Bryostatin 1, an activator of protein kinase c, mimics as well as inhibits biological effects of the phorbol ester TPA in vivo and in vitro

M. Gschwendt, G. Fürstenberger, S. Rose-john, M. Rogers, W. Kittstein, George Pettit, C. L. Herald, F. Marks

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The macrocyclic lactone bryostatin 1 activates protein kinase C as effectively as the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Nevertheless, there are only certain TPA-effects that can be induced by bryostatin 1. These include stimulation of epidermal DNA synthesis and alkaline phosphatase activity in vivo as well as activation of the Ca2+-independent, phospholipid-requiring phosphorylation of an epidermal protein in a cell-free system. Various other TPA-effects in vivo and in vitro, which are not mimicked by bryostatin 1 can be inhibited by applying bryostatin 130 min prior to TPA. TPA-effects suppressible by bryostatin 1 include the Ca2+-dependent stimulation of arachidonic acid and prostaglandin E2 release, of ornithine decarboxylase (ODC activity and ODC-mRNA expression and of trans-glutaminase activity in keratinocytes in vivo and/or in vitro and, in addition, Epstein-Barr virus induction in Raji cells. The same is true for the conversion step (first stage of promotion) of multistage carcinogenesis. In contrast to the TPA induction of arachidonic acid and prostaglandin E2 release and of transglutaminase activity, induction by the Ca2+-ionophore and by high Ca2+-shift, respectively, are not significantly inhibited by bryostatin 1. We suggest that bryostatin 1 might inhibit a specific 'Ca2+-component' of TPA action.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalCarcinogenesis
Volume9
Issue number4
DOIs
StatePublished - Apr 1988

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Protein Kinase C
Phorbol Esters
Tetradecanoylphorbol Acetate
Protein Kinases
Esters
Ionophores
Proteins
Phosphorylation
Acids
Phospholipids
Phosphatases
Prostaglandins
Proof by induction
Viruses
DNA
Thermodynamic properties
Chemical activation
Dinoprostone
Arachidonic Acid
Carcinogenesis

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience
  • Cancer Research

Cite this

Bryostatin 1, an activator of protein kinase c, mimics as well as inhibits biological effects of the phorbol ester TPA in vivo and in vitro. / Gschwendt, M.; Fürstenberger, G.; Rose-john, S.; Rogers, M.; Kittstein, W.; Pettit, George; Herald, C. L.; Marks, F.

In: Carcinogenesis, Vol. 9, No. 4, 04.1988, p. 555-562.

Research output: Contribution to journalArticle

Gschwendt, M. ; Fürstenberger, G. ; Rose-john, S. ; Rogers, M. ; Kittstein, W. ; Pettit, George ; Herald, C. L. ; Marks, F. / Bryostatin 1, an activator of protein kinase c, mimics as well as inhibits biological effects of the phorbol ester TPA in vivo and in vitro. In: Carcinogenesis. 1988 ; Vol. 9, No. 4. pp. 555-562.
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