Cleavage of zeta PKC but not lambda/iota PKC by caspase-3 during UV-induced apoptosis

The stimulation of caspases is a critical event in apoptotic cell death. Se veral kinases critically involved in cell proliferation pathways have been shown to be cleaved by caspase-mediated mechanisms, Thus, the degradation o f delta protein kinase C (PKC) and MEKK-1 by caspase-3 generates activated fragments corresponding to their catalytic domains, consistent with the obs ervations that both enzymes are important for apoptosis. In contrast, other kinases reported to have anti-apoptotic properties, such as Raf-1 and Akt, are inactivated by proteolytic degradation by the caspase system. Since th e atypical PKCs have been shown to play critical roles in cell survival, in the study reported here we have addressed the potential degradation of the se PKCs by the caspase system in UV-irradiated HeLa cells. Herein we show t hat although zeta PKC and lambda/iota PKC are both inhibited in UV-treated cells, only zeta PKC but not lambda/iota PKC is cleaved by a caspase-mediat ed process. This cleavage generates a fragment that corresponds to its cata lytic domain that is enzymatically inactive, The sequence where caspase-3 c leaves zeta PKC was mapped, and a mutant resistant to degradation was shown to protect cells from apoptosis more efficiently than the wild-type enzyme .