Yes / 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. / This work was supported by project grants to T.M.P. from the Chief Scientist Office (ETM/226), British Heart Foundation (PG12/1/ 29276, PG 14/32/30812), and a National Health Service Greater Glasgow and Clyde Research Endowment Fund (2011REFCH08). P.F.P. was supported by the National Institutes of Health grant DK097708. J.J.L.W. was supported by a doctoral training studentship from the Biotechnology and Biological Sciences Research Council Doctoral Training Programme in Biochemistry and Molecular Biology at the University of Glasgow (BB/F016735/1). N.A. was supported by a Saudi Government PhD Scholarship. This work was also supported in part by equipment grants to T.M.P. from Diabetes UK (BDA 11/0004309) and Alzheimer’s Research UK (ARUK-EG2016A-3).
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/14661 |
| Date | 12 January 2018 |
| Creators | Williams, Jamie J.L., Alotaiq, N., Mullen, W., Burchmore, R., Liu, L., Baillie, G.S., Schaper, F., Pilch, P.F., Palmer, Timothy M. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ . |
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