Role of protein kinase C in arginine vasopressin-stimulated ERK and p70S6 kinase phosphorylation

Paramita M Ghosh, Roble Bedolla, Charles A. Thomas, Jeffrey I. Kreisberg

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

We previously showed in rat renal glomerular mesangial cells, that arginine vasopressin (AVP)-stimulated cell proliferation was mediated by epidermal growth factor receptor (EGF-R) transactivation, and activation (phosphorylation) of ERK1/2 and p70S6 kinase (Ghosh et al. [2001]: Am J Physiol Renal Physiol 280:F972-F979]. In this paper, we extend these observations and show that different protein kinase C (PKC) isoforms play different roles in mediating AVP-stimulated ERK1/2 and p70S6 kinase phosphorylation and cell proliferation. AVP treatment for 0-60 min stimulated the serine/threonine phosphorylation of PKC isoforms α, δ, ε, and ζ. The activation of PKC was dependent on EGF-R and phosphatidylinositol 3-kinase (PI3K) activation. In addition, inhibition of conventional and novel PKC isoforms by chronic (24 h) exposure to phorbol 12-myristate 13-acetate (PMA) inhibited AVP-induced activation of ERK and p70S6 kinase as well as EGF-R phosphorylation. Rottlerin, a specific inhibitor of PKCδ, inhibited both ERK and p70S6 kinase phosphorylation and cell proliferation. In contrast, a PKCε translocation inhibitor decreased ERK1/2 activation without affecting p70S6 kinase or cell proliferation, while a dominant negative PKCζ (K281W) cDNA delayed p70S6 kinase activation without affecting ERK1/2. On the other hand, Gö6976, an inhibitor of conventional PKC isoforms, did not affect p70S6 kinase, but stimulated ERK1/2 phosphorylation without affecting cell proliferation. Our results indicate that PKCδ plays an important role in AVP-stimulated ERK and p70S6 kinase activation and cell proliferation.

Original languageEnglish (US)
Pages (from-to)1109-1129
Number of pages21
JournalJournal of Cellular Biochemistry
Volume91
Issue number6
DOIs
StatePublished - 2004
Externally publishedYes

Keywords

  • EGF-R
  • PI3K
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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