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dc.contributor.authorLiau, NPD
dc.contributor.authorLaktyushin, A
dc.contributor.authorLucet, IS
dc.contributor.authorMurphy, JM
dc.contributor.authorYao, S
dc.contributor.authorWhitlock, E
dc.contributor.authorCallaghan, K
dc.contributor.authorNicola, NA
dc.contributor.authorKershaw, NJ
dc.contributor.authorBabon, JJ
dc.date.accessioned2020-12-17T03:09:57Z
dc.date.available2020-12-17T03:09:57Z
dc.date.issued2018-04-19
dc.identifierpii: 10.1038/s41467-018-04013-1
dc.identifier.citationLiau, N. P. D., Laktyushin, A., Lucet, I. S., Murphy, J. M., Yao, S., Whitlock, E., Callaghan, K., Nicola, N. A., Kershaw, N. J. & Babon, J. J. (2018). The molecular basis of JAK/STAT inhibition by SOCS1. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-04013-1.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/254772
dc.description.abstractThe SOCS family of proteins are negative-feedback inhibitors of signalling induced by cytokines that act via the JAK/STAT pathway. SOCS proteins can act as ubiquitin ligases by recruiting Cullin5 to ubiquitinate signalling components; however, SOCS1, the most potent member of the family, can also inhibit JAK directly. Here we determine the structural basis of both these modes of inhibition. Due to alterations within the SOCS box domain, SOCS1 has a compromised ability to recruit Cullin5; however, it is a direct, potent and selective inhibitor of JAK catalytic activity. The kinase inhibitory region of SOCS1 targets the substrate binding groove of JAK with high specificity and thereby blocks any subsequent phosphorylation. SOCS1 is a potent inhibitor of the interferon gamma (IFNγ) pathway, however, it does not bind the IFNγ receptor, making its mode-of-action distinct from SOCS3. These findings reveal the mechanism used by SOCS1 to inhibit signalling by inflammatory cytokines.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe molecular basis of JAK/STAT inhibition by SOCS1
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-018-04013-1
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentBio21
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titleNature Communications
melbourne.source.volume9
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1323583
melbourne.contributor.authorLucet, Isabelle
melbourne.contributor.authorBabon, Jeffrey
melbourne.contributor.authorMurphy, James
melbourne.contributor.authorYao, Shenggen
melbourne.contributor.authorWhitlock, Eden
melbourne.contributor.authorNicola, Nicos
melbourne.contributor.authorKershaw, Nadia
melbourne.contributor.authorLiau, Nicholas
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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