Bryostatin induces changes in protein kinase C location and activity without altering c-myc gene expression in human promyelocytic leukemia cells (HL-60)

Andrew Kraft, V. V. Baker, W. S. May

Research output: Contribution to journalArticle

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Abstract

When human promyelocytic leukemia cells (HL-60) are induced by phorbol esters to differentiate to macrophages, the process is accompanied by immediate activation of protein kinase C (PK-C) in the cytoplasm and later changes in DNA and RNA synthesis. Although these events are temporarily related, it remains unclear how activation of this protein kinase leads to changes in nuclear transcription. In this study, we find that bryostatin, a macrocyclic lactone which does not induce differentiation of HL-60 cells but activates PK-C, mimics the effects of phorbol esters on protein phosphorylation and PK-C location. Treatment of HL-60 cells with bryostatin stimulates phosphorylation of the surface transferrin receptor and in the cytoplasm of five proteins having the molecular weights of 17-43 kDa over the same time course as that stimulated by phorbol esters. Similarly, prolonged treatment with bryostatin, like that with phorbol esters, causes the loss of all cellular PK-C activity. Unlike the phosphorylation studies, bryostatin treatment, over a 1-100 nM concentration range and for varying lengths of time, did not affect HL-60 c-myc RNA levels, while phorbol ester treatment rapidly decreased c-myc RNA levels. These data suggest that neither the activation of PK-C and the phosphorylation of specific substrates nor the loss of total cellular PK-C activity from HL-60 cells is sufficient to induce marked decreases in c-myc levels and differentiation of HL-60 cells.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalOncogene
Volume1
Issue number2
StatePublished - 1987
Externally publishedYes

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Bryostatins
myc Genes
HL-60 Cells
Protein Kinase C
Phorbol Esters
Leukemia
Gene Expression
Phosphorylation
RNA
Cytoplasm
Transferrin Receptors
Lactones
Protein Kinases
Proteins
Molecular Weight
Macrophages
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Bryostatin induces changes in protein kinase C location and activity without altering c-myc gene expression in human promyelocytic leukemia cells (HL-60). / Kraft, Andrew; Baker, V. V.; May, W. S.

In: Oncogene, Vol. 1, No. 2, 1987, p. 111-118.

Research output: Contribution to journalArticle

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