Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction.
A family of suppressors of cytokine signaling (SOCS) has recently been identified of which two members have been shown to block growth hormone (GH) signaling. Dose-response experiments were conducted in 293 cells and SOCS-1 and SOCS-3 were shown to inhibit the transcriptional activation of a GH-responsive element and suppressed Jak2 tyrosine kinase activity. SOCS-2 had two opposite effects: at low concentrations it inhibited GH-induced STAT5-dependent gene transcription, but restoration of GH signaling was observed at higher concentrations. In cotransfection studies, SOCS-2 was able to block the inhibitory effect of SOCS-1 but not that of SOCS-3 on GH signaling. These findings suggest that a major function for SOCS-2 is to restore the sensitivity to GH by overcoming the initial inhibitory effects of other endogenous SOCS molecules.
Favre
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H
INSERM Unité 344-Endocrinologie Moléculaire, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Benhamou
A
A
Finidori
J
J
Kelly
P A
PA
Edery
M
M
D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D007668:Kidney / Q000166:cytology; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D020218:Response Elements; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D019382:Human Growth Hormone; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2