Journal article

Inhibition of IL-6 family cytokines by SOCS3

Jeffrey J Babon, Leila N Varghese, Nicos A Nicola

Seminars in Immunology | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2014

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 ..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by U.S. National Institutes of Health


Awarded by NHMRC Independent Research Institutes Infrastructure Support Scheme


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

The original research described in this review was supported by the National Health and Medical Research Council of Australia (programme grant nos. 461219 and 487922, 1011804), the U.S. National Institutes of Health (grant no. CA22556), the Victorian State Government Operational Infrastructure Support Grant, and the NHMRC Independent Research Institutes Infrastructure Support Scheme (361646). N.A.N. acknowledges fellowship support from the National Health and Medical Research Council, L.N.V. from the Leukaemia Foundation of Australia and the Australian Stem Cell Centre and J.J.B. from the Australian Research Council.