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, 91 (2), 231-41

Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery

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Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery

S R Datta et al. Cell.

Abstract

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

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