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Nat Commun. 2018 Jan 12;9(1):168. doi: 10.1038/s41467-017-02585-y.

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

Author information

1
School of Pharmacy and Medical Sciences, University of Bradford, Bradford, BD7 1DP, UK. j.j.l.williams@bradford.ac.uk.
2
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
3
Polyomics Facility, University of Glasgow, Glasgow, G12 8QQ, UK.
4
Departments of Biochemistry and Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.
5
Department of Systems Biology, Institute for Biology, Otto-von-Guericke-University Magdeburg, 39106, Magdeburg, Germany.
6
School of Pharmacy and Medical Sciences, University of Bradford, Bradford, BD7 1DP, UK. T.Palmer1@bradford.ac.uk.

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.

PMID:
29330478
PMCID:
PMC5766592
DOI:
10.1038/s41467-017-02585-y
[Indexed for MEDLINE]
Free PMC Article

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