Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN

✍ Scribed by Vuk Stambolic; Akira Suzuki; José Luis de la Pompa; Greg M Brothers; Christine Mirtsos; Takehiko Sasaki; Jurgen Ruland; Josef M Penninger; David P Siderovski; Tak W Mak

• Book ID: 117268523
• Publisher: Elsevier Science
• Year: 1998
• Tongue: English
• Weight: 998 KB
• Volume: 95
• Category: Article
• ISSN: 0092-8674
• DOI: 10.1016/s0092-8674(00)81780-8

✦ Synopsis

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.