Role of the protein kinase C lambda/iota isoform in nuclear factor-kappaB activation by interleukin-1beta or tumor necrosis factor-alpha: cell type specificities.

It has previously been reported that distinct signaling pathways can lead to nuclear factor (NF)-kappaB activation following stimulation of different cell types with inflammatory cytokines. As the role of atypical protein kinase C (PKC) isoforms in NF-kappaB activation remains a matter of controversy, we investigated whether this role might be cell type-dependent. Immunoblots detected atypical PKC expression in all the analyzed cell lines. The PKC inhibitor calphostin C inhibited NF-kappaB activation by tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta in Jurkat or NIH3T3 cells but not in MCF7 A/Z cells. Cell transfections with a PKC lambda/iota dominant negative mutant abolished TNF-alpha-induced NF-kappaB-dependent transcription in NIH3T3 and Jurkat cells but not in MCF7 A/Z cells. Similarly, the same mutant blocked NF-kappaB-dependent transactivation after IL-1beta stimulation of NIH3T3 cells, but was ineffective after IL-1beta treatment of MCF7 A/Z cells. In MCF7 A/Z cells, however, the PKC lambda/iota dominant negative mutant could abolish transactivation of an AP-1-dependent reporter plasmid after stimulation with TNF-alpha but not with IL-1beta. These data thus confirm that transduction pathways for NF-kappaB activation after cell stimulation with TNF-alpha or IL-1beta are cell-type specific and that atypical PKC isoforms participate in this pathway in NIH3T3 and Jurkat cells.