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The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex.
Open accessAbstract
Protein C activation on the surface of the endothelium is critical to the negative regulation of blood coagulation. We now demonstrate that monoclonal antibodies that block protein C binding to the endothelial cell protein C receptor (EPCR) reduce protein C activation rates by the thrombin-thrombomodulin complex on endothelium, but that antibodies that bind to EPCR without blocking protein C binding have no effect. The kinetic result of blocking the EPCR-protein C interaction is an increased apparent Km for the activation without altering the affinity of thrombin for thrombomodulin. Activation rates of the protein C derivative lacking the gamma-carboxyglutamic acid domain, which is required for binding to EPCR, are not altered by the anti-EPCR antibodies. These data indicate that the protein C activation complex involves protein C, thrombin, thrombomodulin, and EPCR. These observations open new questions about the control of coagulation reactions on vascular endothelium.
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Cited by
A Cell-based Model of Hemostasis
Monroe, D., & Hoffman, M. (2001) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615947 · Cited by 1,542
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Self-citation(2015) · Advances in Parasitology · doi:10.1016/bs.apar.2015.02.004 · Cited by 162
Uchiba, M., Okajima, K., Oike, Y., Ito, Y., Fukudome, K., Isobe, H., & Suda, T. (2004) · Circulation Research · doi:10.1161/01.res.0000133680.87668.fa · Cited by 162
Metadata
- Authors
- Stearns-Kurosawa, D. J., Kurosawa, S., Mollica, J. S., Ferrell, G. L., & Esmon, C. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-09-17
- Volume
- 93
- Issue
- 19
- Pages
- 10212-10216
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2073933974
- Cited by
- 528
- References
- 0
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- green
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- Stearns-Kurosawa, D. J., Kurosawa, S., Mollica, J. S., Ferrell, G. L., & Esmon, C. T. (1996). The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.19.10212
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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