A dominant negative protein kinase C zeta subspecies blocks NF-kappa B activation.

TitleA dominant negative protein kinase C zeta subspecies blocks NF-kappa B activation.
Publication TypeJournal Article
Year of Publication1993
AuthorsDiaz-Meco MT, Berra E, Municio MM, Sanz L, Lozano J, Dominguez I, Diaz-Golpe V, de Lera MTLain, Alcamí J, Payá CV, Arenzana-Seisedos F, Virelizier JL, Moscat J
JournalMol Cell Biol
Date Published1993 Aug
Keywords3T3 Cells, Animals, Base Sequence, Cell Compartmentation, Cloning, Molecular, Enhancer Elements, Genetic, Gene Expression Regulation, Genes, Dominant, In Vitro Techniques, Mice, Molecular Sequence Data, Mutation, NF-kappa B, Oligodeoxyribonucleotides, Protein Kinase C, Transcriptional Activation, Transfection

Nuclear factor kappa B (NF-kappa B) plays a critical role in the regulation of a number of genes. NF-kappa B is a heterodimer of 50- and 65-kDa subunits sequestered in the cytoplasm complexed to inhibitory protein I kappa B. Following stimulation of cells, I kappa B dissociates from NF-kappa B, allowing its translocation to the nucleus, where it carries out the transactivation function. The precise mechanism controlling NF-kappa B activation and the involvement of members of the protein kinase C (PKC) family of isotypes have previously been investigated. It was found that phorbol myristate acetate, (PMA) which is a potent stimulant of phorbol ester-sensitive PKC isotypes, activates NF-kappa B. However, the role of PMA-sensitive PKCs in vivo is not as apparent. It has recently been demonstrated in the model system of Xenopus laevis oocytes that the PMA-insensitive PKC isotype, zeta PKC, is a required step in the activation of NF-kappa B in response to ras p21. We demonstrate here that overexpression of zeta PKC is by itself sufficient to stimulate a permanent translocation of functionally active NF-kappa B into the nucleus of NIH 3T3 fibroblasts and that transfection of a kinase-defective dominant negative mutant of zeta PKC dramatically inhibits the kappa B-dependent transactivation of a chloramphenicol acetyltransferase reporter plasmid in NIH 3T3 fibroblasts. All these results support the notion that zeta PKC plays a decisive role in NF-kappa B regulation in mammalian cells.

Alternate JournalMol Cell Biol
PubMed ID8336714
PubMed Central IDPMC360103
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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