Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.
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.
del Peso
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Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
González-García
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M
Page
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C
Herrera
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R
Nuñez
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G
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D000077191:Wortmannin; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
D000730:Androstadienes; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D007377:Interleukin-3; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D000077191:Wortmannin; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; C494819:BAD protein, human; C494811:BCL2L1 protein, human; C494820:Bad protein, mouse; C494812:Bcl2l1 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human