Journal article

Suppressor of Cytokine Signaling (SOCS) 5 Utilises Distinct Domains for Regulation of JAK1 and Interaction with the Adaptor Protein Shc-1

Edmond M Linossi, Indu R Chandrashekaran, Tatiana B Kolesnik, James M Murphy, Andrew I Webb, Tracy A Willson, Lukasz Kedzierski, Alex N Bullock, Jeffrey J Babon, Raymond S Norton, Nicos A Nicola, Sandra E Nicholson

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2013

Abstract

Suppressor of Cytokine Signaling (SOCS)5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF) signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR). Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can direc..

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Grants

Awarded by National Health and Medical Research Council (NHMRC), Australia


Awarded by NHMRC IRIISS grant


Awarded by ARC Future Fellowships


Awarded by Structural Genomics Consortium


Awarded by Wellcome Trust


Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported in part by the National Health and Medical Research Council (NHMRC), Australia (Program grants #461219 and #487922, Project grant #1023559), as well as an NHMRC IRIISS grant 361646 and a Victorian State Government Operational Infrastructure Scheme grant. SEN, RSN and NAN are supported by NHMRC fellowships, JJB and JMM by ARC Future Fellowships (FT110100169 and FT100100100) and EML by an Australian Postgraduate Award. ANB was supported by the Structural Genomics Consortium, a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, Genome Canada, GlaxoSmithKline, Lilly Canada, the Novartis Research Foundation, Pfizer, Takeda, AbbVie, the Canada Foundation for Innovation, the Ontario Ministry of Economic Development and Innovation, and the Wellcome Trust [092809/Z/10/Z]. This work was also supported in part by the National Institutes of Health (RO1 CA22556-26). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.