Regulation of Janus kinases by SOCS proteins
- Author(s)
- Kershaw, NJ; Murphy, JM; Lucet, IS; Nicola, NA; Babon, JJ;
- Journal Title
- BIOCHEMICAL SOCIETY TRANSACTIONS
- Publication Type
- Journal Article
- Abstract
- JAKs (Janus kinases) are essential mediators of almost all biological signalling events initiated by haemopoietic and immune cytokines. However, aberrant and/or prolonged JAK-induced signalling is detrimental and can give rise to a number of inflammatory and proliferative pathologies. For this reason, the tyrosine kinase activity of the JAKs is carefully regulated at a number of different levels. Primarily, this is achieved by: (i) ensuring that the catalytic domain is 'switched off' under basal conditions, and (ii) inhibiting the activity of JAK after it has been switched on. Whereas the first mode of inhibition is mediated by JAK's own pseudokinase domain as well as the action of phosphatases, the second is achieved by the action of the SOCS (suppressor of cytokine signalling) proteins, negative-feedback inhibitors of JAK-mediated signalling. The present review focuses on the mode of action of SOCS1 and SOCS3, the two most potent JAK inhibitors.
- Publisher
- PORTLAND PRESS LTD
- Keywords
- cytokine signalling; Janus kinase (JAK); signal transducer and activator of transcription (STAT); suppressor of cytokine signalling (SOCS)
- Research Division(s)
- Structural Biology; Cancer And Haematology
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773493/
- Publisher's Version
- https://doi.org/10.1042/BST20130077
- Terms of Use/Rights Notice
- © The Authors Journal compilation © 2013 Biochemical Society
Creation Date: 2013-08-01 12:00:00