Abstract
BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway.
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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Androstadienes / pharmacology
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Animals
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Apoptosis
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Carrier Proteins / metabolism*
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Cell Line
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Chromones / pharmacology
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Humans
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Interleukin-3 / pharmacology*
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Mice
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Phosphoserine / metabolism
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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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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Recombinant Proteins / metabolism
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Signal Transduction
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Wortmannin
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bcl-Associated Death Protein
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bcl-X Protein
Substances
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Androstadienes
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BAD protein, human
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BCL2L1 protein, human
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Bad protein, mouse
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Bcl2l1 protein, mouse
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Carrier Proteins
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Chromones
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Enzyme Inhibitors
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Interleukin-3
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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bcl-Associated Death Protein
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bcl-X Protein
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Phosphoserine
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Wortmannin