Evidence for the in vitro and in vivo interaction of Ras with protein kinase C zeta.

TitleEvidence for the in vitro and in vivo interaction of Ras with protein kinase C zeta.
Publication TypeJournal Article
Year of Publication1994
AuthorsDiaz-Meco MT, Lozano J, Municio MM, Berra E, Frutos S, Sanz L, Moscat J
JournalJ Biol Chem
Date Published1994 Dec 16
KeywordsBase Sequence, Cell Division, DNA Primers, Enzyme Activation, Guanine Nucleotides, In Vitro Techniques, Molecular Sequence Data, Platelet-Derived Growth Factor, Protein Binding, Protein Kinase C, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, Proto-Oncogene Proteins p21(ras), Recombinant Fusion Proteins, Signal Transduction

The zeta isoform of protein kinase C (zeta PKC) has been shown to be involved in the maturation of Xenopus oocytes and mitogenic signaling in fibroblasts. zeta PKC also regulates the important transcription factor nuclear factor kappa B, most probably by phosphorylation of the inhibitory molecule I kappa B. The mechanisms that control zeta PKC activity are still poorly characterized. This kinase is not activated by diacylglycerol but is potently stimulated in vitro by the products of phosphatidylinositol 3-kinase (PI 3-kinase), which suggests that zeta PKC is at least one of the critical targets of PI 3-kinase-triggered signals, and strengthens its role in cell proliferation. PI 3-kinase has been shown, like Raf, to be a direct effector of Ras. zeta PKC is a required step for Ras mitogenic signaling. Therefore, it is possible that zeta PKC directly interacts with Ras during mitogenic activation. We demonstrate here that Ras interacts in vitro with the regulatory domain of zeta PKC as well as that the association of zeta PKC with Ras in vivo is triggered by platelet-derived growth factor. It is also shown here that the expression of a dominant negative mutant of Ras (Asn-17) severely impairs the activation of zeta PKC in mouse fibroblasts.

Alternate JournalJ Biol Chem
PubMed ID7989344
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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