CASPASE-3-MEDIATED CLEAVAGE OF PROTEIN-KINASE-C-THETA IN INDUCTION OFAPOPTOSIS

Protein kinase C theta (PKC theta) is a member of the novel or nPKC fa mily. 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 blocke d in cells that overexpress the anti-apoptotic Bcl-x(L) or the baculov irus p35 protein. PKC theta is cleaved by Caspase-3 and by apoptotic c ell lysates at a DEVD354/K site. We also show that overexpression of t he cleaved kinase-active PKC theta fragment, but not full-length PKC t heta or a kinase-inactive fragment, results in induction of sub-G(1) p hase DNA, nuclear fragmentation, and lethality. These findings indicat e that proteolytic cleavage of PKC theta by Caspase-3 induces events c haracteristic of apoptosis.