Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.
摘要：
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.
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关键词：
Cells, Cultured Fibroblasts Animals Mice Phosphoric Monoester Hydrolases Protein-Serine-Threonine Kinases Phosphatidylinositol Phosphates Proto-Oncogene Proteins Tumor Suppressor Proteins Cell Division
DOI：
10.1016/S0092-8674(00)81780-8
被引量：
年份：
1998
Elsevier
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Elsevier
Semantic Scholar
Semantic Scholar
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万方医学
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