Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis

Protein kinase C theta (PKC theta) is a member of the novel or nPKC family. A functional role for PKC theta is unknown. The present studies demonstrate that PKC theta is cleaved in the third variable region (V3) in apoptosis induced by diverse agents. PKC theta cleavage is blocked in cells that overexpress the anti-apoptotic Bcl-x(L) or the baculovirus p35 protein. PKC theta is cleaved by Caspase-3 and by apoptotic cell lysates at a DEVD354/K site. We also show that overexpression of the cleaved kinase-active PKC theta fragment, but not full-length PKC theta or a kinase-inactive fragment, results in induction of sub-G(1) phase DNA, nuclear fragmentation, and lethality. These findings indicate that proteolytic cleavage of PKC theta by Caspase-3 induces events characteristic of apoptosis.