Inhibition of IL-6 family cytokines by SOCS3: characterizing the mode of inhibition and the basis of its specificity

Abstract

Maintenance of the haematopoietic and immune systems is largely controlled by the secretion of cytokines. Cytokine exposure initiates an intracellular signalling cascade that is driven by activation of a family of receptor-bound tyrosine kinases known as the JAKs (Janus Kinases). Under physiological conditions, JAK activation and signalling is tightly regulated, in particular by the SOCS (Suppressors of Cytokine Signalling) family of proteins. IL-6 is a multi-functional cytokine with important effects in both inflammation and haematopoiesis and SOCS3 is the primary inhibitor of IL-6 family signalling. Using structural and biochemical techniques, we have determined the molecular basis for the..