Pombo C M, Bonventre J V, Molnar A, Kyriakis J, Force T
Cardiac Research Unit of the Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, USA.
EMBO J. 1996 Sep 2;15(17):4537-46.
Mammalian homologs of the yeast protein kinase, Sterile 20 (Ste20), can be divided into two groups based on their regulation and structure. The first group, which includes PAK1, is regulated by Rac and Cdc42Hs, and activators have been identified. In contrast, very little is known about activators, regulatory mechanisms or physiological roles of the other group, which consists of GC kinase and MST1. We have identified a human Ste20-like kinase from the GC kinase group, SOK-1 (Ste20/oxidant stress response kinase-1), which is activated by oxidant stress. The kinase is activated by autophosphorylation and is markedly inhibited by its non-catalytic C-terminal region. SOK-1 is activated 3- to 7-fold by reactive oxygen intermediates, but is not activated by growth factors, alkylating agents, cytokines or environmental stresses including heat shock and osmolar stress. Although these data place SOK-1 on a stress response pathway, SOK-1, unlike GC kinase and PAK1, does not activate either of the stress-activated MAP kinase cascades (p38 and SAPKs). SOK-1 is the first mammalian Ste20-like kinase which is activated by cellular stress, and the activation is relatively specific for oxidant stress. Since SOK-1 does not activate any of the known MAP kinase cascades, its activation defines a novel stress response pathway which is likely to include a unique stress-activated MAP kinase cascade.
酵母蛋白激酶不育20（Ste20）的哺乳动物同源物可根据其调节方式和结构分为两组。第一组包括PAK1，受Rac和Cdc42Hs调节，并且已经鉴定出其激活剂。相比之下，对于由GC激酶和MST1组成的另一组的激活剂、调节机制或生理作用知之甚少。我们从GC激酶组中鉴定出一种人类Ste20样激酶，即SOK-1（Ste20/氧化应激反应激酶-1），它可被氧化应激激活。该激酶通过自身磷酸化被激活，并被其非催化性C末端区域显著抑制。SOK-1可被活性氧中间体激活3至7倍，但不受生长因子、烷化剂、细胞因子或包括热休克和渗透压应激在内的环境应激激活。尽管这些数据表明SOK-1处于应激反应途径中，但与GC激酶和PAK1不同，SOK-1不会激活任何一种应激激活的丝裂原活化蛋白激酶级联反应（p38和SAPKs）。SOK-1是首个被细胞应激激活的哺乳动物Ste20样激酶，并且这种激活对氧化应激具有相对特异性。由于SOK-1不会激活任何已知的丝裂原活化蛋白激酶级联反应，其激活定义了一条新的应激反应途径，该途径可能包括一个独特的应激激活丝裂原活化蛋白激酶级联反应。
