Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway.

TitleTargeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway.
Publication TypeJournal Article
Year of Publication2001
AuthorsLeitges M, Sanz L, Martin P, Duran A, Braun U, GarcĂ­a JF, Camacho F, Diaz-Meco MT, Rennert PD, Moscat J
JournalMol Cell
Date Published2001 Oct
KeywordsAcetylcysteine, Animals, Apoptosis, Cycloheximide, Cysteine Proteinase Inhibitors, DNA-Binding Proteins, Enzyme Activation, Female, Fibroblasts, Gene Targeting, Genes, Reporter, I-kappa B Kinase, I-kappa B Proteins, Interleukin-1, Lung, Lymphocyte Subsets, Male, Mice, Mice, Knockout, NF-kappa B, NF-KappaB Inhibitor alpha, Peyer's Patches, Phenotype, Phosphorylation, Protein Kinase C, Protein Synthesis Inhibitors, Protein-Serine-Threonine Kinases, Recombinant Proteins, Spleen, Transcription Factor RelA, Transcription Factors, Transcription, Genetic, Tumor Necrosis Factor-alpha

Here we have addressed the role that zetaPKC plays in NF-kappaB activation using mice in which this kinase was inactivated by homologous recombination. These mice, although grossly normal, showed phenotypic alterations in secondary lymphoid organs reminiscent of those of the TNF receptor-1 and of the lymphotoxin-beta receptor gene-deficient mice. The lack of zetaPKC in embryonic fibroblasts (EFs) severely impairs kappaB-dependent transcriptional activity as well as cytokine-induced phosphorylation of p65. Also, a cytokine-inducible interaction of zetaPKC with p65 was detected which requires the previous degradation of IkappaB. Although in zetaPKC-/- EFs this kinase is not necessary for IKK activation, in lung, which abundantly expresses zetaPKC, IKK activation is inhibited.

Alternate JournalMol Cell
PubMed ID11684013
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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