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

Biochem Pharmacol. 1999 Mar 15;57(6):713-20. doi: 10.1016/s0006-2952(98)00353-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Enzyme Activation
  • Humans
  • Interleukin-1 / pharmacology*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / biosynthesis
  • Isoenzymes / physiology*
  • Mice
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / biosynthesis
  • Protein Kinase C / physiology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Interleukin-1
  • Isoenzymes
  • Tumor Necrosis Factor-alpha
  • Protein Serine-Threonine Kinases
  • Protein Kinase C
  • protein kinase C lambda
  • NF-kappa B kinase