| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| 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: O14543 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 . ^^^ By contrast , SOCS 3 binding required tyrosine phosphorylated GHR membrane proximal sequences , SOCS 1 binding was tyrosine phosphorylation independent , and SOCS 6 did not bind the GHR fusion proteins at all . ^^^ 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: O14543 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 ) . ^^^ 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 . ^^^ |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| 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: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| The expression of IGF 1 , GHR , SOCS 3 and beta actin mRNA in the liver was detected by RT PCR and the GH levels were measured by radioimmunoassay , the levels of TNF alpha and IL 6 were detected by ELISA . ^^^ The liver GHR mRNA expression was obviously down regulated after TNF alpha 4 injection and had a 40 % decrease at 8h , but the liver SOCS 3 mRNA expression was the 4 . 94 times up regulation occurred at 40 min after IL 6 injection . ^^^ CONCLUSION : The growth hormone insensitivity could be induced by LPS injection , which was associated with down regulated GHR mRNA expression at receptor level and with up regulated SOCS 3 mRNA expression at post receptor level . ^^^ |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| 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: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| In contrast , no tyrosine phosphorylated adipocyte proteins were recovered after immunoprecipitation with alpha SOCS 3 , although coprecipitation of GHR with SOCS 3 was readily detected in extracts of 3T3 F442A fibroblasts . ^^^ |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| Liver expression of IGF 1 , GHR and SOCS 3 mRNA was detected by RT PCR , the levels of growth hormone ( GH ) were measured by radioimmunoassay , and the levels of TNF alpha and IL 6 were detected by ELISA . ^^^ The higher LPS dosage induced marked GHR mRNA down regulation and marked SOCS 3 mRNA up regulation . ^^^ Liver GHR mRNA expression was obviously down regulated after TNF alpha i . v . injection , but for IL 6 , it mainly up regulated the liver SOCS 3 mRNA expression . ^^^ CONCLUSION : The growth hormone insensitivity could be induced by LPS injection , which might be associated with down regulated GHR mRNA expression and up regulated SOCS 3 mRNA expression . ^^^ |
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| Interacting proteins: O14543 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 . ^^^ Our data suggest that GH induces refractoriness to the insulin like effects in a negative feedback manner by inhibiting GH induced GHR / Jak2 / IRS 1 / IRS 2 phosphorylation through upregulation of SOCS 3 , which almost completely blocks Jak 2 activation . . ^^^ |
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| Interacting proteins: O14543 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: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O14543 and P10912 |
Pubmed |
SVM Score :0.0 |
| NA |
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