title: A dominant negative protein kinase C zeta subspecies blocks NF-kappa B activation.
abstract: 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.
authors.affiliation: Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Spain.
authors.forename: M T
authors.initials: MT
authors.lastname: Diaz-Meco
authors.forename: E
authors.initials: E
authors.lastname: Berra
authors.forename: M M
authors.initials: MM
authors.lastname: Municio
authors.forename: L
authors.initials: L
authors.lastname: Sanz
authors.forename: J
authors.initials: J
authors.lastname: Lozano
authors.forename: I
authors.initials: I
authors.lastname: Dominguez
authors.forename: V
authors.initials: V
authors.lastname: Diaz-Golpe
authors.forename: M T
authors.initials: MT
authors.lastname: Lain de Lera
authors.forename: J
authors.initials: J
authors.lastname: Alcamí
authors.forename: C V
authors.initials: CV
authors.lastname: Payá
authors.forename: F
authors.initials: F
authors.lastname: Arenzana-Seisedos
authors.forename: J L
authors.initials: JL
authors.lastname: Virelizier
authors.forename: J
authors.initials: J
authors.lastname: Moscat
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D000099221:Protein Kinase C zeta
chemical_list: D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta