Differential regulation of protein kinase C isozymes by bryostatin 1 and phorbol 12-myristate 13-acetate in NIH 3T3 fibroblasts

Zoltan Szallasi, Colin B. Smith, George R. Pettit, Peter M. Blumberg

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210 Scopus citations

Abstract

Bryostatin 1 and phorbol 12-myristate 13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in many systems bryostatin 1 induces only a subset of the responses to PMA and blocks those which it does not induce. We report here that in NIH 3T3 fibroblasts PMA showed similar potencies for translocating PKC isozymes α, δ, and ε to the Triton X-100- soluble and -insoluble fractions and for the down-regulation of the three isozymes. Bryostatin 1 was slightly more potent than PMA for translocating PKCα and was more potent than PMA for down-regulating it. Bryostatin 1 was markedly more potent than PMA for translocating PKCδ but showed a biphasic dose-response curve for down-regulating this isozyme. 1-10 nM bryostatin 1 down-regulated PKCδ to a similar extent as PMA; lower (10-100 pM) or, unexpectedly, higher (100 nM to 1 μM) doses of bryostatin 1 caused either no or reduced down-regulation. Moreover, these high (100 nM to 1 μM) doses of bryostatin 1 inhibited the down-regulation of PKCδ by 1 μM PMA when coapplied. Bryostatin 1 caused translocation of PKCε with slightly higher potency than PKCδ, but there was no protection of this isozyme at any of the doses examined. Bryostatin 1 induced a long-term increase in c-Jun level. The dose-response curve for bryostatin 1 was biphasic, with maximal induction at 1-10 nM bryostatin 1, coincident with the maximal down-regulation of PKCδ. We conclude that bryostatin 1 showed substantially different regulation for PKCα, PKCδ, and PKCε, whereas PMA distinguished only weakly between these isozymes.

Original languageEnglish (US)
Pages (from-to)2118-2124
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number3
StatePublished - Jan 21 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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