Inhibition of IL-6 family cytokines by SOCS3.

ABSTRACT: IL-6 a multi-functional cytokine with important effects in both inflammation and haematopoiesis. SOCS3 is the primary inhibitor of IL-6 signalling, interacting with gp130, the common shared chain of the IL-6 family of cytokines, and JAK1, JAK2 and TYK2 to control both the duration of signalling and the biological response. Recent biochemical and structural studies have shown SOCS3 binds to only these three JAKs, all of which are associated with IL-6 signalling, and not JAK3. This specificity is determined by a three residue "GQM" motif in the kinase domain of JAK1, JAK2 and TYK2. SOCS3 binds to JAK and gp130 simultaneously, and inhibits JAK activity in an ATP-independent manner by partially occluding the kinase's substrate binding groove with its kinase inhibitory region. We therefore prop

SUBMITTER: Babon JJ 

PROVIDER: S-EPMC3970923 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature