p38α mitogen-activated protein kinase sensitizes cells to apoptosis induced by different stimuli
p38α mitogen-activated protein kinase sensitizes cells to apoptosis induced by different stimuli
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DOI：
10.1091/mbc.e03-08-0592
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发表时间：
2004-02-01
影响因子：
3.3
通讯作者：
Nebreda, AR
中科院分区：
文献类型：
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作者：
Porras, A;Zuluaga, S;Nebreda, AR
p38α丝裂原活化蛋白（MAP）激酶是一种广泛表达的信号分子，参与细胞对应激反应的调节，并控制多种细胞类型的增殖和存活。我们使用p38alpha敲除小鼠的细胞系来研究该信号通路在细胞凋亡调控中的作用。在这里，我们发现缺乏p38 α的心肌细胞和成纤维细胞对不同刺激诱导的细胞凋亡更有抵抗力。p38α缺陷细胞的凋亡减少与线粒体促凋亡蛋白Bax和凋亡诱导受体Fas/CD-95的表达减少有关。缺乏p38 α的细胞也会增加细胞外信号调节激酶（ERKs） MAP激酶的活性，这种生存途径的上调似乎至少部分地导致了p38 α缺失时细胞凋亡水平的降低。细胞外信号调节激酶MAP激酶途径介导Ser-727上转录因子STAT3的磷酸化，可能导致p38α -/-细胞中Bax和Fas的表达降低。因此，p38alpha似乎通过上调促凋亡蛋白和下调存活途径使细胞对凋亡敏感。
p38alpha mitogen-activated protein (MAP) kinase is a broadly expressed signaling molecule that participates in the regulation of cellular responses to stress as well as in the control of proliferation and survival of many cell types. We have used cell lines derived from p38alpha knockout mice to study the role of this signaling pathway in the regulation of apoptosis. Here, we show that cardiomyocytes and fibroblasts lacking p38alpha are more resistant to apoptosis induced by different stimuli. The reduced apoptosis of p38alpha-deficient cells correlates with decreased expression of the mitochondrial proapoptotic protein Bax and the apoptosis-inducing receptor Fas/CD-95. Cells lacking p38alpha also have increased extracellular signal-regulated kinase (ERKs) MAP kinase activity, and the up-regulation of this survival pathway seems to be at least partially responsible for the reduced levels of apoptosis in the absence of p38alpha. Phosphorylation of the transcription factor STAT3 on Ser-727, mediated by the extracellular signal-regulated kinase MAP kinase pathway, may contribute to the decrease in both Bax and Fas expression in p38alpha-/- cells. Thus, p38alpha seems to sensitize cells to apoptosis via both up-regulation of proapoptotic proteins and down-regulation of survival pathways.