Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway
Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway
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DOI：
10.1074/jbc.273.32.19929
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发表时间：
1998-08-07
影响因子：
4.8
通讯作者：
Cooper, GM
中科院分区：
文献类型：
--
作者：
Pap, M;Cooper, GM
多种哺乳动物细胞的生长因子依赖性存活依赖于磷脂酰肌醇（PI） 3-激酶及其下游效应蛋白激酶Akt的活化。糖原合成酶激酶3 （GSK-3）先前已被确定为Akt的生理靶点，其被磷酸化抑制，因此我们研究了GSK-3在细胞存活中的作用。过度表达具有催化活性的GSK-3诱导了大鼠1和PC12细胞的凋亡，而显性阴性的GSK-3通过抑制PI 3-激酶来阻止细胞凋亡。因此GSK-3在细胞凋亡调控中起关键作用，是PI 3-激酶/Akt存活信号通路的关键下游靶点。
Growth factor-dependent survival of a variety of mammalian cells is dependent on the activation of phosphatidylinositol (PI) 3-kinase and its downstream effector, the protein kinase Akt. Glycogen synthase kinase-3 (GSK-3) has been previously identified as a physiological target of Akt, which is inhibited by phosphorylation, so we have investigated the role of GSK-3 in cell survival. Overexpression of catalytically active GSK-3 induced apoptosis of both Rat-1 and PC12 cells, whereas dominant-negative GSK-3 prevented apoptosis following inhibition of PI 3-kinase. GSK-3 thus plays a critical role in regulation of apoptosis and represents a key downstream target of the PI 3-kinase/Akt survival signaling pathway.