Bryostatins activate protein kinase C in intact human platelets

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

Title: Bryostatins activate protein kinase C in intact human platelets

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Abstract

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 mimicmore »« less

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

Publication Date:: Thu May 01 00:00:00 EDT 1986

Research Org.:: Univ. of Alabama, Birmingham

OSTI Identifier:: 5090294

Report Number(s):: CONF-8606151-
Journal ID: CODEN: FEPRA; TRN: 86-035163

Resource Type:: Journal Article

Journal Name:: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

Additional Journal Information:: Journal Volume: 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

Subject:: 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

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                    Smith, J B, Tallant, E A, Pettit, G R, and Wallace, R W. Bryostatins activate protein kinase C in intact human platelets.  United States: N. p., 1986. 
        Web.

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                    Smith, J B, Tallant, E A, Pettit, G R, & Wallace, R W. Bryostatins activate protein kinase C in intact human platelets.  United States.

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                    Smith, J B, Tallant, E A, Pettit, G R, and Wallace, R W. 1986.  
        "Bryostatins activate protein kinase C in intact human platelets".  United States.

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@article{osti_5090294,

  title        = {Bryostatins activate protein kinase C in intact human platelets},

  author       = {Smith, J B and Tallant, E A and Pettit, G R and Wallace, R W},

  abstractNote = {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.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/5090294},
  journal      = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number       = ,

  volume       = 45:6,

  place        = {United States},

  year         = {Thu May 01 00:00:00 EDT 1986},

  month        = {Thu May 01 00:00:00 EDT 1986}

}

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