FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma cell line
FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma cell line
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DOI：
10.1074/jbc.274.15.10566
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发表时间：
1999-04-09
影响因子：
4.8
通讯作者：
Kasahara, T
中科院分区：
文献类型：
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作者：
Sonoda, Y;Watanabe, S;Kasahara, T
研究了体外氧化应激对人胶质母细胞瘤细胞系T98G蛋白质磷酸化的影响。过氧化氢(1 MM)刺激后1h可显著诱导粘着斑激酶(FAK)酪氨酸磷酸化和Akt丝氨酸磷酸化。在过氧化氢刺激下，也观察到FAK与磷脂酰肌醇3‘-羟基-激酶(PI-3-Kinase)的结合。当PI3K抑制剂Wortmannin作用于T98G细胞时，PI3K活性和Akt的磷酸化均被抑制，而氧化应激所致的细胞凋亡却被加速。伴随着细胞凋亡，CPP32蛋白活性(caspase-3)水平升高，Bcl2蛋白表达降低，Pax蛋白表达增加。这些结果表明，在从FAR到PI3-激酶的信号转导途径中，Akt促进了细胞的存活。由此可见，在过氧化氢诱导的T98G细胞凋亡中，FAK是PI-3-K-Akt生存通路的上游信号蛋白。
Protein phosphorylation in a human glioblastoma cell line, T98G, was examined after exposure to oxidative stress in vitro. Hydrogen peroxide (1 mM) markedly induced tyrosine phosphorylation of focal adhesion kinase (FAK) and serine phosphorylation of Akt at 1 h after stimulation. Concommitantly, the association of FAK with phosphatidylinositide 3'-OH-kinase (PI 3-kinase) was also observed by the hydrogen peroxide stimulation. When T98G cells were incubated with wortmannin, a PI 3-kinase inhibitor, both PI 3-kinase activity and phosphorylation of Akt were inhibited, whereas apoptosis by oxidative stress was accelerated. Concomitant with apoptosis, elevated level of CPP32 protease activity (caspase-3) was observed, with decreases in Bcl-2 protein and increases in Pax protein. These results suggested that in the signal transduction pathway from FAR to PI 3-kinase, Akt promotes survival. Thus, it became apparent that FAK is the upstream signal protein of the PI 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis in T98G cells.