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.1998 Nov 13;282(5392):1318-21.
doi: 10.1126/science.282.5392.1318.

Regulation of cell death protease caspase-9 by phosphorylation

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Regulation of cell death protease caspase-9 by phosphorylation

M H Cardone et al. Science..

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.

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  • Science. 2000 Feb 25;287(5457):1363

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