PMID:9778245

Citation	Stambolic, V, Suzuki, A, de la Pompa, JL, Brothers, GM, Mirtsos, C, Sasaki, T, Ruland, J, Penninger, JM, Siderovski, DP and Mak, TW (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29-39
Abstract	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.
Links	PubMed
Keywords	Animals; Apoptosis; Cell Division; Cell Survival; Cells, Cultured; Female; Fibroblasts/cytology; Genes, Tumor Suppressor; Mice; Mutagenesis; PTEN Phosphohydrolase; Phosphatidylinositol Phosphates/metabolism; Phosphoric Monoester Hydrolases; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/physiology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt; Substrate Specificity; Tumor Suppressor Proteins
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