of insulin receptor substrate 1 is permissive for tyrosine phosphorylation . ^^^ These effects were confirmed using RNA interference against HDAC 2 , indicating that HDAC 2 specifically prevents phosphorylation of IRS 1 by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have shown previously that insulin receptor substrate 1 ( IRS 1 ) can translocate to the nuclei and nucleoli of cells and bind UBF 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In order to test the validity of this hypothesis , we mated GPC 3 knockout mice with insulin receptor substrate 1 ( IRS 1 ) nullizygous mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of the insulin receptor , insulin receptor substrate 1 , and the p 85 subunit of phosphatidylinositol 3 kinase doubled at 30 min and gradually returned to control values by 240 min . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Functionally perturbed IR signaling was confirmed with the absence of insulin stimulated insulin receptor substrate 1 tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Short term in vivo inhibition of insulin receptor substrate 1 expression leads to insulin resistance , hyperinsulinemia , and increased adiposity . ^^^ Insulin receptor substrate 1 ( IRS 1 ) has an important role as an early intermediary between the insulin and IGF receptors and downstream molecules that participate in insulin and IGF 1 signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Conversely , adenoviral mediated overexpression of PTP 1B in HepG 2 cells downregulated the phosphorylation of insulin receptor and insulin receptor substrate 1 and caused increases in cellular and secreted apoB 100 as a result of increased intracellular apoB 100 stability . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Metformin also increased hepatic basal IkappaBalpha levels ( by 260 % ; P < 0 . 001 ) but had no effect on tyrosine phosphorylation or expression of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association testing in 9 , 000 people fails to confirm the association of the insulin receptor substrate 1 G972R polymorphism with type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association studies of insulin receptor substrate 1 gene ( IRS 1 ) variants in type 2 diabetes samples enriched for family history and early age of onset . ^^^ The gene encoding insulin receptor substrate 1 ( IRS 1 ) represents a strong biological candidate for a contributory role in type 2 diabetes susceptibility . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In addition , insulin receptor substrate 2 ( IRS 2 ) protein levels were reduced in IUGR placentas , with no changes in IRS 1 or Shc protein content , and this was associated with a parallel decrease in IRS 2 associated phosphatidyl inositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Serine 332 phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 attenuates insulin signaling . ^^^ The ability of glycogen synthase kinase 3 ( GSK 3 ) to phosphorylate insulin receptor substrate 1 ( IRS 1 ) is a potential inhibitory mechanism for insulin resistance in type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activation of mTOR / S6K1 by insulin was associated with a rapamycin sensitive increase in Ser636 / 639 phosphorylation of insulin receptor substrate ( IRS ) 1 but , surprisingly , did not result in impaired IRS 1 associated phosphatidylinositol ( PI ) 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although insulin receptor substrate 1 ( IRS 1 ) and IRS 2 , among other factors , activate PI3K , there is little information on the relative roles of IRS 1and IRS 2 during aPKC activation by insulin action in specific cell types . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This population has shown a high prevalence of type 2 diabetes mellitus , and the aim of this study was to analyze the relationship between the Pst 1 ( insulin gene ) , Nsi 1 ( insulin receptor gene ) and Gly972Arg ( insulin receptor substrate 1 gene ) polymorphisms and type 2 diabetes mellitus , obesity and hypertension in this population . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Another action of JNK , phosphorylation at Ser ( 307 ) of insulin receptor substrate 1 , was also predicted to contribute to the repression of adipogenesis . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Human insulin receptor substrate 1 ( IRS 1 ) polymorphism G972R causes IRS 1 to associate with the insulin receptor and inhibit receptor autophosphorylation . ^^^ The most commonly detected polymorphism in human insulin receptor substrate 1 ( IRS 1 ) , a glycine to arginine change at codon 972 ( G972R ) , is associated with an increased risk of Type 2 diabetes and insulin resistance . ^^^ Pull down experiments indicated that there was an association between the IRS 1 ( 925 1008 ) peptide and the insulin receptor that was markedly enhanced by the presence of the G972R polymorphism . ^^^ The use of additional overlapping fragments localized this interaction to domains between residues 950 986 of IRS 1 and residues 966 1271 of the insulin receptor , containing the tyrosine kinase domain of the receptor . ^^^ In addition , the IRS 1 ( 925 1008 ) G972R peptide acted as a competitive inhibitor of insulin receptor and insulin like growth factor 1 receptor autophosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The growth and survival signals of IGF IR are mediated through multiple intracellular pathways , many of which emanate from insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Time course studies also revealed that mTOR and S6K1 activation by insulin was accelerated in tissues of obese rats , in association with increased inhibitory phosphorylation of insulin receptor substrate 1 ( IRS 1 ) on Ser636 / Ser639 and impaired Akt activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
At the cellular level , vanadium activates several key elements of the insulin signal transduction pathway , such as the tyrosine phosphorylation of insulin receptor substrate 1 , and extracellular signal regulated kinase 1 and 2 , phosphatidylinositol 3 kinase and protein kinase B activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In HepG 2 cells transduced with adeno associated viral ( AAV ) vectors encoding LFv2IRE , AP 20187 induces LFv2IRE homodimerization and transphosphorylation minutes after drug administration , resulting in the phosphorylation of a canonical substrate of the insulin receptor tyrosine kinase , IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tumors from AS [ S ] ODN treated mice showed a decrease in IGF IR expression and in insulin receptor substrate 1 tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 , PKB , and downstream metabolic effects , but not insulin stimulated tyrosine phosphorylation of insulin receptor , exhibited insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The G972R variant of the insulin receptor substrate 1 ( IRS 1 ) gene is associated with insulin resistance in `` uncomplicated ' ' obese subjects evaluated by hyperinsulinemic euglycemic clamp . ^^^ Several association studies have indicated the insulin receptor substrate 1 ( IRS 1 ) gene G972R variant as a genetic risk factor for insulin resistance , particularly in presence of obesity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Importantly , there were significant reductions ( approximately 30 50 % ) in insulin stimulation of tyrosine phosphorylation of the insulin receptor beta subunit and insulin receptor substrate 1 ( IRS 1 ) , IRS 1 associated with the p 85 subunit of phosphatidylinositol 3 kinase , Akt Ser 473 phosphorylation , and Ser 9 phosphorylation of glycogen synthase kinase 3beta in epitrochlearis and soleus muscles of TG ( mREN 2 ) 27 rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
With this in mind , we supposed that the G972A variant of insulin receptor substrate 1 ( IRS 1 ) may modulate the response to metformin treatment in women with polycystic ovary syndrome ( PCOS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Maximal insulin stimulation ( 5 mU / ml ) of glucose transport activity , glycogen synthase activity , and selected insulin signaling factors [ tyrosine phosphorylation of insulin receptor ( IR ) and IRS 1 , IRS 1 associated with p 85 subunit of phosphatidylinositol 3 kinase , and serine phosphorylation of Akt and GSK 3 ] were assessed . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Because activation of PKB can require insulin receptor substrate proteins ( IRS 1 and IRS 2 ) and phosphatidylinositol 3 kinase ( PI3K ) , it is of interest to determine whether the activity of Foxo 1 is also regulated by heterotrimeric G protein coupled receptors ( GPCRs ) with IRS 1 or 2 , PI3K , or PKB signaling potential . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Here we show that in 3T3 L 1 adipocytes , resistin attenuates multiple effects of insulin , including insulin receptor ( IR ) phosphorylation , IR substrate 1 ( IRS 1 ) phosphorylation , phosphatidylinositol 3 kinase ( PI3K ) activation , phosphatidylinositol triphosphate production , and activation of protein kinase B / Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Of these , the gene encoding insulin receptor substrate 1 ( IRS 1 ) , the protein product of which has been previously reported to be decreased , missing , altered , or defective in persons with type 2 diabetes mellitus , was evaluated by real time quantitative PCR to corroborate the array data . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS AND RESULTS : Western blot analysis and real time polymerase chain reaction revealed alpha and beta subunits of the insulin receptor in association with insulin receptor substrate 1 and phosphatidylinositol 3 kinase in the media of the aorta and carotid artery . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We measured insulin receptor amount and insulin dependent receptor autophosphorylation as well as insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation as an index of insulin signaling . ^^^ Likewise , we determined that insulin dependent insulin receptor and IRS 1 tyrosine phosphorylation was not significantly different in the four cell lines representing parental , low , medium , and high levels of caveolin 1 expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
To answer this question we assessed carbohydrate handling and tissue specific function of the insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) during prolonged GH treatment of obese rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
OBJECTIVE : To determine whether frequencies of the mutations in the 21 hydroxylase ( CYP 21 ) gene and the G972R variant of the insulin receptor substrate 1 ( IRS 1 ) gene are increased in women with polycystic ovary syndrome ( PCOS ) and adrenal androgen ( AA ) excess . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We now found that impairment of glimepiride induced lipolytic cleavage of GPI proteins in rat adipocytes by the novel inhibitor of glycosylphosphatidylinositol specific phospholipase C ( GPI PLC ) , GPI 2350 , caused almost complete blockade of ( 1 ) dissociation from caveolin 1 of pp 59 ( Lyn ) and GPI proteins , ( 2 ) their redistribution from high cholesterol ( hcDIGs ) to low cholesterol containing ( lcDIGs ) lipid rafts , ( 3 ) tyrosine phosphorylation of pp 59 ( Lyn ) and insulin receptor substrate 1 protein ( IRS 1 ) and ( 4 ) stimulation of glucose transport as well as ( 5 ) inhibition of isoproterenol induced lipolysis in response to glimepiride . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In many cases , insulin resistance in liver is associated with reduced expression of both major insulin receptor substrate ( IRS ) proteins , IRS 1 and IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mechanism of feedback regulation of insulin receptor substrate 1 phosphorylation in primary adipocytes . ^^^ Serine and threonine phosphorylation of IRS 1 ( insulin receptor substrate 1 ) has been reported to decrease its ability to be tyrosine phosphorylated by the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interleukin 4 enhanced activity of MAPK , Akt 1 , and Stat 3 in IL 4 responsive , but not in IL 4 unresponsive MIA PaCa 2 cells ; however , IL 4 enhanced tyrosine phosphorylation of insulin receptor substrate 1 and 2 in all cell lines . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We have also showed that insulin and leptin are able to activate PI3K through IRS 1 ( insulin receptor substrate 1 ) and IRS 2 respectively . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced tyrosine phosphorylation of the IR beta subunit and insulin receptor substrate 1 ( IRS 1 ) were increased in the muscle , but not in the liver of APS treated TIIDM rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The present study evaluated whether this training induced enhancement of muscle glucose transport is associated with upregulation of critical insulin signaling elements , including insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 kinase , Akt , and glycogen synthase kinase 3 . ^^^ However , the protein expression and functionality of tyrosine phosphorylation of insulin receptor and IRS 1 , IRS 1 associated with the p 85 regulatory subunit of phosphatidylinositol 3 kinase , and Ser 473 phosphorylation of Akt were not altered by exercise training . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tumor necrosis factor ( TNF ) contributes to insulin resistance by binding to the 55kDa TNF receptor ( TNF R 55 ) , resulting in serine phosphorylation of proteins such as insulin receptor ( IR ) substrate ( IRS ) 1 , followed by reduced tyrosine phosphorylation of IRS 1 through the IR and , thereby , diminished IR signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Differential regulation of insulin receptor substrate 1 degradation during mannitol and okadaic acid induced apoptosis in human neuroblastoma cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
As compared with control , PCOS granulosa cells had higher insulin receptor substrate 1 ( IRS 1 ) expression , but lower IRS 2 expression . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This review will provide insight on the current understanding of the regulation of insulin signaling in both physiological and pathological conditions through modulations that occur with regards to the functions of the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Loss of insulin receptor substrate 1 signaling induces the cardiovascular and proteo ( fibrino ) lytic system derangements typical of insulin resistance . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is one mediator of insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We found that latrunculin treatment did not affect insulin dependent tyrosine phosphorylation of the insulin receptor beta subunit and IRS 1 but completely inhibited activation of Akt / PKB enzymatic activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Treatment of control rats with BRL 37344 led to higher insulin induced tyrosine phosphorylation of the insulin receptors , insulin receptor substrate ( IRS ) 1 and ERK , higher insulin induced IRS 1 / PI3 kinase association , and higher [ Ser ( 473 ) ] phosphorylation of Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrates 1 and 2 ( IRS 1 and IRS 2 ) are pivotal in relaying insulin signaling in insulin responsive tissues such as muscle . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The insulin like effects are mediated by the cytosolic tyrosine kinase Janus kinase 2 ( JAK 2 ) upon GH GH receptor interaction , resulting in tyrosine phosphorylation of downstream targets including the GH receptor itself and insulin receptor substrate 1 ( IRS 1 ) and IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The Gly972Arg substitution of the insulin receptor substrate 1 ( IRS 1 ) gene and the Pro12Pro genotype of the peroxisome proliferator activated receptor gamma 2 ( PPARgamma 2 ) gene have been suggested to be associated with type 2 diabetes mellitus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This effect of Ras may occur through stabilization of a second messenger protein , insulin receptor substrate 1 , that mediates PI 3 kinase dependent signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In 3T3 L 1 adipocytes and / or in HEK 293 cells stably expressing recombinant IRS 1 protein ( insulin receptor substrate protein 1 ) , the peroxisome proliferator activated receptor gamma agonist rosiglitazone and aspirin promote insulin signalling by decreasing inhibitory IRS 1 serine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After insulin treatment , EtOH exposed rats had decreased tyrosine phosphorylation of the insulin receptor beta subunit and of insulin receptor substrate 1 ( IRS 1 ) , as well as reduced IRS 1 associated PI 3 kinase in the gastrocnemius muscle compared with control rats . ^^^ Muscle insulin binding and peptide contents of insulin receptor , IRS 1 , p 85 subunit of PI 3 kinase , Akt / PKB , and atypical PKC isoform zeta were not different between EtOH exposed rats and controls . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
S nitrosation of the insulin receptor , insulin receptor substrate 1 , and protein kinase B / Akt : a novel mechanism of insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mechanisms of reactive oxygen species dependent downregulation of insulin receptor substrate 1 by angiotensin 2 . ^^^ Recently , serine phosphorylation and degradation of insulin receptor substrate 1 ( IRS 1 ) were shown to inhibit Akt activation and reduce glucose uptake . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) and IRS 2 are known to transduce and amplify signals emanating from the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , the disease has a strong genetic component , but only a handful of genes have been identified so far : genes for calpain 10 , potassium inward rectifier 6 . 2 , peroxisome proliferator activated receptor gamma , insulin receptor substrate 1 , and others . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Fatty acids appear to cause this defect in glucose transport by inhibiting insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and IRS 1 associated phosphatidylinositol 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor substrate 1 and phosphorylation of tyrosine in adipose tissue of polycystic ovary syndrome ] . ^^^ OBJECTIVE : To study expression of insulin receptor substrate 1 ( IRS 1 ) and phosphorylation of tyrosine in adipose tissue of polycystic ovary syndrome ( PCOS ) to approach the mechanism of insulin resistance ( IR ) in PCOS at tissue and cellular level . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Glucose transporter 4 ( GLUT 4 ) and insulin receptor substrate 1 ( IRS 1 ) protein expression in the liver and skeletal muscle were detected using Western blotting . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In a rabbit model of pressure overload hypertrophy , GU ( ( 31 ) P NMR spectroscopy ) and total / phosphorylated insulin signaling intermediates were assayed : insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , phosphatidylinositol 3 kinase ( PI 3 k ) , GLUT 4 translocation and contractile function in an isolated heart ischemia / reperfusion model . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of Ser 24 in the pleckstrin homology domain of insulin receptor substrate 1 by Mouse Pelle like kinase / interleukin 1 receptor associated kinase : cross talk between inflammatory signaling and insulin signaling that may contribute to insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Treatment with iNOS inhibitor reversed fasting hyperglycemia with concomitant amelioration of hyperinsulinemia and improved insulin sensitivity in ob / ob mice . iNOS inhibitor also increased the protein expression of insulin receptor substrate ( IRS ) 1 and 2 1 . 5 and 2 fold , respectively , and enhanced IRS 1 and IRS 2 mediated insulin signaling in the liver of ob / ob mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin increased insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , IRS 1 associated phosphatidylinositol ( PI ) 3 kinase activity , and phosphorylation of Akt Ser 473 and AS 160 , a newly described Akt substrate that plays a role in GLUT 4 exocytosis , approximately 2 . 3 fold before treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrate 1 ( IRS 1 ) regulation is critical for activation of endothelial nitric oxide synthase ( eNOS ) in response to stimulation by insulin or fluid shear stress . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
BVR is both a substrate for insulin receptor ( IR ) tyrosine kinase ( IRK ) activity and a kinase for serine phosphorylation of IR substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
OBJECTIVE : To determine the effects of long term estrogen replacement treatment on blood pressure and expressions of insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) in myocardium . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Using pharmacological , biochemical , and cell biological approaches , we show that leptin induced platelet activation required activation of a signaling cascade that included the long form of the leptin receptor , three kinases [ Janus kinase 2 ( JAK 2 ) , phosphatidylinositol 3 kinase ( PI3K ) , and protein kinase B ( PKB / Akt ) ] , the insulin receptor substrate 1 ( IRS 1 ) , and the major human platelet cAMP phosphodiesterase phosphodiesterase 3A ( PDE3A ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Phosphorylation of the insulin receptor , IRS 1 , and Akt in response to insulin was also significantly enhanced in high glucose conditions , especially at submaximal insulin concentrations . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Neither the phosphorylation of insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) , nor its association with phosphatidylinositol 3 kinase ( PI 3 kinase ) , was affected by ethanol . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Disruption of the availability of amino acids induces a rapid reduction of serine phosphorylation of insulin receptor substrate 1 in vivo and in vitro . ^^^ Insulin receptor substrate 1 ( IRS 1 ) plays a pivotal role in insulin signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of insulin receptor substrate 1 in primary breast cancer and lymph node metastases . ^^^ BACKGROUND : Insulin receptor substrate 1 ( IRS 1 ) transmits signals from the insulin like growth factor 1 receptor ( IGF IR ) and insulin receptor ( IR ) and has been associated with the pathogenesis of cancer . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
At the lowest lipid infusion rate ( 30 ml / h ) , insulin receptor and insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation , phosphatidylinositol ( PI ) 3 kinase activity associated with IRS 1 , and Akt serine phosphorylation were all significantly impaired ( P < 0 . 05 0 . 01 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mitogen activated protein ( MAP ) kinases and Akt activities , and phosphorylation of insulin receptor substrate 1 ( IRS 1 ) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Unexpectedly , tyrosine phosphorylation of IR and insulin receptor substrate 1 ( IRS 1 ) was faint in the hypothalamus of lean and ob / ob mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Fatty acids appear to cause this defect in glucose transport by inhibiting insulin stimulated tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) and IRS 1 associated phosphatidylinositol 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The tyrosine phosphorylation levels of the insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) in response to insulin were significantly reduced within FF hamsters . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Initial attempts based on fusion of the luciferase to IGFR , and EYFP to IGFR , or to downstream signaling molecules , insulin receptor substrate 1 ( IRS 1 ) or protein tyrosine phosphatases 1B ( PTP 1B ) , failed . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This diabetes related suppression of skeletal muscle glucose utilization was associated with a decrease in insulin ' s ability to promote the phosphorylation of tyrosine residues of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
BMC were insulin resistant , showing a significant inhibition of IRS 1 association with the insulin receptor ( IR ) following insulin stimulation , a corresponding increase in PI 3 kinase association with the IR , and a slow and modest increase in GLUT 4 recruitment to the plasma membrane . ^^^
Interacting proteins: P06213 and P35568 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 . ^^^ 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 . ^^^ One mechanism recently identified to downregulate IGF 1 or insulin receptor signaling in diabetic models is IRS 1 Ser ( 312 ) phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interestingly , the inhibitory effect of Gab 1 siRNA could be rescued not only by expression of an exogenous mouse Gab 1 but also by an exogenous human Gab 2 and vice versa , but not by IRS 1 ( insulin receptor substrate 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance induced by IL 6 was associated with impaired expression of the insulin receptor ( IR ) , IR tyrosine autophosphorylation , IRS 1 protein content and IRS 1 tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Functional significance of type 1 insulin like growth factor mediated nuclear translocation of the insulin receptor substrate 1 and beta catenin . ^^^ We show by immunocoprecipitation and by confocal microscopy that beta catenin binds to and co localizes with the insulin receptor substrate 1 ( IRS 1 ) , a docking protein for both the insulin and the IGF 1 receptors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In skeletal muscle , diabetes induces activation of inhibitor kappaB kinase ( IKKbeta ) , a key cellular mediator of the response to inflammatory stimuli , and this impairs insulin signal transduction via the insulin receptor substrate phosphatidylinositol 3 OH kinase ( IRS 1 / PI3 kinase ) pathway . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vitro phosphorylation analysis revealed that , like insulin , FSE also induces tyrosine phosphorylation of a number of proteins including the insulin receptor , insulin receptor substrate 1 and p 85 subunit of PI 3 K , in both 3T3 L 1 adipocytes and human hepatoma cells , HepG 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
One possible mechanism could involve alterations in the phosphorylation of serine 307 of the insulin receptor substrate 1 ( IRS 1 ) via activation of stress kinase enzymes , including SAPK / JNK . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
RESULTS : The following single nucleotide polymorphisms were detected by digestion of PCR products with appropriate restriction enzymes : Gly972Arg of the insulin receptor substrate 1 gene , Pro12Ala of the proliferator activated receptor gamma gene , C 174G in the promoter of IL 6 gene , and G 866A in the promoter of uncoupling protein 2 gene . ^^^ Weight loss was lower in carriers of Gly972Arg insulin receptor substrate 1 genotype than Gly972Gly carriers , but not statistically significant ( P = 0 . 06 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Fructose delivery increased c jun N terminal kinase activity and serine 307 phosphorylation of insulin receptor substrate 1 and reduced tyrosine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Inhibition of p 38 , a member of the mitogen activated protein kinase family , has been shown to prevent the loss of GLUT 4 protein expression in insulin resistant adipocytes without improving insulin receptor substrate 1 ( IRS 1 ) protein levels and presumably insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Surprisingly , T antigen does not operate directly , but utilizes insulin receptor substrate 1 ( IRS 1 ) , which is the major signaling molecule for insulin like growth factor 1 receptor ( IGF IR ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
G protein coupled receptor kinase 2 mediates endothelin 1 induced insulin resistance via the inhibition of both Galphaq / 11 and insulin receptor substrate 1 pathways in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Other data suggest that angiotensin 2 inhibits the vasodilator effects of insulin through insulin receptor substrate 1 phosphorylation at Ser 312 and Ser 616 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Identification of insulin receptor substrate 1 serine / threonine phosphorylation sites using mass spectrometry analysis : regulatory role of serine 1223 . ^^^ Insulin receptor substrate 1 ( IRS 1 ) , an intracellular substrate of the insulin receptor tyrosine kinase , also is heavily phosphorylated on serine and threonine residues , and several serine phosphorylation sites alter the function of IRS 1 . ^^^ This mutation had no effect on association of IRS 1 with the insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Polymorphisms in the insulin receptor substrate 1 ( IRS 1 ) gene and the insulin receptor substrate 2 ( IRS 2 ) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non hyperandrogenic controls . ^^^ BACKGROUND : We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate 1 gene ( IRS 1 ) and the Gly1057Asp variant in IRS 2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome ( PCOS ) and healthy controls . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These foci contain the insulin receptor substrate ( IRS ) 1 adaptor molecule , and their formation requires the binding of p 85 to IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The higher PTPase inhibitory potential of the OVC was associated with more robust tyrosine phosphorylation of several cellular proteins , including the IRbeta subunit and insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Shp 2 is required for protein kinase C dependent phosphorylation of serine 307 in insulin receptor substrate 1 . ^^^ The function of insulin receptor substrate 1 ( IRS 1 ) , a key molecule of insulin signaling , is modulated by phosphorylation at multiple serine / threonine residues . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Biochemical analyses demonstrated that chronic Akt activation induces feedback inhibition of PI3K activity through both proteasome dependent degradation of insulin receptor substrate 1 ( IRS 1 ) and inhibition of transcription of IRS 1 as well as that of IRS 2 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In skeletal muscle , insulin receptor substrate 1 and Glut 4 are up regulated at the end of the food restriction period , just the opposite of what we found in adipose tissue . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association of Gly972Arg variant of insulin receptor substrate 1 with metabolic features in women with polycystic ovary syndrome . ^^^ OBJECTIVE : To examine the prevalence and the effects of Gly972Arg ( G972A ) variant of insulin receptor substrate 1 ( IRS 1 ) in women with polycystic ovary syndrome ( PCOS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : We employed single ( c myc , SV 40 Tag ) and established double [ insulin receptor substrate 1 ( IRS 1 / c myc ) and hepatitis Bx protein ( X / c myc ) ] transgenic lines and all developed HCC . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Increased serine / threonine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) is associated with cellular insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Using a rat hindlimb suspension model of atrophy , we have previously shown that an upregulation of JNK occurs in atrophic muscles and correlates with the degradation of insulin receptor substrate 1 ( IRS 1 ) ( Hilder TL , Tou JC , Grindeland RF , Wade CE , and Graves LM . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In this study , we investigated the role of GIP in accumulation of triglycerides into adipocytes and in fat oxidation peripherally using insulin receptor substrate ( IRS ) 1 deficient mice and revealed that IRS 1 ( / ) GIPR ( / ) mice exhibited both reduced adiposity and ameliorated insulin resistance . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , amino acid infusion increased the inhibitory insulin receptor substrate 1 phosphorylation at Ser 312 and Ser636 / 639 and decreased insulin induced phosphoinositide 3 kinase activity . ^^^ Our results suggest that overactivation of the mammalian target of rapamycin / S6 kinase 1 pathway and inhibitory serine phosphorylation of insulin receptor substrate 1 underlie the impairment of insulin action in amino acid infused humans . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A novel regulation of IRS 1 ( insulin receptor substrate 1 ) expression following short term insulin administration . ^^^ Attention has focused on early signalling events such as defective tyrosine phosphorylation of IRS 1 ( insulin receptor substrate 1 ) , a major target for the insulin receptor tyrosine kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The phosphorylation of Ser 318 of insulin receptor substrate 1 is not per se inhibitory in skeletal muscle cells but is necessary to trigger the attenuation of the insulin stimulated signal . ^^^ The Ser / Thr phosphorylation of insulin receptor substrate 1 ( IRS ) is one key mechanism to stimulate and / or attenuate insulin signal transduction . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Attenuation of insulin stimulated insulin receptor substrate 1 serine 307 phosphorylation in insulin resistance of type 2 diabetes . ^^^ We found that insulin stimulated phosphorylation of serine 307 ( corresponding to serine 302 in the murine sequence ) in the immediate downstream mediator protein of the insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , is required for efficient insulin signaling and that this phosphorylation is attenuated in adipocytes from patients with type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Interleukin 1alpha inhibits insulin signaling with phosphorylating insulin receptor substrate 1 on serine residues in 3T3 L 1 adipocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both saturated and n 6 polyunsaturated fat diets reduce phosphorylation of insulin receptor substrate 1 and protein kinase B in muscle during the initial stages of in vivo insulin stimulation . ^^^ The phosphorylation of insulin receptor at Tyr1162 / 1163 ( IR Tyr1162 / 1163 ) increased over 20 min of insulin infusion , whereas the downstream phosphorylation of insulin receptor substrate 1 Tyr 612 ( IRS 1 Tyr 612 ) peaked at 5 min and declined thereafter . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Expression of the Insulin Receptor Substrate 1 in primary tumors and lymph node metastases in breast cancer : correlations with Bcl xL and Bax proteins . ^^^ In our previous investigation Insulin Receptor Substrate 1 ( IRS 1 ) correlated with proliferation marker Ki 67 in human breast cancer . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
RESULTS : rhHGF activator improved the recovery of liver function after resection in cirrhotic liver as compared with the control group . rhHGF activator also enhanced the proliferating cell nuclear antigen labeling index and liver regeneration rate . rhHGF activator converted the proHGF to mature HGF , showing the maximal effect at 10 min after injection , which was followed by tyrosine phosphorylation of insulin receptor substrate ( IRS ) 1 , and the association of IRS 1 with c Met and phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Physical association between VEGF receptor 2 ( VEGF R 2 ) and insulin receptor substrate ( IRS 1 ) and phosphatidylinositol 3 ' kinase ( PI3K ) was induced by VEGF , which augmented PI3K activity in VEGF R 2 immunoprecipitates . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Coimmunoprecipitation studies demonstrated that IGF IR and insulin receptor substrate 1 associated with caveolin , a caveolar marker , in 3T3L1 and NWTb 3 cells . ^^^ 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: P06213 and P35568 Pubmed SVM Score :0.0
We demonstrate that transformation by T antigen of MEFs and several other cell lines requires an insulin receptor substrate 1 ( IRS 1 ) phosphorylated on tyrosines . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin regulates glucose transport by activating insulin receptor substrate 1 ( IRS 1 ) dependent phosphatidylinositol 3 kinase ( PI3K ) which , via increases in PI 3 , 4 , 5 triphosphate ( PIP ( 3 ) ) , activates atypical protein kinase C ( aPKC ) and protein kinase B ( PKB / Akt ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
TNF alpha infusion increases phosphorylation of p 70 S6 kinase , extracellular signal regulated kinase 1 / 2 , and c Jun NH ( 2 ) terminal kinase , concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Dihydrotestosterone inhibits insulin stimulated cyclin D 2 messenger ribonucleic acid expression in rat ovarian granulosa cells by reducing the phosphorylation of insulin receptor substrate 1 . ^^^ DHT treatment also reduced the insulin mediated insulin receptor substrate 1 and Raf 1 phosphorylation , the upstream molecules of ERK in insulin signaling pathway . ^^^ The present study therefore shows that the inhibitory effect of DHT on insulin stimulated granulosa cell proliferation occurs early in the signaling pathway at the level of insulin receptor substrate 1 phosphorylation , leading to reduced ERK phosphorylation and subsequent inhibition of cyclin D 2 mRNA expression . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Protein kinase C alpha regulates insulin action and degradation by interacting with insulin receptor substrate 1 and 14 3 3 epsilon . ^^^ Overexpression of 14 3 3epsilon in 3T3 hIR cells significantly reduced IRS 1 bound PKCalpha activity , without altering IRS 1 / PKCalpha co precipitation . 14 3 3epsilon overexpression also increased insulin stimulated insulin receptor and IRS 1 tyrosine phosphorylation , followed by increased activation of Raf 1 , ERK1 / 2 , and Akt / protein kinase B . ^^^ Consistently , selective depletion of 14 3 3epsilon by antisense oligonucleotides caused a 3 fold increase of IRS 1 bound PKCalpha activity and a similarly sized reduction of insulin receptor and IRS 1 tyrosine phosphorylation and signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It was recently reported that melatonin enhanced insulin receptor kinase and IRS 1 phosphorylation , suggesting the potential existence of signaling pathway cross talk between melatonin and insulin . ^^^ Because TNF alpha has been shown to impair insulin action by suppressing insulin receptor tyrosine kinase activity and its IRS 1 tyrosine phosphorylation in peripheral tissues such as skeletal muscle cells , it was speculated that melatonin might counteract TNF alpha associated insulin resistance in type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Additionally , induction of tyrosyl phosphorylation of insulin receptor substrate 1 observed on day 2 was not evident on day 16 of leptin infusion . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
SOM 230 also inhibited other actions of IGF 1 ( inhibition of apoptosis , phosphorylation of insulin receptor substrate 1 , and cell division ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Both DNA microarray and quantitative RT PCR analysis showed increase in insulin receptor substrate 1 ( Irs 1 ) expression in zinc supplemented cultures , while several key genes downstream of Irs 1 in the insulin signaling pathway , such as protein kinase B ( PKB / Akt ) and 3 phosphoinositide dependent protein kinase 1 ( Pdpk 1 ) did not show significant differences at the transcript level . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
A genetic defect of insulin action ( the g972R Insulin Receptor Substrate 1 variant ) may sustain endothelial dysfunction , the first defect of vascular homeostasis in the road to atherosclerosis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up regulating the insulin like growth factor receptor / insulin receptor substrate 1 / phosphatidylinositol 3 kinase cascade . ^^^ However , by also inhibiting an mTOR dependent serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , they may enhance insulin like growth factor 1 ( IGF 1 ) signaling and downstream phosphatidylinositol 3 kinase ( PI3K ) / AKT activation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The increased glycogen synthase activity occurs in spite of decreased signaling through the insulin receptor substrate 1 ( IRS 1 ) phosphoinositide ( PI ) 3 kinase Akt pathway and increased glycogen synthase kinase 3beta ( GSK3beta ) activity in the basal state . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
These effects were associated with significant reduction in IGF 1 secretion ; inhibition of IGF 1 induced cell cycle progression and insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation , along with an increase in sub G 1 peak by apigenin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Each of the three VO2+ chelates increased the tyrosine phosphorylation of proteins in response to insulin , including the beta subunit of the insulin receptor ( IRbeta ) and the insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The present study investigated the changes of IGF 1Rbeta and the key intracellular downstream protein insulin receptor substrate 1 ( IRS 1 ) by using SOD 1 ( G93A ) transgenic mice with continuous intrathecal IGF 1 treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The aims of this study were to determine : ( 1 ) whether HCB is co carcinogenic in a medium term assay of N nitroso N methylurea ( NMU ) induced mammary tumors in rats ; ( 2 ) the effect of HCB on insulin receptor ( IR ) , insulin like growth factor 1 receptor ( IGF IR ) and insulin receptor substrate 1 ( IRS 1 ) levels and on IRS 1 phosphorylation ; ( 3 ) microsomal and cytosolic Protein Tyrosine Kinase ( PTK ) activities in mammary glands and NMU induced tumors . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We further show that the C domains are responsible for the differential abilities of IGF 2 and IGF 1 to activate phosphorylation of insulin receptor substrate 1 and Akt , as well as their ability to induce migration and cell survival via the IR A . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Identification of the major site of O linked beta N acetylglucosamine modification in the C terminus of insulin receptor substrate 1 . ^^^ Signal transduction from the insulin receptor to downstream effectors is attenuated by phosphorylation at a number of Ser / Thr residues of insulin receptor substrate 1 ( IRS 1 ) resulting in resistance to insulin action , the hallmark of type 2 diabetes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Effects are mediated through a variety of mechanisms that include attenuation of key insulin signalling pathways and decreased tyrosine phosphorylation of insulin receptor substrates IRS 1 , SHC and G alpha q / 11 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Compared with lean control subjects , obese and type 2 diabetic subjects had reduced muscle glucose uptake ( P < 0 . 01 ) and decreased insulin stimulation of tyrosine phosphorylation of insulin receptor substrate 1 and its ability to associate with phosphatidylinositol 3 kinase ( P < 0 . 01 and P < . 05 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin induced insulin receptor substrate 1 tyrosine and protein kinase B serine phosphorylation were significantly reduced in the liver and muscle of fatty animals compared with their lean littermates . ^^^ There was no difference between lean and fatty animals , however , in insulin receptor substrate 1 and protein kinase B protein expression in the liver and muscle and no effect by atrasentan . ^^^
Interacting proteins: P06213 and P35568 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 ) . ^^^ IGF 1 and IGF 2 and insulin receptor substrate 1 immunoreactivity was higher in tumors from patients with preoperative prostate specific antigen serum levels 10 ng / mL or greater , and IGF 2 expression was correlated with Gleason score . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
OBJECTIVE : To determine the insulin receptor ( IR ) tyrosine kinase activity phosphorylation of exogenous substrate poly ( Glu 4 : Tyr 1 ) and insulin receptor substrate 1 expression in normal myometrium and leiomyoma . ^^^ Insulin receptor tyrosine kinase activity and substrate 1 ( IRS 1 ) expression in human myometrium and leiomyoma . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Rho kinase plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) in cultured vascular smooth muscle cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 ( IRS 1 ) was much lower in SK N BE ( 2 ) cells than in PC 12 cells when the cells were treated with insulin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
E 2 enhanced insulin induced tyrosine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , IRS 1 / p85 association , phosphorylation of Akt , and 2 deoxyglucose uptake at 10 ( 8 ) m , but inhibited these effects at 10 ( 5 ) m . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The gene expression profile of TC / ET cells indicated , among up regulated genes , an increase in expression of insulin like growth factor receptor 1 ( IGF IR ) and one of its major intracellular mediators , insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular scanning for mutations in the insulin receptor substrate 1 ( IRS 1 ) gene in Turkish with type 2 diabetes mellitus . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is an endogenous substrate for the insulin receptor tyrosine kinase , which plays a key role in insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This was followed by the inhibition of insulin stimulated IRbeta tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 ( IRS 1 ) and IRS 1 associated phosphatidylinositol 3 kinase ( PI 3 Kinase ) , phosphoinositide dependent kinase 1 ( PDK 1 ) phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Substitution for these tyrosines in p 85 resulted in loss of SHP 2 recruitment and was associated with a reduction in association of the p85 / p110 complex with insulin receptor substrate 1 . ^^^ SHP 2 recruitment to p 85 is required for IGF 1 stimulated association of the p85 / p110 complex with insulin receptor substrate 1 and for the subsequent activation of the PI 3 kinase pathway leading to increased cell migration . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This in turn triggers a kinase cascade which activates both IkappaB kinase beta ( IKK beta ) and c Jun N terminal kinase ( JNK ) , each of which can phosphorylate a key serine residue in IRS 1 , rendering it a poor substrate for the activated insulin receptor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
However , no significant improvements were observed for functionality of insulin signaling elements ( tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 [ IRS 1 ] , IRS 1 associated with the p 85 regulatory subunit of phosphatidylinositol 3 ' kinase , and Ser 473 of Akt ) in muscle of irbesartan treated animals , except for a 25 % increase ( P < . 05 ) in IRS 1 tyrosine phosphorylation in soleus . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
No diet effect was found on the expression of the insulin receptor and insulin receptor substrate 1 or on phosphatidylinositol 3 ' kinase activity , or on FAT / CD36 expression pattern , GLUT 4 translocation , or triglyceride distribution in either the basal or insulin stimulated situation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Glucose transport , insulin receptor ( IR ) , and IR substrate 1 ( IRS 1 ) phosphorylation , phosphatidylinositol 3 ' kinase ( PI3K ) activity , as well as Akt Ser 473 phosphorylation have been investigated at the end of the incubation period and after a further short term insulin stimulation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
MATERIALS AND METHODS : We studied 1 , 777 unrelated Scandinavian women ( 588 with GDM and 1 , 189 pregnant non diabetic controls ) for polymorphisms in the genes encoding potassium inwardly rectifying channel subfamily J , member 11 ( KCNJ 11 E23K ) , insulin receptor substrate 1 ( IRS 1 G972R ) , uncoupling protein 2 ( UCP 2 866G > A ) and calpain 10 ( CAPN 10 SNP43 and SNP 44 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate 1 and 2 . ^^^ Immunoblotting studies revealed serine phosphorylation of insulin receptor substrate 1 and 2 in PE placentas ( P < 0 . 001 ) with downstream impairment of insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Inappropriate degradation of insulin signaling molecules such as insulin receptor substrates ( IRS 1 and IRS 2 ) has been demonstrated in experimental diabetes , mediated in part through the up regulation of suppressors of cytokine signaling ( SOCS ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Regulation of GLUT 4 translocation by chromium did not involve known insulin signaling proteins such as the insulin receptor , insulin receptor substrate 1 , phosphatidylinositol 3 kinase , and Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Although insulin receptor protein level and phosphorylation were unaltered by resistin , production of IRS 1 , but not IRS 2 , was downregulated and a decreased tyrosine phosphorylation of IRS 1 was detected . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Polymorphic alleles of both IRS 1 and IRS 2 ( insulin receptor substrate 1 2 ) , alone or in combination , may have a functional impact on the insulin resistant component of PCOS . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Nutrients suppress phosphatidylinositol 3 kinase / Akt signaling via raptor dependent mTOR mediated insulin receptor substrate 1 phosphorylation . ^^^ Here , we demonstrate that nutrients suppress phosphatidylinositol 3 ( PI 3 ) kinase / Akt signaling via Raptor dependent mTOR ( mammalian target of rapamycin ) mediated phosphorylation of insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The mechanisms leading to this down regulation in oxidized cells are complicated , involving increased serine / threonine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) , impaired insulin stimulated redistribution of IRS 1 and phosphatidylinositol kinase between cytosol and low density microsomal fraction , followed by a reduced protein kinase B phosphorylation and GLUT 4 translocation to the plasma membrane . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin receptor substrates , including Irs 1 and Irs 2 , integrate insulin and IGF receptor signals with heterologous pathways to coordinate growth and metabolism . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The following parameters were examined : morphological analysis of endocrine pancreata by immunohistochemistry ; protein levels of insulin receptor , IRS 1 , IRS 2 , PI 3 kinase , Akt 1 , and Akt 2 ; and static insulin secretion in isolated pancreatic islets . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Genistein did not change the protein levels of insulin receptor substrate 1 ( IRS 1 ) , the p 85 regulatory subunit of phosphatidylinositol 3 kinase ( PI3K ) , or Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin signals damaged by TNFalpha were the impaired expressions of insulin receptor ( IR ) , tyrosine autophosphorylation in IR , and insulin receptor substrate ( IRS ) 1 protein , as well as a decrease of IRS 1 tyrosine phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
RNAi mediated silencing of insulin receptor substrate 1 ( IRS 1 ) enhances tamoxifen induced cell death in MCF 7 breast cancer cells . ^^^ Insulin receptor substrate 1 ( IRS 1 ) is a major downstream signaling protein for insulin and insulin like growth factor 1 ( IGF 1 ) receptors , conveying signals to PI 3K / Akt and ERK1 / 2 pathways . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This study examines the compartmentalization and the insulin induced translocation and tyrosine phosphorylation of insulin receptor substrates ( IRS 1 and IRS 3 ) in epididymal white adipose tissue from adult and insulin resistant old rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Stimulation of the insulin and insulin like growth factor 1 ( IGF 1 ) receptor activates the phosphoinositide 3 kinase / Akt / mTOR pathway causing pleiotropic cellular effects including an mTOR dependent loss in insulin receptor substrate 1 expression leading to feedback down regulation of signaling through the pathway . ^^^ We now show that mTOR inhibition induces insulin receptor substrate 1 expression and abrogates feedback inhibition of the pathway , resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative , RAD 001 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
After low number islet transplantation ( n = 450 ) , the liver acini downstream of the islets show insulin induced alterations : massive glycogen and / or fat accumulation , translocation of the insulin receptor , decrease in glucose 6 phosphatase activity , increase in expression of insulin like growth factor ( IGF ) 1 , IGF II / mannose 6 phosphate receptor , insulin receptor substrate 1 , Raf 1 , and Mek 1 , corresponding to clear cell preneoplastic foci of altered hepatocytes known from chemical hepatocarcinogenesis and identical to that in streptozotocin diabetic Lewis rats . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
It is interesting that the vanadium effect on these signaling systems is independent of insulin receptor protein tyrosine kinase activity , but it is associated with enhanced tyrosine phosphorylation of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
IRS 1 and IRS 2 are the major insulin receptor substrates leading to glucose homeostasis , and have distinct and overlapping roles in diverse organs . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The G972R variant of the insulin receptor substrate 1 gene impairs insulin signaling and cell differentiation in 3T3L1 adipocytes ; treatment with a PPARgamma agonist restores normal cell signaling and differentiation . ^^^ The insulin receptor substrate 1 ( IRS 1 ) plays a central role in insulin sensitivity , and association studies have shown that the IRS 1 G972R variant is a risk factor for insulin resistance . ^^^ In addition , we observed that the interaction between the insulin receptor ( IR ) and the IRS 1 G972R protein was increased and that the autophosphorylation of the IR was significantly inhibited in 3T3L1 G972R cells compared with 3T3L1 WT . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Evidence that the mouse insulin receptor substrate 1 belongs to the gene family on which the promoter is activated by estrogen receptor alpha through its interaction with Sp 1 . ^^^ In the present study , the molecular mechanism underlying the up regulatory effect of estradiol ( E 2 ) on mouse insulin receptor substrate 1 ( IRS 1 ) promoter was investigated in CHO cells on which the same promoter had first been functionally characterized . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistance , assessed by insulin and glucose tolerance tests , Ser ( 307 ) phosphorylation of insulin receptor substrate 1 , and activation of protein kinase B , was examined in control and DIO wild type ( WT ) , Mc3rKO and Mc4rKO C57BL / 6J mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In vivo insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation ( 50 % ) and IRS 1 associated phosphatidylinositol 3 ' kinase ( 79 % ) relative to fasting plasma insulin levels were significantly elevated ( P < 0 . 05 ) in plantaris muscles of GSK 3 inhibitor treated animals . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Moreover , compared to R EN cells , R+ EN cells show a dramatic increase in membrane localization of insulin receptor substrate 1 ( IRS 1 ) in association with EN . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
Quantification of phosphorylation of insulin receptor substrate 1 by HPLC ESI MS / MS . ^^^ Serine / threonine phosphorylation of insulin receptor substrate 1 ( IRS 1 ) regulates the function and subsequent insulin signaling of this protein . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Basal insulin receptor substrate ( IRS ) 1 Ser ( 312 ) and Ser ( 616 ) phosphorylation , IRS 1 associated phosphatidylinositol 3 kinase activity , and extracellular signal regulated kinase ( ERK ) 1 / 2 phosphorylation were elevated in pancreas kidney transplant recipients , coincident with fasting hyperinsulinemia . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Systemic leptin administration to ob / ob mice reverted the diabetic phenotype and improved tissue regeneration as well as the impaired expression of InsR , insulin receptor substrate 1 and insulin receptor substrate 2 , and downstream signaling ( phosphorylation of GS kinase and GS ) in late wounds and nonwounded skin of ob / ob mice . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Activation of insulin receptor substrates 1 and 2 ( IRS 1 / IRS 2 ) was studied in rat and human myoblasts and rat cardiomyocytes . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Consistent with these findings , insulin dependent phosphorylations of insulin receptor substrate 1 , Akt , and Bad were impaired in the cholesterol depleted MEFs . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Association of insulin receptor substrate 1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus . ^^^ OBJECTIVE : Insulin receptor substrate 1 ( IRS 1 ) expression and tyrosine phosphorylation is decreased during pregnancy . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
O ' Reilly et al . provide evidence that poor tumor response to rapamycins is the result of relieving mTOR mediated feedback inhibition of insulin receptor substrate 1 , and activation of Akt mediated survival . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Investigating the signaling pathway downstream of IGF 1R reveals that insulin receptor substrate 2 ( IRS 2 ) overexpression compensates for the lack of IGF 1R , whereas IRS 1 overexpression does not . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Low insulin like growth factor binding protein 2 expression is responsible for increased insulin receptor substrate 1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
This defect appears to be a result of intracellular lipid induced inhibition of insulin stimulated insulin receptor substrate ( IRS ) 1 tyrosine phosphorylation resulting in reduced IRS 1 associated phosphatidyl inositol 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : Since growth of HCC is mediated by signaling through the insulin receptor substrate , type 1 ( IRS 1 ) , we examined if AAH is a downstream gene regulated by insulin and IGF 1 in HCC cells . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We also characterized insulin signaling pathways believed to promote myocyte growth and interact with proliferative responses mediated by G protein coupled receptors , and we assessed myocardial insulin receptor substrate 1 ( IRS 1 ) and p 110 alpha catalytic and p 85 regulatory subunits of phospatidylinositol 3 kinase ( PI3K ) , Akt , MEK , ERK1 / 2 , and S 6 kinase 1 ( S6K1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Four weeks of diabetes reduced basal insulin receptor kinase , insulin receptor substrate ( IRS ) 1 / 2 associated phosphatidylinositol 3 kinase , and Akt kinase activity without altering insulin receptor or IRS 1 / 2 expression or tyrosine phosphorylation . ^^^ After 12 weeks of diabetes , constitutive insulin receptor autophosphorylation and IRS 2 expression were reduced , without changes in p42 / p44 mitogen activated protein kinase or IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the presence of JCV T antigen , insulin receptor substrate 1 ( IRS 1 ) translocated to the nucleus where it co localized with Rad 51 , possibly attenuating HRR . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the presence of insulin , however , this suppression was blunted , and adiponectin enhanced the insulin induced phosphorylations of the main downstream molecule insulin receptor substrate 1 and Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
During the next 12 24 months , many peri insular ductules progressed via tumor like cystic lesions to large cystic cholangiomas , accompanied by a translocation of the insulin receptor into the cytoplasm and an increase in expression of insulin related signaling proteins ( Insulin receptor substrate 1 , Raf 1 , Mek 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population not correlated with insulin receptor substrate 1 Gly972Arg / Ala513Pro polymorphism . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Sennidin A did not induce tyrosine phosphorylation of insulin receptor ( IR ) and insulin receptor substrate 1 ( IRS 1 ) , but induced phosphorylation of Akt and glucose transporter 4 ( GLUT 4 ) translocation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We studied insulin stimulated early responses in the insulin receptor ( IR ) , insulin receptor substrate 1 ( IRS 1 ) , and p 85 subunit of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin resistant muscle has defects at several steps of the insulin signaling pathway , including decreases in insulin stimulated insulin receptor and insulin receptor substrate 1 tyrosine phosphorylation , and phosphatidylinositol 3 kinase ( PI 3 kinase ) activation . ^^^ Weight loss and thiazolidinediones ( TZDs ) improve glucose disposal , in part , by increasing insulin stimulated insulin receptor and IRS 1 tyrosine phosphorylation and PI 3 kinase activity . ^^^
Interacting proteins: P06213 and P35568 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: P06213 and P35568 Pubmed SVM Score :0.0
We have previously demonstrated that the insulin resistance associated with inducible nitric oxide synthase ( iNOS ) induction in two different models of obesity , diet induced obesity and the ob / ob mice , is mediated by S nitrosation of proteins involved in insulin signal transduction : insulin receptor beta subunit ( IRbeta ) , insulin receptor substrate 1 ( IRS 1 ) , and Akt . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
TNF alpha significantly activated ASK 1 , increased serine phosphorylation of insulin receptor substrate ( IRS ) 1 , and decreased insulin stimulated tyrosine phosphorylation of IRS 1 and serine phosphorylation of Akt , and all of these effects were inhibited by overexpression of either UCP 1 or MnSOD . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Importantly , these deleterious effects of methylglyoxal are independent of reactive oxygen species produced by methylglyoxal but appear to be the direct consequence of an impairment of insulin induced insulin receptor substrate 1 tyrosine phosphorylation subsequent to the binding of methylglyoxal to these proteins . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Enterocytes from the fructose fed hamster exhibited normal activity of the insulin receptor but reduced levels of insulin receptor substrate 1 phosphorylation and mass and Akt protein mass . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
METHODS : Chondrocyte responsiveness to IGF 1 was assessed by 35S sulfate incorporation into proteoglycans ( PGs ) , via aggrecan messenger RNA expression , using quantitative real time polymerase chain reaction or insulin receptor substrate 1 ( IRS 1 ) tyrosine phosphorylation ( Western blot analysis ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The subcellular fractionation properties and function of insulin receptor substrate 1 ( IRS 1 ) are independent of cytoskeletal integrity . ^^^ The prototypical insulin receptor substrate , IRS 1 plays a central role in insulin signaling . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Denervation decreased the amounts of insulin receptor substrate 1 ( IRS 1 ) , phosphatidly inositol 3 phosphate kinase ( PI3K ) , and Akt 1 proteins in femora of Cbl b ( + / + ) mice , whereas the amounts of these IGF 1 signaling molecules in femora of Cbl b ( / ) mice were constant after denervation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Tumor necrosis factor alpha ( TNF alpha ) signaling through the IkappaB kinase ( IKK ) complex attenuates insulin action via the phosphorylation of insulin receptor substrate 1 ( IRS 1 ) at Ser 307 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Serine / threonine phosphorylation of the insulin receptor and insulin receptor substrate 1 , which downregulates insulin signaling , and the activation of AMP activated protein kinase , an inhibitor of protein synthesis , were unaffected by age and feeding in muscle and liver . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
We examined signals that could activate muscle proteolysis and found low values of both phosphatidylinositol 3 kinase ( PI3K ) activity and phosphorylated Akt that were related to phosphorylation of serine 307 of insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Consistent with these results , TNFalpha induces JNK binding to insulin receptor substrate 1 ( IRS 1 ) but is unable to inhibit IGF 1 induced IRS 1 tyrosine phosphorylation in myoblasts that are treated with the JNK peptide inhibitor . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
By contrast , Gbeta 1 knockdown leads to a significant decrease in the level of serine phosphorylation of the insulin receptor substrate IRS 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Neither short term ( 1 hour ) nor long term ( 24 hours ) treatment with leptin ( 60 nmol / L ) altered basal or insulin stimulated glucose uptake and oxidation , glycogen synthesis , insulin receptor substrate 1 tyrosine , Akt , or glycogen synthase kinase 3beta phosphorylation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Melatonin stimulates glucose transport via insulin receptor substrate 1 / phosphatidylinositol 3 kinase pathway in C2C12 murine skeletal muscle cells . ^^^ Melatonin also increased the phosphorylation level of insulin receptor substrate 1 ( IRS 1 ) and the activity of phosphoinositide 3 kinase ( PI 3 kinase ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Among the responsive sites , 20 were previously known to be tyrosine phosphorylated with insulin treatment , including sites on the insulin receptor and insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Molecular mechanisms of insulin resistance : serine phosphorylation of insulin receptor substrate 1 and increased expression of p85alpha : the two sides of a coin . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B / Akt require Rab 5 . ^^^ This inhibition of PKB / Akt activation was because of the impaired interaction between insulin receptor substrate 1 and the p85alpha subunit of phosphatidylinositol 3 kinase . ^^^ These results indicate a requirement of Rab 5 in presenting p 85 to insulin receptor substrate 1 . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Immunoprecipitation and Western blot analysis of insulin receptor substrate 1 ( IRS 1 ) revealed no changes in protein mass with OMA treatment . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In most cases these effects are mediated , at least in part , by insulin receptor substrates ( IRS ) , one of which is insulin receptor substrate 1 ( IRS 1 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
The TSC 1 TSC2 / Rheb / Raptor mTOR / S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin like growth factor 1 ( IGF 1 ) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 ( IRS 1 and 2 ) . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Furthermore , oxLDL increased Erk dependent phosphorylation of insulin receptor substrate 1 serine 616 that was prevented by inhibiting oxidant generation , Erk activation , or by the p21ras C118S mutant . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
DUSP 5 dephosphorylates Erk 1 and Erk 2 within the MAPK signaling cascade , which in turn affects serine 612 phosphorylation of insulin receptor substrate 1 ( p 612 IRS 1 ) . ^^^ We conclude that intrauterine growth retardation induced by uteroplacental insufficiency 1 ) affects the hepatic epigenetic characteristics and mRNA of the DUSP 5 and 2 ) increases hepatic insulin receptor substrate 1 phosphorylation at serine 612 in adult rats . . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
In the present study , we investigated the protein levels and phosphorylation status of the insulin receptor and insulin receptor substrates ( IRS 1 , IRS 2 , and IRS 3 ) as well as their association with PI ( 3 ) kinase in the rat adipose tissue of two models of insulin resistance : dexamethasone treatment and aging . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Investigation of insulin signaling revealed that bradykinin enhanced insulin receptor substrate 1 ( IRS 1 ) Tyr phosphorylation , Akt / protein kinase B phosphorylation , and GLUT 4 translocation . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Insulin stimulated a rapid and transient tyrosine phosphorylation of receptor beta subunits ( 95 kDa ) and of IRS 1 in intact Y 79 cells , whereas in vitro studies with enriched membrane glycoproteins resulted in the autophosphorylation of both InsR ( 95 kDa ) and IGF 1 R ( 98k Da ) beta subunits . ^^^
Interacting proteins: P06213 and P35568 Pubmed SVM Score :0.0
Igf1r haploinsufficiency did not affect insulin action and compensatory beta cell growth in insulin resistant mice with combined Insr and Igf1r heterozygous null mutations , resulting in a considerably milder phenotype than combined haploinsufficiency for Insr and its main signaling substrates , Irs 1 and Irs 2 . ^^^