Dual effects of suppressor of cytokine signaling (SOCS‐2) on growth hormone signal transduction

Open Access
Publisher Website
Google Scholar
Abstract
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.