Abstract
Caspases are intracellular proteases that function as initiators and effectors of apoptosis. The kinase Akt and p21-Ras, an Akt activator, induced phosphorylation of pro-caspase-9 (pro-Casp9) in cells. Cytochrome c-induced proteolytic processing of pro-Casp9 was defective in cytosolic extracts from cells expressing either active Ras or Akt. Akt phosphorylated recombinant Casp9 in vitro on serine-196 and inhibited its protease activity. Mutant pro-Casp9(Ser196Ala) was resistant to Akt-mediated phosphorylation and inhibition in vitro and in cells, resulting in Akt-resistant induction of apoptosis. Thus, caspases can be directly regulated by protein phosphorylation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis*
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Caspase 9
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Caspase Inhibitors
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Caspases / metabolism*
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Cell Line
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Cytochrome c Group / pharmacology
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Enzyme Precursors / metabolism
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Humans
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Mass Spectrometry
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Mutation
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Peptide Fragments / metabolism
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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 p21(ras) / metabolism
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Recombinant Fusion Proteins / metabolism
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Transfection
Substances
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Caspase Inhibitors
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Cytochrome c Group
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Enzyme Precursors
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Peptide Fragments
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Phosphoserine
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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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CASP9 protein, human
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Caspase 9
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Caspases
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)