TY - JOUR
T1 - Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
AU - Stambolic, Vuk
AU - Suzuki, Akira
AU - De la Pompa, José Lois
AU - Brothers, Greg M.
AU - Mirtsos, Christine
AU - Sasaki, Takehiko
AU - Ruland, Jurgen
AU - Penninger, Josef M.
AU - Siderovski, David P.
AU - Mak, Tak W.
N1 - Funding Information:
We would like to thank Bryan Snow, Stephen Chung, Andrew Elia, Denis Bouchard, Joan Mangion, and Shayna Delovitch for technical assistance; Jing Jin and James R. Woodgett for providing reagents and data prior to publication; Shoukat Dedhar for providing data prior to publication; Garry Nolan for providing retroviral vectors and φNX cells; Alex Grossman, Lea Harrington, and Christian Sirard for critical reading of the manuscript; and Miki Sato for her support. J. R. is supported by a fellowship from the Deutsche Forschungsgemeinschaft.
PY - 1998/10/2
Y1 - 1998/10/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032475861&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81780-8
DO - 10.1016/S0092-8674(00)81780-8
M3 - Article
C2 - 9778245
AN - SCOPUS:0032475861
SN - 0092-8674
VL - 95
SP - 29
EP - 39
JO - Cell
JF - Cell
IS - 1
ER -