Signalling links in the liver: Knitting SOCS with fat and inflammation Geoffrey C. Farrell  Journal of Hepatology  Volume 43, Issue 1, Pages 193-196 (July 2005) DOI: 10.1016/j.jhep.2005.04.004 Copyright © 2005 Terms and Conditions

Fig. 1 Suppressors of cytokine signalling (SOCS) and other molecules which modulate insulin receptor (IR) signalling in liver. Binding of insulin to the IR causes it to undergo autophosphorylation, thereby conferring Src homology. In addition to activating insulin receptor substrates (IRS) 1 and 2, this activates JAK, leading to recruitment and activation of signal transduction and activator of transcription (STAT) molecules—STAT-3, a target of SOCS-3, is illustrated here. PTEN (phosphatase and tension homologue deleted on chromosome 10), PTP (protein tyrosine phosphatase) 1B and SHP (SH domain phosphatase) 2 are among several phosphatases which dephosphorylate phosphatidylinositol-3,4,5-trisphosphate (PI3P), the IR at its Src active site, and IRS, respectively (reviewed in Ref. [5]). These actions reduce activity of the phosphatidylinositol-3,4,5-trisphosphate kinase (PI3K) and downstream activation of Akt. SOCS proteins, especially SOCS-1 and SOCS-3, could act at multiple sites to impair IR signalling, but phosphorylation of insulin receptor signalling proteins (IRS) and blockade of STAT3 activation may be of greatest relevance to effects in liver. SREBP-1c, sterol regulatory element binding protein-1c. [This figure appears in colour on the web]. Journal of Hepatology 2005 43, 193-196DOI: (10.1016/j.jhep.2005.04.004) Copyright © 2005 Terms and Conditions