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, H., Benhamou, A., Finidori, J., Kelly, P. A., & Edery, M. (1999). Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction. FEBS Letters, 453(1–2), 63–66. https://doi.org/10.1016/S0014-5793(99)00681-X