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

SR Datta, H Dudek, X Tao, S Masters, H Fu, Y Gotoh… - Cell, 1997 - cell.com
SR Datta, H Dudek, X Tao, S Masters, H Fu, Y Gotoh, ME Greenberg
Cell, 1997cell.com
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 …
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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