Protein kinase C inhibits CD95 (Fas/APO-1)-mediated apoptosis by at least two different mechanisms in Jurkat T cells

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 pr esent data indicating that although the PKC-induced mitogen-activated prote in kinase pathway could be partially implicated in the abrogation of CD95-m ediated apoptosis by phorbol esters in Jurkat T cells, the major inhibitory effect is exerted:through a PKC-dependent, mitogen-activated protein kinas e-independent signaling pathway, Furthermore, we demonstrate that activatio n of PKC diminishes CD95 receptor aggregation elicited by agonistic CD95 Ab s, On the other hand, it has been reported. that UV radiation-induced apopt osis 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 resul ts reveal a novel mechanism by which T cells may restrain their sensitivity to CD95-induced cell death through PKC-mediated regulation of CD95 recepto r oligomerization at the cell membrane.