AKT PHOSPHORYLATION OF BAD COUPLES SURVIVAL SIGNALS TO THE CELL-INTRINSIC DEATH MACHINERY

Growth factors can promote cell survival by activating the phosphatidy linositide-3'-OH kinase and its downstream target, the serine-threonin e 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 t he BCL-2 family member BAD, thereby suppressing apoptosis and promotin g cell survival. Akt phosphorylates BAD in vitro and in vivo, and bloc ks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly in activate a critical component of the cell-intrinsic death machinery.