title: Regulation of Janus kinases by SOCS proteins.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Nadia J
authors.initials: NJ
authors.lastname: Kershaw
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
authors.forename: Isabelle S
authors.initials: IS
authors.lastname: Lucet
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Nicola
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Babon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D053612:Janus Kinases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases