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.

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.

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), Article 168. https://doi.org/10.1038/s41467-017-02585-y

• Journal Article Type: Article
• Acceptance Date: Dec 11, 2017
• Online Publication Date: Jan 12, 2018
• Publication Date: Jan 12, 2018
• Deposit Date: Oct 30, 2018
• Publicly Available Date: Oct 30, 2018
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 168
• DOI: https://doi.org/10.1038/s41467-017-02585-y
• Keywords: Growth factor signalling; Interleukins
• Public URL: https://hull-repository.worktribe.com/output/1137035
• Publisher URL: https://www.nature.com/articles/s41467-017-02585-y