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Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability

Williams, Jamie J.L.; Alotaiq, Nasser; Mullen, William; Burchmore, Richard; Liu, Libin; Baillie, George S.; Schaper, Fred; Pilch, Paul F.; Palmer, Timothy M.

Authors

Jamie J.L. Williams

Nasser Alotaiq

William Mullen

Richard Burchmore

Libin Liu

George S. Baillie

Fred Schaper

Paul F. Pilch

Timothy M. Palmer



Abstract

Effective suppression of JAK–STAT signalling by the inducible inhibitor “suppressor of cytokine signalling 3” (SOCS3) is essential for limiting signalling from cytokine receptors. Here we show that cavin-1, a component of caveolae, is a functionally significant SOCS3-interacting protein. Biochemical and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins, thereby reducing caveola abundance in endothelial cells. Moreover, the interaction of cavin-1 and SOCS3 is essential for SOCS3 function, as loss of cavin-1 enhances cytokine-stimulated STAT3 phosphorylation and abolishes SOCS3-dependent inhibition of IL-6 signalling by cyclic AMP. Together, these findings reveal a new functionally important mechanism linking SOCS3-mediated inhibition of cytokine signalling to localisation at the plasma membrane via interaction with and stabilisation of cavin-1.

Journal Article Type Article
Publication Date Jan 12, 2018
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Article Number 168
APA6 Citation Williams, J. J., Alotaiq, N., Mullen, W., Burchmore, R., Liu, L., Baillie, G. S., …Palmer, T. M. (2018). Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nature communications, 9(1), doi:10.1038/s41467-017-02585-y
DOI https://doi.org/10.1038/s41467-017-02585-y
Keywords Growth factor signalling; Interleukins
Publisher URL https://www.nature.com/articles/s41467-017-02585-y

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© The Author(s) 2018



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