Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation
Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation
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DOI：
10.1038/sj.embor.7400072
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发表时间：
2004-02-01
期刊：
影响因子：
7.7
通讯作者：
Ichijo, H
中科院分区：
文献类型：
--
作者：
Takeda, K;Matsuzawa, A;Ichijo, H
哺乳动物促分裂原活化蛋白（MAP）激酶凋亡信号调节激酶1（ASK 1）是细胞因子和应激诱导的细胞凋亡的关键组分。它还通过p38 MAP激酶激活调节细胞分化和存活。在这里，我们表明，Ca 2+信号调节ASK 1-p38 MAP激酶级联。原代神经元和突触体的膜去极化引起的Ca 2+内流诱导p38的激活，这在来自ASK 1缺陷小鼠的那些中受损。Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）通过磷酸化激活ASK 1。此外，p38激活诱导的组成型活性CaMKII的表达需要内源性ASK 1。因此，ASK 1是CaMKII和p38 MAP激酶之间Ca 2+信号传导的关键中间体。
The mammalian mitogen-activated protein (MAP) kinase kinase kinase apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component in cytokine- and stress-induced apoptosis. It also regulates cell differentiation and survival through p38 MAP kinase activation. Here we show that Ca2+ signalling regulates the ASK1-p38 MAP kinase cascade. Ca2+ influx evoked by membrane depolarization in primary neurons and synaptosomes induced activation of p38, which was impaired in those derived from ASK1-deficient mice. Ca2+/calmodulin-dependent protein kinase type II (CaMKII) activated ASK1 by phosphorylation. Moreover, p38 activation induced by the expression of constitutively active CaMKII required endogenous ASK1. Thus, ASK1 is a critical intermediate of Ca2+ signalling between CaMKII and p38 MAP kinase.