title: 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 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.
authors.affiliation: Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Datta
authors.forename: H
authors.initials: H
authors.lastname: Dudek
authors.forename: X
authors.initials: X
authors.lastname: Tao
authors.forename: S
authors.initials: S
authors.lastname: Masters
authors.forename: H
authors.initials: H
authors.lastname: Fu
authors.forename: Y
authors.initials: Y
authors.lastname: Gotoh
authors.forename: M E
authors.initials: ME
authors.lastname: Greenberg
mesh_terms: D016475:3T3 Cells / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051025:bcl-Associated Death Protein
chemical_list: C494820:Bad protein, mouse; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D051025:bcl-Associated Death Protein; D012694:Serine; D007334:Insulin-Like Growth Factor I; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt