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The cleaved peptide of the thrombin receptor is a strong platelet agonist

Publication ,  Journal Article
Furman, MI; Liu, L; Benoit, SE; Becker, RC; Barnard, MR; Michelson, AD
Published in: Proceedings of the National Academy of Sciences of the United States of America
1998

Thrombin cleaves its G-protein-linked seven-transmembrane domain receptor, thereby releasing a 41-aa peptide and generating a new amino terminus that acts as a tethered ligand for the receptor. Peptides corresponding to the new amino terminal end of the proteolyzed seven- transmembrane domain thrombin receptor [TR42-55, SFLLRNPNDKYEPF, also known as TRAP (thrombin receptor-activating peptide)], previously have been demonstrated to activate the receptor. In this study, we demonstrate that the 41-aa cleaved peptide, TR1-41 (MGPRRLLLVAACFSLCGPLLSARTRARRPESKATNATLDPR) is a strong platelet agonist. TR1-41 induces platelet aggregation. In whole-blood flow cytometric studies, TR1-41 was shown to be more potent than TR42-55 and almost as potent as thrombin, as determined by the degree of increase in: (i) platelet surface expression of P-selectin (reflecting α granule secretion); (ii) exposure of the fibrinogen binding site on the glycoprotein (GP) IIb-IIIa complex; and (iii) fibrinogen binding to the activated GPIIb-IIIa complex. As determined by experiments with inhibitors [prostaglandin I2, staurosporine, wortmannin, the endothelium- derived relaxing factor congener S-nitroso-N-acetylcysteine (SNAC), EDTA, EGTA, and genestein], and with Bernard-Soulier or Glanzmann's platelets, we demonstrated that TR1-41-induced platelet activation is: (i) inhibited by cyclic AMP; (ii) mediated by protein kinase C, phosphatidyl inositol-3- kinase, myosin light chain kinase, and intracellular protein tyrosine kinases; (iii) dependent on extracellular calcium; and (iv) independent of the GPIb-IX and GPIIb-IIIa complexes. TR1-41-induced platelet activation was synergistic with TR42-55. In summary, the cleaved peptide of the seven-transmembrane domain TR (TR1-41) is a strong platelet agonist.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

ISSN

0027-8424

Publication Date

1998

Volume

95

Issue

6

Start / End Page

3082 / 3087
 

Citation

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Chicago
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Furman, M. I., Liu, L., Benoit, S. E., Becker, R. C., Barnard, M. R., & Michelson, A. D. (1998). The cleaved peptide of the thrombin receptor is a strong platelet agonist. Proceedings of the National Academy of Sciences of the United States of America, 95(6), 3082–3087. https://doi.org/10.1073/pnas.95.6.3082
Furman, M. I., L. Liu, S. E. Benoit, R. C. Becker, M. R. Barnard, and A. D. Michelson. “The cleaved peptide of the thrombin receptor is a strong platelet agonist.” Proceedings of the National Academy of Sciences of the United States of America 95, no. 6 (1998): 3082–87. https://doi.org/10.1073/pnas.95.6.3082.
Furman MI, Liu L, Benoit SE, Becker RC, Barnard MR, Michelson AD. The cleaved peptide of the thrombin receptor is a strong platelet agonist. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(6):3082–7.
Furman, M. I., et al. “The cleaved peptide of the thrombin receptor is a strong platelet agonist.” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 6, 1998, pp. 3082–87. Scival, doi:10.1073/pnas.95.6.3082.
Furman MI, Liu L, Benoit SE, Becker RC, Barnard MR, Michelson AD. The cleaved peptide of the thrombin receptor is a strong platelet agonist. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(6):3082–3087.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

ISSN

0027-8424

Publication Date

1998

Volume

95

Issue

6

Start / End Page

3082 / 3087