Proteolytic activation of PKN by caspase-3 or related protease during apoptosis.
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Takahashi M, Mukai H, Toshimori M, Miyamoto M, Ono Y
Proteolytic activation of PKN by caspase-3 or related protease during apoptosis.
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11566-71.
- PubMed ID
- 9751706 [ View in PubMed]
- Abstract
PKN, a fatty acid- and Rho-activated serine/threonine kinase having a catalytic domain highly homologous to protein kinase C (PKC), was cleaved at specific sites in apoptotic Jurkat and U937 cells on Fas ligation and treatment with staurosporin or etoposide, respectively. The cleavage of PKN occurred with a time course similar to that of PKCdelta, a known caspase substrate. This proteolysis was inhibited by a caspase inhibitor, acetyl-Asp-Glu-Val-Asp-aldehyde. The cleavage fragments were generated in vitro from PKN by treatment with recombinant caspase-3. Site-directed mutagenesis of specific aspartate residues prevented the appearance of these fragments. These results indicate that PKN is cleaved by caspase-3 or related protease during apoptosis. The major proteolysis took place between the amino-terminal regulatory domain and the carboxyl-terminal catalytic domain, and it generated a constitutively active kinase fragment. The cleavage of PKN may contribute to signal transduction, eventually leading to apoptosis.