Mimicry of bryostatin 1 induced phosphorylation patterns in HL-60 cells by high phorbol ester concentrations

B. S. Warren, Y. Kamano, George Pettit, P. M. Blumberg

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21 Citations (Scopus)

Abstract

The bryostatins are a group of macrocyclic lactones isolated from the marine bryozoan Bugula neritina. Bryostatin 1, like the phorbol esters, activates protein kinase C; however, it partially inhibits the phorbol ester induced differentiation of the human promyelocytic leukemic cell line HL-60. We compared the phosphorylation response in HL-60 cells treated with phorbol 12,13-dibutyrate or bryostatin 1. Bryostatin 1 enhanced the phosphorylation of the same proteins as did typical concentrations (10-8-10-9 M) of phorbol 12,13-dibutyrate. In addition, bryostatin 1 caused the appearance of 2 phosphorylated protein spots with molecular weights of 70,000 and pIs of 6.3-6.4. These latter phosphorylations were evident after a 30-min exposure to bryostatin 1 at 6 nM. Phorbol 12,13-dibutyrate concentrations of at least 600 nM, approximately 100-fold that necessary to induce differentiation, also induced the appearance of these phosphoprotein spots. The M(r) 70,000 phosphoproteins were located in the ionic detergent-soluble cellular fraction which would contain the cytoskeletal proteins. Their phosphorylation was almost totally on serine residues. We speculate that phorbol esters at very high concentrations may more closely resemble bryostatin 1.

Original languageEnglish (US)
Pages (from-to)5984-5988
Number of pages5
JournalCancer Research
Volume48
Issue number21
StatePublished - 1988

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HL-60 Cells
Phorbol Esters
Phosphorylation
Phorbol 12,13-Dibutyrate
Phosphoproteins
Bryostatins
Cytoskeletal Proteins
Lactones
Detergents
Serine
Protein Kinase C
bryostatin 1
Proteins
Molecular Weight
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Mimicry of bryostatin 1 induced phosphorylation patterns in HL-60 cells by high phorbol ester concentrations. / Warren, B. S.; Kamano, Y.; Pettit, George; Blumberg, P. M.

In: Cancer Research, Vol. 48, No. 21, 1988, p. 5984-5988.

Research output: Contribution to journalArticle

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