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Science. 1998 Nov 13;282(5392):1318-21.

Regulation of cell death protease caspase-9 by phosphorylation.

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  • 1Program on Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, CA 92037, USA.

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.

Comment in

  • Science. 2000 Feb 25;287(5457):1363.
PMID:
9812896
[PubMed - indexed for MEDLINE]
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