SOCS3 in Liver Regeneration and Hepatocarcinoma

Regulation of IL-6 signaling by SOCS3. IL-6 signaling leads to activation of gp130 and phosphorylation (represented by purple circles) of STAT3 monomers by Janus kinases (JAKs). STAT3 then homodimerizes and translocates to the nucleus, where it induces transcription of a number of target genes, including Socs3. SOCS are believed to inhibit cytokine signaling by either binding to activated cytokine receptors and/or JAKs, or by targeting receptor complexes for degradation. SOCS3 can bind to JAK and the gp130 receptor at phosphotyrosine 759 (pY⁷⁵⁹) via its kinase inhibitory region (KIR) and Src homology 2 (SH2) domains, respectively, to inhibit JAK-STAT signaling.