title: Protein kinase C inhibits CD95 (Fas/APO-1)-mediated apoptosis by at least two different mechanisms in Jurkat T cells.
abstract: We have recently reported that activation of protein kinase C (PKC) plays a negative role in CD95-mediated apoptosis in human T cell lines. Here we present data indicating that although the PKC-induced mitogen-activated protein kinase pathway could be partially implicated in the abrogation of CD95-mediated apoptosis by phorbol esters in Jurkat T cells, the major inhibitory effect is exerted through a PKC-dependent, mitogen-activated protein kinase-independent signaling pathway. Furthermore, we demonstrate that activation of PKC diminishes CD95 receptor aggregation elicited by agonistic CD95 Abs. On the other hand, it has been reported that UV radiation-induced apoptosis is mediated at least in part by the induction of CD95 oligomerization at the cell surface. Here we show that activation of PKC also inhibits UVB light-induced CD95 aggregation and apoptosis in Jurkat T cells. These results reveal a novel mechanism by which T cells may restrain their sensitivity to CD95-induced cell death through PKC-mediated regulation of CD95 receptor oligomerization at the cell membrane.
authors.affiliation: Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Cientificas, Granada, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ruiz-Ruiz
authors.forename: G
authors.initials: G
authors.lastname: Robledo
authors.forename: J
authors.initials: J
authors.lastname: Font
authors.forename: M
authors.initials: M
authors.lastname: Izquierdo
authors.forename: A
authors.initials: A
authors.lastname: López-Rivas
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D048369:MAP Kinase Kinase 1; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000528:radiation effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D011940:Receptor Aggregation / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D005419:Flavonoids; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one