Bryostatin 1 induces biphasic activation of protein kinase D in intact cells

Sharon A. Matthews, George Pettit, Enrique Rozengurt

Research output: Contribution to journalArticle

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Abstract

Bryostatin 1 and phorbol esters are both potent activators of protein kinase C (PKC), although their specific biological effects can differ in many systems. Here, we report that bryostatin 1 activates protein kinase D (PKD), a novel serine/threonine protein kinase, in intact Swiss 3T3 cells and secondary mouse embryo fibroblasts and in COS-7 cells transiently transfected with a PKD expression construct. The dose response of PKD activation induced by bryostatin 1 follows a striking biphasic pattern with maximal activation achieved at a concentration of 10 nM. Higher concentrations of bryostatin 1 (100 nM) reduced PKD activation induced by phorbol 12,13-dibutyrate to levels stimulated by bryostatin 1 alone. Bryostatin 1-induced PKD activation was markedly attenuated by treatment of cells with the PKC inhibitors bisindolylmaleimide 1 and Ro 31-8220. However, these agents did not inhibit PKD activity when added directly to in vitro kinase assays, suggesting that bryostatin 1 stimulates PKD activation through a PKC-dependent pathway in intact cells. Our results raise the possibility that activated PKD in intact cells could mediate some of the multiple biphasic biological responses induced by bryostatin 1.

Original languageEnglish (US)
Pages (from-to)20245-20250
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number32
DOIs
StatePublished - Aug 8 1997

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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