Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60

Journal Article · Sat Mar 01 00:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.5.1334· OSTI ID:5550045

Kraft, A S; Smith, J B; Berkow, R L

Phorbol esters bind to and activate a calcium phospholipid-dependent protein kinase (C kinase). Some researchers believe that activation of C kinase is necessary for the induction of phorbol ester biologic effects. The authors' research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60. Bryostatin activates partially purified C kinase from HL-60 cells in vitro, and when applied to HL-60 cells in vivo, it decreases measurable cytoplasmic C kinase activity. Unlike the phorbol esters, bryostatin is unable to induce a macrophage-like differentiation of HL-60 cells; however, bryostatin, in a dose-dependent fashion, blocks phorbol ester-induced differentiation of HL-60 cells and, if applied within 48 hr of phorbol esters, halts further differentiation. These results suggest that activation of the C kinase by some agents is not sufficient for induction of HL-60 cell differentiation and imply that some of the biologic effects of phorbol esters may occur through a more complex mechanism than previously thought.

• Research Organization: Univ. of Alabama, Birmingham
• OSTI ID: 5550045
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 83:5
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
LACTONES
BIOLOGICAL EFFECTS
PHORBOL ESTERS
TUMOR CELLS
CELL DIFFERENTIATION
ATP
ENZYME INDUCTION
LEUKEMIA
MOLECULAR STRUCTURE
PHOSPHORUS 32
PHOSPHOTRANSFERASES
RECEPTORS
TRITIUM COMPOUNDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARCINOGENS
DAYS LIVING RADIOISOTOPES
DISEASES
ENZYMES
ESTERS
GENE REGULATION
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MEMBRANE PROTEINS
NEOPLASMS
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
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