Bryostatins activate protein kinase C in intact human platelets

Journal Article · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5090294

Smith, J B; Tallant, E A; Pettit, G R; Wallace, R W

Bryostatins, macrocyclic lactones isolated from a marine bryozoan, have antineoplastic activity in the P388 lymphocytic leukemia system. These compounds also stimulate growth in Swiss 3T3 cells, induce secretion in leukocytes, inhibit phorbol dibutyrate binding to a high affinity receptor, and activate the C-kinase in vitro. In human platelets, phorbol esters induce aggregation and activate protein kinase C, resulting in phosphorylation of a 47K protein and the 20K myosin light chain. The authors now show that bryostatin 7 (B-7) triggers platelet aggregation to the same rate and extent as phorbol 12-myristate 13-acetate (PMA). B-7 also causes the in vivo activation of the C-kinase, resulting in phosphorylation of both the 47K and the 20K proteins; the time courses and dose-responses of these B-7-induced phosphorylations were similar to those found with PMA. In addition, B-7 increases the level of /sup 32/P-incorporation into the platelet polyphosphoinositides, which also occurs in response to PMA. Bryostatin 3 (B-3), which has been shown to be much less potent than B-7 in mimicking other PMA effects, was much less effective than PMA or B-7 in inducing platelet aggregation and in stimulating /sup 32/P-incorporation into both proteins and the phosphoinositides. These results demonstrate that, intact human platelets, bryostatins mimic the phorbol esters tumor promoters and directly activate protein kinase C.

• Research Organization: Univ. of Alabama, Birmingham
• OSTI ID: 5090294
• Report Number(s): CONF-8606151-; TRN: 86-035163
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
• 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
BLOOD PLATELETS
BLOOD COAGULATION
LACTONES
BIOCHEMICAL REACTION KINETICS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOTRANSFERASES
ENZYME ACTIVITY
LYMPHOCYTES
MAN
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORYLATION
PROTEINS
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ENZYMES
ESTERS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEUKOCYTES
LIGHT NUCLEI
LIPIDS
MAMMALS
MATERIALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PRIMATES
RADIOISOTOPES
REACTION KINETICS
SOMATIC CELLS
TRANSFERASES
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques