The suppressors of cytokine signalling (SOCS)
- Author(s)
- Kile, BT; Alexander, WS;
- Details
- Publication Year 2001-10,Volume 58,Issue #11,Page 1627-1635
- Journal Title
- CELLULAR AND MOLECULAR LIFE SCIENCES
- Publication Type
- Journal Article
- Abstract
- Members of the SOCS (suppressor of cytokine signalling) family of proteins play key roles in the negative regulation of cytokine signal transduction. A series of elegant biochemical and molecular biological studies has revealed that these proteins act in a negative feedback loop, inhibiting the cytokine-activated Janus kinase/signal transducers and activators of transcription (JAK/ STAT) signalling pathway to modulate cellular responses. Although structurally related, the precise mechanisms of SOCS-1, SOCS-3 and cytokine-inducible SH2-containing protein (CIS) action vary. Direct interaction of SOCS SH2 domains with the JAK kinases or cytokine receptors allows their recruitment to the signalling complex, where they inhibit JAK catalytic activity or block access of the STATs to receptor binding sites. The defining feature of the family, the C-terminal SOCS box domain, appears dispensable for these actions but is likely to play a key role in negative regulation of signalling by targeting molecules associated with the SOCS proteins for degradation. The relevance of SOCS-mediated regulation of cytokine responses has been brought into sharp focus by the dramatic phenotypes of mice lacking these regulators. Indispensable roles for members of this family have been identified in the regulation of interferon gamma, growth hormone and erythropoietin, and the absence of SOCS-1 or SOCS-3 is lethal in mice.
- Publisher
- BIRKHAUSER VERLAG AG
- Keywords
- UBIQUITIN-LIGASE COMPLEX; MICE LACKING SUPPRESSOR; INDUCED STAT INHIBITOR; INDUCIBLE SH2 PROTEIN; F-BOX PROTEINS; SIGNALING PROTEINS; TRANSGENIC MICE; ELONGIN-B; IFN-GAMMA; T-CELLS
- Publisher's Version
- https://doi.org/10.1007/PL00000801
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-10-01 12:00:00