Akt phosphorylation of BAD couples survival signals to the cell- intrinsic death machinery

Abstract

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its down-stream 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.