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Life in the Lab

October 17, 1997

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

Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME (1997)

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

Cell 91: 231-241

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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HISTORY SHOWS AGAIN AND AGAIN HOW NATURE POINTS OUT THE FOLLY OF MEN – “GODZILLA,” BLUE OYSTER CULT

Sandeep Robert Datta, MD, Ph.D Department of Neurobiology Harvard Medical School