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.
Laboratory of Medical Chemistry/Medical Oncology, University of Liège, Belgium.
G
G
Bonizzi
J
J
Piette
S
S
Schoonbroodt
M P
MP
Merville
V
V
Bours
D016475:3T3 Cells; D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000097782:NF-kappaB-Inducing Kinase; D000099293:Protein Kinase C-lambda
D007375:Interleukin-1; D007527:Isoenzymes; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; D000099293:Protein Kinase C-lambda