Caspase-3-mediated Cleavage of Protein Kinase C θ in Induction of Apoptosis*

Protein kinase C θ (PKCθ) is a member of the novel or nPKC family. A functional role for PKCθ is unknown. The present studies demonstrate that PKCθ is cleaved in the third variable region (V3) in apoptosis induced by diverse agents. PKCθ cleavage is blocked in cells that overexpress the anti-apoptotic Bcl-xL or the baculovirus p35 protein. PKCθ 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 PKCθ fragment, but not full-length PKCθ or a kinase-inactive fragment, results in induction of sub-G1phase DNA, nuclear fragmentation, and lethality. These findings indicate that proteolytic cleavage of PKCθ by Caspase-3 induces events characteristic of apoptosis.

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