Mechanism of p38 MAP kinase activation in vivo
Mechanism of p38 MAP kinase activation in vivo
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DOI：
10.1101/gad.1107303
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发表时间：
2003-08-15
影响因子：
10.5
通讯作者：
Davis, RJ
中科院分区：
文献类型：
--
作者：
Brancho, D;Tanaka, N;Davis, RJ
p38丝裂原活化蛋白激酶（MAPK）在体外被三种不同的蛋白激酶激活：MKK3，MKK4和MKK6。为了研究这些蛋白激酶在体内p38 MAP激酶激活机制中的相对作用，我们研究了小鼠Mkk3、Mkk4和Mkk6基因的破坏对p38 MAPK信号通路的影响。我们发现，MKK3和MKK6是必不可少的肿瘤坏死因子刺激的p38 MAPK激活。相反，紫外线辐射刺激的p38 MAPK活化由MKK3、MKK4和MKK6介导。突变细胞中p38 MAPK活化的丧失与生长停滞缺陷和肿瘤发生增加相关。这些数据表明，p38 MAPK是由三种不同的蛋白激酶响应于细胞因子和暴露于环境应激的协调和选择性作用调节的。
The p38 mitogen-activated protein kinase (MAPK) is activated in vitro by three different protein kinases: MKK3, MKK4, and MKK6. To examine the relative roles of these protein kinases in the mechanism of p38 MAP kinase activation in vivo, we examined the effect of disruption of the murine Mkk3, Mkk4, and Mkk6 genes on the p38 MAPK signaling pathway. We show that MKK3 and MKK6 are essential for tumor necrosis factor-stimulated p38 MAPK activation. In contrast, ultraviolet radiation-stimulated p38 MAPK activation was mediated by MKK3, MKK4, and MKK6. Loss of p38 MAPK activation in the mutant cells was associated with defects in growth arrest and increased tumorigenesis. These data indicate that p38 MAPK is regulated by the coordinated and selective actions of three different protein kinases in response to cytokines and exposure to environmental stress.