Interaction of Suppressor of Cytokine Signalling 3 with Cavin-1 Links SOCS3 Function and Cavin-1 Stability

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jan 14

PMID 29330478

Citations 17

Authors

Jamie J L Williams

Nasser Alotaiq

William Mullen

Richard Burchmore

Libin Liu

George S Baillie

Fred Schaper

Paul F Pilch

Timothy M Palmer

Affiliations

Soon will be listed here.

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.

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