Stambolic V, Suzuki A, de la Pompa J L, Brothers G M, Mirtsos C, Sasaki T, Ruland J, Penninger J M, Siderovski D P, Mak T W
Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Cell. 1998 Oct 2;95(1):29-39. doi: 10.1016/s0092-8674(00)81780-8.
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.
PTEN是一种肿瘤抑制因子，与蛋白质酪氨酸磷酸酶和细胞骨架蛋白张力蛋白具有序列同源性。mPTEN突变的小鼠胚胎显示出增殖增加的区域。相反，mPTEN缺陷的永生化小鼠胚胎成纤维细胞对多种凋亡刺激引起的细胞死亡敏感性降低，同时蛋白激酶B/Akt（细胞存活的关键调节因子）的活性和磷酸化持续升高。在突变细胞中表达外源性PTEN可恢复其对激动剂诱导的凋亡的敏感性以及PKB/Akt磷酸化的正常模式。此外，PTEN在细胞中负调节磷脂酰肌醇（3,4,5）三磷酸的细胞内水平，并在体外使其去磷酸化。我们的结果表明，PTEN可能通过负调节PI3'K/PKB/Akt信号通路发挥其作为肿瘤抑制因子的作用。
