Role of the protein kinase C lambda/iota isoform in nuclear factor-kappa Bactivation by interleukin-1 beta or tumor necrosis factor-alpha: Cell typespecificities

It has previously been reported that distinct signaling pathways can lead t o nuclear factor (NF)-kappa B activation following stimulation of different cell types with inflammatory cytokines. As the role of atypical protein ki nase C (PKC) isoforms in NF-kappa B activation remains a matter of controve rsy, we investigated whether this role might be cell type-dependent. Immuno blots detected atypical PKC expression in all the analyzed cell lines. The PKC inhibitor calphostin C inhibited NF-kappa B activation by tumor necrosi s factor (TNF)-alpha or interleukin (IL)-1 beta in Jurkat or NIH3T3 cells b ut not in MCF7 A/Z cells. Cell transfections with a PKC lambda/iota dominan t negative mutant abolished TNF-alpha-induced NF-kappa B-dependent transcri ption in NIH3T3 and Jurkat cells but not in MCF7 A/Z cells. Similarly, the same mutant blocked NF-kappa B-dependent transactivation after IL-1 beta st imulation of NIH3T3 cells, but was ineffective after IL-1 beta treatment of MCF7 A/Z cells. In MCF7 A/Z cells, however, the PKC lambda/iota dominant n egative mutant could abolish transactivation of an AP-l-dependent reporter plasmid after stimulation with TNF-alpha but not with IL-1 beta. These data thus confirm that transduction pathways for NF-kappa B activation after ce ll stimulation with TNF-alpha or IL-1 beta are cell-type specific and that atypical PKC isoforms participate in this pathway in NIH3T3 and Jurkat cell s. (C) 1999 Elsevier Science Inc.