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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, N. Mullen, W. Burchmore, R. Liu, L. Baillie, G.S. Schaper, F. Pilch, P.F. Palmer, Timothy M.
Williams, Jamie J.L.
Alotaiq, N.
Mullen, W.
Burchmore, R.
Liu, L.
Baillie, G.S.
Schaper, F.
Pilch, P.F.
Palmer, Timothy M.
Publication Date
2018-01
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© The Author(s) 2018.
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openAccess
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2017-12-11
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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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Published version
Citation
Williams JJL, Alotaiq N, Mullen W et al (2018) Interaction of suppressor of cytokine
signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nature Communications. 9:
168.
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Article