Protein kinase C zeta associates with death inducing signaling complex and regulates Fas ligand-induced apoptosis.

Previous studies have shown that Protein kinase C (PKC) stimulation may interfere with Fas signaling pathway and Fas ligand (FasL)-induced apoptosis. In this study, we investigated in Jurkat cells, a FasL-sensitive human T-cell model, whether PKC(zeta) targets apical events of Fas signaling. We describe for the first time that in Jurkat cells, both PKC(zeta) and Prostate apoptosis response-4 (Par-4), one of the major endogenous PKC(zeta) regulators, are components of the death inducing signaling complex (DISC). Using PKC(zeta) overexpressing cells or si-RNA depletion, we demonstrate that PKC(zeta) interferes neither with Fas expression nor Fas clustering in raft microdomains, but negatively regulates FasL-induced apoptosis by interfering with DISC formation and subsequent caspase-8 processing.