Role of the protein kinase C λ/ι isoform in nuclear factor-κB activation by interleukin-1β or tumor necrosis factor-α: cell type specificities

It has previously been reported that distinct signaling pathways can lead to nuclear factor (NF)-κB activation following stimulation of different cell types with inflammatory cytokines. As the role of atypical protein kinase C (PKC) isoforms in NF-κB 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-κB activation by tumor necrosis factor (TNF)-α or interleukin (IL)-1β in Jurkat or NIH3T3 cells but not in MCF7 A/Z cells. Cell transfections with a PKC λ/ι dominant negative mutant abolished TNF-α-induced NF-κB-dependent transcription in NIH3T3 and Jurkat cells but not in MCF7 A/Z cells. Similarly, the same mutant blocked NF-κB-dependent transactivation after IL-1β stimulation of NIH3T3 cells, but was ineffective after IL-1β treatment of MCF7 A/Z cells. In MCF7 A/Z cells, however, the PKC λ/ι dominant negative mutant could abolish transactivation of an AP-1-dependent reporter plasmid after stimulation with TNF-α but not with IL-1β. These data thus confirm that transduction pathways for NF-κB activation after cell stimulation with TNF-α or IL-1β are cell-type specific and that atypical PKC isoforms participate in this pathway in NIH3T3 and Jurkat cells. Copyright (C) 1999 Elsevier Science Inc.