Regulation of multiple cytokine signalling pathways by SOCS3 is independent of SOCS2

Abstract

Suppressor of cytokine signalling (SOCS) 3 is an essential regulator of cytokine signalling, and in turn its expression is tightly regulated. Data from overexpression studies in cell lines suggest that SOCS2 regulates SOCS3 protein degradation, by forming a molecular bridge to an E3 ubiquitin-ligase complex. Whether this regulation is relevant in primary cells is unknown. In this study, we utilized Socs2 ^{− / −} mice to examine the role of SOCS2 in modulating SOCS3 expression and degradation, and its impact on interleukin-2 (IL-2) and IL-6 signalling in primary haemopoietic cells. Both biochemical and biological analyses demonstrated unperturbed SOCS3 expression and cytokine signalling in the absence of SOCS2. Our results suggest that SOCS2 is not a physiological regulator of SOCS3 expression and action in primary haemopoietic cells.

Keywords::

• SOCS2
• SOCS3
• IL-6
• IL-2
• STAT
• macrophages
• lymphocytes

Acknowledgements

We are grateful to Janelle Lochland for technical assistance and Jian-Guo Zhang and Sandra Nicholson for invaluable discussion and advice. This work was supported by a grant from the National Institutes of Health (CA022556); Fellowships (CJG, DJH, WSA, NN and AWR), a Program Grant from the National Health and Medical Research Council (NHMRC) of Australia (461291); NHMRC Independent Research Institutes Infrastructure Support Scheme (361646); and Victorian State Government Operational Infrastructure Support grant. HK is a recipient of a Biomedical (Dora Lush) Postgraduate Research Scholarship from the NHMRC.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.