The molecular basis of JAK/STAT inhibition by SOCS1

Nicholas P. D. Liau, Artem Laktyushin, Isabelle S. Lucet, James M. Murphy, Shenggen Yao, Eden Whitlock, Kimberley Callaghan, Nicos A. Nicola, Nadia J. Kershaw () and Jeffrey J. Babon ()
Additional contact information
Nicholas P. D. Liau: 1G Royal Parade
Artem Laktyushin: 1G Royal Parade
Isabelle S. Lucet: 1G Royal Parade
James M. Murphy: 1G Royal Parade
Shenggen Yao: Royal Parade
Eden Whitlock: 1G Royal Parade
Kimberley Callaghan: 1G Royal Parade
Nicos A. Nicola: 1G Royal Parade
Nadia J. Kershaw: 1G Royal Parade
Jeffrey J. Babon: 1G Royal Parade

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract The 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04013-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04013-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04013-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().