Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1
Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1
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DOI：
10.1128/mcb.21.3.893-901.2001
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发表时间：
2001-02-01
影响因子：
5.3
通讯作者：
Chao, MV
中科院分区：
文献类型：
--
作者：
Kim, AH;Khursigara, G;Chao, MV
Akt家族的丝氨酸/苏氨酸定向激酶部分通过磷酸化和抑制诱导死亡的蛋白来促进细胞存活。在这里，我们描述了Akt和凋亡信号调节激酶1 （ASK1）之间的一种新的功能相互作用，ASK1是一种丝裂原激活的蛋白激酶。在293细胞中，Akt通过磷酸化ASK1丝氨酸83的Akt位点，降低氧化应激和过度表达刺激下的ASK1激酶活性。磷酸肌肽3-激酶(PI3-K)/Akt通路的激活也抑制了L929细胞中血清剥夺诱导的内源性ASK1的活性。共免疫沉淀法检测细胞中Akt和ASK1的关联。Akt磷酸化抑制ask1介导的c-Jun n -末端激酶和激活转录因子2在完整细胞中的活性。最后，PI3-K/Akt通路的激活以依赖ASK1丝氨酸83磷酸化的方式减少ASK1诱导的细胞凋亡。这些结果提供了Akt和应激激活激酶家族之间的第一个直接联系。
The Akt family of serine/threonine-directed kinases promotes cellular survival in part by phosphorylating and inhibiting death-inducing proteins. Here we describe a novel functional interaction between Akt and apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase. Akt decreased ASK1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus Akt site at serine 83 of ASK1. Activation of the phosphoinositide 3-kinase (PI3-K)/Akt pathway also inhibited the serum deprivation-induced activity of endogenous ASK1 in L929 cells. An association between Akt and ASK1 was detected in cells by coimmunoprecipitation. Phosphorylation by Akt inhibited ASK1-mediated c-Jun N-terminal kinase and activating transcription factor 2 activities in intact cells. Finally, activation of the PI3-K/Akt pathway reduced apoptosis induced by ASK1 in a manner dependent on phosphorylation of serine 83 of ASK1. These results provide the first direct link between Akt and the family of stress-activated kinases.