Proteolytic activation of protein kinase C δ and ε by caspase-3 in U937 cells during chemotherapeutic agent-induced apoptosis

Protein kinase C (PKC) family members play pivotal roles in cellular signal transduction and nPKC delta and theta are known to be subjected to restrictive proteolysis during apoptosis. Here we show that nPKC epsilon was specifically cleaved and generates 43-kDa and 36-kDa C-terminal fragments during chemotherapeutic drug-induced apoptosis. The proteolytic cleavage of nPKC delta and epsilon was completely inhibited by pretreatment with AcDFVD-cho, a specific inhibitor of caspase-3 family enzymes. Furthermore, nPKC epsilon in non-treated U937 cell lysates was cleaved by purified recombinant caspase-3 to generate the 43-kDa fragment, identical in size to the fragment observed in vivo. This cleavage was prevented by the addition of Ac-DEVD-cho. These results suggest that caspase-3 specifically cleaves nPKC epsilon. These findings suggest the possibility that nPKC subfamily members are generally involved in the execution of apoptosis but they are regulated diversely depending on the different (C) 1999 Elsevier Science Inc.