| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.63184533 |
| These findings demonstrate the interaction of CIS with the GHR in vivo and suggest that CIS may enhance degradation of the receptor by a proteasomal pathway . . 0.63184533^^^ Interaction of GHR with CIS peaked between 2 and 10 min after adipocytes were treated with GH , when tyrosine phosphorylation of the GHR was maximal . 0.50292803^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| The biological activities of CFP SOCS 2 and YFP SOCS 2 were also assayed using GST GHR binding assay . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| SOCS 2 binds to the GH receptor and inhibits GH signaling , including attenuation of STAT 5 activation . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| SOCS 1 , SOCS 2 , SOCS 3 , and CIS each strongly inhibited the GH receptor ( GHR ) dependent tyrosine phosphorylation of JAK 2 seen at low levels of transfected JAK 2 ; however , only SOCS 1 strongly inhibited the GHR independent tyrosine phosphorylation of JAK 2 seen at higher JAK 2 levels . ^^^ CIS and SOCS 2 bound to fusions containing as few as 80 COOH terminal GHR residues , provided the fusion protein was tyrosine phosphorylated . ^^^ Mutation of GHR ' s membrane proximal tyrosine residues 333 and 338 to phenylalanine suppressed the inhibition by SOCS 3 , but not by CIS , of GH signaling to STAT5b . ^^^ SOCS / CIS proteins can thus inhibit GH signaling to STAT5b by three distinct mechanisms , distinguished by their molecular targets within the GHR JAK 2 signaling complex , as exemplified by SOCS 1 ( direct JAK 2 kinase inhibition ) , SOCS 3 ( inhibition of JAK 2 signaling via membrane proximal GHR tyrosines 333 and 338 ) , and CIS and SOCS 2 ( inhibition via membrane distal tyrosine ( s ) ) . . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| Growth hormone ( GH ) inducible suppressors of cytokine signaling ( SOCS / CIS proteins ) inhibit GH receptor ( GHR ) signaling to STAT5b via phosphotyrosine dependent binding interactions with the tyrosine kinase JAK 2 ( SOCS 1 ) and / or the cytoplasmic tail of GHR ( CIS and SOCS 3 ) . ^^^ Presently , we investigate the mechanism of CIS inhibition and CIS ' s role in down regulating GHR JAK 2 signaling to STAT5b in cells exposed to GH continuously . ^^^ CIS is shown to inhibit GHR JAK 2 signaling by two distinct mechanisms : by a partial inhibition that is decreased at elevated STAT5b levels and may involve competition between CIS and STAT5b for common GHR cytoplasmic tail phosphotyrosine binding sites ; and by a time dependent inhibition , not seen with SOCS 1 or SOCS 3 , that involves proteasome action . ^^^ Proteasome dependent degradation of CIS , most likely in the form of a ( GHR JAK 2 ) CIS complex , is therefore proposed to be an important step in the time dependent CIS inhibition mechanism . ^^^ Finally , the down regulation of GHR JAK 2 signaling to STAT5b seen in continuous GH treated cells could be prevented by treatment of cells with the proteasome inhibitor MG 132 or by expression of CIS R107K , a selective , dominant negative inhibitor of CIS activity . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| Here , we have investigated the impact of nutrition and GH treatment on GH receptor , SOCS 1 , SOCS 2 , SOCS 3 and cytokine inducible SH 2 containing protein ( CIS ) hepatic mRNA expression in a rat model of sepsis , caecal ligation and puncture ( CLP ) . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| LPS administration significantly reduced murine hepatic GHR expression , as well as Sp 1 and Sp 3 binding to GHR promoter cis elements . ^^^ TNF alpha treatment of BNL CL . 2 mouse liver cells reduced Sp 1 and Sp 3 binding to a GHR promoter cis element and downregulated activity of a GHR promoter driven luciferase reporter . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| GH induced the expression of liver Igf 1 mRNA in hypophysectomized male wild type , but not in hypophysectomized male Stat5b ( / ) mice , although the Stat5b ( / ) mice exhibit both normal liver GH receptor expression and strong GH induction of Cytokine inducible SH 2 protein ( Cis ) , which is believed to contribute to the down regulation of GH induced liver STAT5b signaling . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| This acute effect of endotoxin corresponded temporally with transient induction of suppressor of cytokine signaling ( SOCS ) 3 , cytokine inducible SH 2 containing protein ( CIS ) , phosphoenolpyruvate carboxykinase ( PEPCK ) , and insulin like growth factor binding protein ( IGFBP ) 1 and suppression of GH receptor ( GHR ) . ^^^ The inductive effect of sustained endotoxemia relative to pair fed controls could not be explained by differences in expression of GHR , SOCS 3 , or CIS but coincided with normalized PEPCK and IGFBP 1 levels , suggesting better hepatic insulin sensitivity in these animals . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| We have reported that TNF alpha suppresses hepatic GH receptor ( GHR ) gene expression , whereas the cytokine inducible SH 2 containing protein 1 ( Cis ) / suppressors of cytokine signaling ( Socs ) genes are upregulated by TNF alpha and IL 6 and inhibit GH activation of STAT 5 . ^^^ STAT 5 , STAT 3 , GHR , Socs 1 3 , and Cis phosphorylation and abundance were assessed by using immunoblots , EMSA , and / or real time RT PCR . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| We analyzed the promoter region of the dominant transcript ( L 2 ) of the murine GHR to determine that a cis element , L2C1 , interacts with transcription factors NF Y , BTEB 1 , and HMG Y / I . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| With overexpression of GHR , Jak 2 and IRS 1 along with each of these SOCS proteins in human A 293 cells , we could demonstrate that both SOCS 1 and SOCS 3 completely inhibited the GH stimulated tyrosine phosphorylation of IRS 1 , whereas SOCS 2 and CIS did not . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| This could account for the inhibition of STAT 5 activation , because CIS competes with STAT 5 for GH receptor docking sites . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| GHR expression was reduced in BDL mice ; in liver , this was associated with reduced Sp 3 binding to a GHR gene promoter cis element . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| The cytokine inducible SH 2 domain containing protein CIS inhibits signaling from the growth hormone ( GH ) receptor ( GHR ) to STAT5b by a proteasome dependent mechanism . ^^^ Here , we used the GH responsive rat liver cell line CWSV 1 to investigate the role of CIS and the proteasome in GH induced GHR internalization . ^^^ The internalization of GH and GHR was inhibited by CIS R107K , a dominant negative SH 2 domain mutant of CIS , and by the proteasome inhibitors MG 132 and epoxomicin , which prolong GHR signaling to STAT5b . ^^^ Given the established specificity of CIS R107K for blocking the GHR signaling inhibitory actions of CIS , but not those of other SOCS / CIS family members , these findings implicate CIS and the proteasome in the control of GHR internalization following receptor activation and suggest that CIS dependent receptor internalization is a prerequisite for efficient termination of GHR signaling . . ^^^ Role of the cytokine induced SH 2 domain containing protein CIS in growth hormone receptor internalization . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| To that end , we compared : ( a ) the expression of GHR and PRLR mRNAs in 3T3 L 1 preadipocytes during the course of adipocyte differentiation ; ( b ) the induction of STAT 5 activity by GH and PRL during adipogenesis ; and ( c ) the acute effects of GH and PRL on the suppressors of cytokine signaling ( SOCS 1 3 and cytokine inducible SH 2 domain containing protein CIS ) and IGF 1 . ^^^ Our findings reveal disparities in the expression of PRLR and GHR during adipocyte development and differential effects of the hormones on STAT 5 , the SOCS proteins , CIS , and IGF 1 . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| In this study we have investigated the role of suppressor of cytokine signaling ( SOCS ) proteins in GH receptor mediated signaling . ^^^ SOCS 1 inhibited the tyrosine kinase activity of Janus kinase 2 ( JAK 2 ) directly , while SOCS 3 only inhibited JAK 2 when stimulated by the GH receptor . ^^^ All four SOCS proteins were able to bind to a tyrosine phosphorylated glutathione S transferase GH receptor fusion protein , and SOCS 3 required the same 46 C terminal amino acids for GH receptor binding as it did for inhibition of GH mediated transcription and STAT 5 activation . ^^^ These data suggest that SOCS 1 and 3 can suppress GH induced transcriptional activity , presumably by inhibiting the kinase activity of JAK 2 either directly in the case of SOCS 1 or via binding to the tyrosine phosphorylated GH receptor in the case of SOCS 3 . . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| Activation of the GH receptor system is relatively transient , with several mechanisms being involved in down regulation : internalization and degradation of the receptor and recruitment of phosphatases or specific inhibitors of the Jak Stat pathway , the suppressors of cytokine signalling ( SOCS ) proteins . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| The effects of continuous high GH levels on GH signal transduction through the GH receptor ( GHR ) / Janus kinase 2 ( JAK 2 ) / signal transducer and activator of transcription 5 ( STAT 5 ) pathway as well as the desensitization of this pathway by suppressors of cytokine signaling ( SOCS ) were studied in transgenic mice overexpressing GHRH . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| The liver expression of insulin like growth factor 1 ( IGF 1 ) , GH receptor ( GHR ) , and suppresor of cytokine signaling ( SOCS ) 3 mRNA were detected by reverse transcriptase polymerase cha in reaction , the GH levels were measured by radioimmunoassay , the levels of tumor necrosis factor alpha ( TNF alpha ) and interleukin 6 ( IL 6 ) were detected by enzyme linked immunosorbent assay . ^^^ Liver GHR mRNA expression was predominantly down regulated after LPS injection ; although SOCS 3 mRNA was weakly expressed in control rats , it was strongly up regulated in endotoxemic rats . ^^^ Two different LPS dosages ( 7 . 5 mg / kg and 5 . 0 mg / kg ) produced the same down regulation of IGF 1 mRNA expression , however , the higher LPS dosage induced more GHR mRNA down regulation and more SOCS 3 mRNA up regulation . ^^^ CONCLUSION : The mechanism of growth hormone insensitivity induced by endotoxin was associated with down regulated GHR mRNA expression at receptor level and up regulated SOCS 3 mRNA expression at post receptor level . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| The overexpressed SOCS 2 was found to bind to endogenous GH receptors in a number of mouse organs , while phosphopeptide binding studies with recombinant SOCS 2 defined phosphorylated tyrosine 595 on the GH receptor as the site of interaction . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| Growth hormone receptor ( GHR ) , IGF 1 and SOCS 3 mRNA expression was measured in the liver of rats fed with a low protein diet and with GH stimulation . ^^^ Protein diet restriction significantly diminished GHR mRNA and receptor binding sites ( p < 0 . 05 ) , but caused a highly increased SOCS 3 gene expression . ^^^ Growth hormone receptor ( GHR ) , IGF 1 and SOCS 3 mRNA expression was measured in the liver of rats fed with a low protein diet and with GH stimulation . ^^^ |
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| Interacting proteins: Q9NSE2 and P10912 |
Pubmed |
SVM Score :0.0 |
| The negative regulation of STATs seems to be exerted at the GH receptor ( GHR ) / Janus Kinase ( JAK ) complex and involves two main mechanisms : ( 1 ) the GH induced ubiquitination / internalization of GHR and ( 2 ) the action of SOCS proteins . ^^^ We conclude that the integrity of the actin cytoskeleton network plays an essential role in the negative regulation of GHR / JAK2 / STAT5 signaling pathway by facilitating the GHR ubiquitination / degradation through mechanisms acting downstream SOCS . . ^^^ |
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