Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Biochem Soc Trans. 2013 Aug;41(4):1042-7. doi: 10.1042/BST20130077.
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.
JAKs（Janus kinases）是由造血细胞因子和免疫细胞因子引发的几乎所有生物信号事件的必需介质。然而，异常和/或延长的 JAK 诱导的信号是有害的，并可能导致许多炎症和增殖性病理。出于这个原因，JAK 的酪氨酸激酶活性在许多不同的水平上受到仔细的调节。主要通过以下两种方式实现：（i）确保在基础条件下，催化结构域处于“关闭”状态；（ii）在 JAK 被激活后抑制其活性。第一种抑制方式是由 JAK 自身的假激酶结构域以及磷酸酶的作用介导的，而第二种抑制方式是由 SOCS（细胞因子信号转导抑制因子）蛋白，JAK 介导的信号的负反馈抑制剂来实现的。本综述重点介绍了 SOCS1 和 SOCS3 的作用模式，它们是两种最有效的 JAK 抑制剂。
