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.
INSERM U563/CPTP, CHU Purpan, Bât B, Dpt G. DELSOL, Equipe G. LAURENT, CHU Purpan, BP 3028, 31024 Toulouse Cedex 3, France.
Ingrid
I
Leroy
Aurélie
A
de Thonel
Guy
G
Laurent
Anne
A
Quillet-Mary
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053222:Fas Ligand Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D000099221:Protein Kinase C zeta
D051017:Apoptosis Regulatory Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011493:Protein Kinase C; D018124:Receptors, Tumor Necrosis Factor; D000099221:Protein Kinase C zeta; C505661:FASLG protein, human; C101296:prostate apoptosis response-4 protein