Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
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DOI：
10.1016/s0092-8674(00)81780-8
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发表时间：
1998-10-02
期刊：
影响因子：
64.5
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Stambolic, V;Suzuki, A;Mak, TW
PTEN是一种与蛋白酪氨酸磷酸酶和细胞骨架蛋白张力蛋白具有序列同源性的肿瘤抑制因子。mPTEN突变小鼠胚胎显示出增殖增加的区域。相比之下，mPTEN缺陷的永生化小鼠胚胎成纤维细胞表现出对细胞死亡的敏感性降低，以响应一些凋亡刺激，伴随着组成性升高的活性和蛋白激酶B/Akt的磷酸化，细胞存活的关键调节。外源性PTEN在突变细胞中的表达恢复了它们对激动剂诱导的凋亡的敏感性和正常的PKB/Akt磷酸化模式。此外，PTEN在体外负调节细胞中磷脂酰肌醇（3，4，5）三磷酸的细胞内水平并使其去磷酸化。我们的研究结果表明，PTEN可能发挥其作为一个肿瘤抑制剂的作用，通过负性调节PI 3 ′ K/PKB/Akt信号通路。
PTEN is a tumor suppressor with sequence homology to protein tyrosine phosphatases and the cytoskeletal protein tensin. mPTEN-mutant mouse embryos display regions of increased proliferation. In contrast, mPTEN-deficient immortalized mouse embryonic fibroblasts exhibit decreased sensitivity to cell death in response to a number of apoptotic stimuli, accompanied by constitutively elevated activity and phosphorylation of protein kinase B/Akt, a crucial regulator of cell survival. Expression of exogenous PTEN in mutant cells restores both their sensitivity to agonist-induced apoptosis and normal pattern of PKB/Akt phosphorylation. Furthermore, PTEN negatively regulates intracellular levels of phosphatidylinositol (3,4,5) trisphosphate in cells and dephosphorylates it in vitro. Our results show that PTEN may exert its role as a tumor suppressor by negatively regulating the PI3'K/PKB/Akt signaling pathway.