Effects of resveratrol on the autophosphorylation of phorbol ester- responsive protein kinases: Inhibition of protein kinase D but not protein kinase C isozyme autophosphorylation

  • Stewart J
  • Christman K
  • O’Brian C
  • 1

    Readers

    Mendeley users who have this article in their library.
  • 52

    Citations

    Citations of this article.

Abstract

The natural product resveratrol is a potent antagonist of phorbol ester- mediated tumor promotion and in vitro cellular responses to phorbol-ester tumor promoters, but it is only weakly inhibitory against the phosphorylation of conventional exogenous substrates by phorbol ester-responsive protein kinase C (PKC) isozymes. In this report, we compare the effects of resveratrol against the autophosphorylation reactions of PKC isozymes versus the novel phorbol ester-responsive kinase, protein kinase D (PKD). We found that resveratrol inhibits PKD autophosphorylation in a concentration- dependent manner, but has only negligible effects against the autophosphorylation reactions of representative members of each PKC isozyme subfamily (cPKC-α, -β1, and -γ, nPKC-δ and -ε, and aPKC-ζ). Resveratrol was comparably effective against PKD autophosphorylation (IC50= 52 μM) and PKD phosphorylation of the exogenous substrate syntide-2 (IC50= 36 μM). The inhibitory potency of resveratrol against PKD is in line with the potency of resveratrol observed in cellular systems and with its potency against other purified enzymes and binding proteins that are implicated in the cancer chemopreventive activity of the polyphenol. Thus, PKD inhibition may contribute to the cancer chemopreventive action of resveratrol. © 2000 Elsevier Science Inc.

Author-supplied keywords

  • Cancer chemoprevention
  • Phorbol ester
  • Protein kinase C
  • Protein kinase D
  • Resveratrol
  • Tumor promotion

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Jubilee R. Stewart

  • Karen L. Christman

  • Catherine A. O’Brian

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free