Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN

Vuk Stambolic, Akira Suzuki, José Lois De la Pompa, Greg M. Brothers, Christine Mirtsos, Takehiko Sasaki, Jurgen Ruland, Josef M. Penninger, David P. Siderovski, Tak W. Mak

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1940 Scopus citations

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 Pl3'K/PKB/Akt signaling pathway.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalCell
Volume95
Issue number1
DOIs
StatePublished - 2 Oct 1998

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    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. (1998). Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell, 95(1), 29-39. https://doi.org/10.1016/S0092-8674(00)81780-8