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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells / physiology
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Amino Acid Sequence
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Animals
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Carrier Proteins / metabolism*
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Cell Death / drug effects
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Cell Death / physiology
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Cell Survival / physiology
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Insulin-Like Growth Factor I / pharmacology
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Neurons / cytology*
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Neurons / enzymology*
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Serine / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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bcl-Associated Death Protein
Substances
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Bad protein, mouse
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Carrier Proteins
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Proto-Oncogene Proteins
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bcl-Associated Death Protein
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Serine
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Insulin-Like Growth Factor I
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt