The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. |
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Authors: | D J Stearns-Kurosawa S Kurosawa J S Mollica G L Ferrell C T Esmon |
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Affiliation: | Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, USA. |
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Abstract: | 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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