The Endothelial Cell Protein C Receptor

The Protein C Pathway before EPCR The protein C anticoagulant pathway is recognized as a major control mechanism of blood coagulation [reviewed in]. Defects in protein C, protein S and thrombomodulin have all been implicated as predisposing factors for the development of venous thrombosis (2-5) and, under some circumstances, contributing to arterial thrombosis (6-8). The pathway is initiated when thrombin binds to thrombomodulin (TM), an integral membrane receptor found primarily on endothelium, but also on a variety of other cells including monocytes. The thrombin-TM complex activates protein C rapidly and can also activate a procarboxypeptidase B, often referred to as TAFI, thrombin activatable fibrinolysis inhibitor. Once activated protein C (APC) is generated, it binds to protein S and can then inactivate either factor Va or factor VIIIa on the surface of negatively charged phospholipids or on the membranes of activated cells. The thrombin-TM complex is inhibited by either antithrombin or protein C inhibitor. The estimated half life of the complex at plasma levels of these inhibitors is only a few seconds. Since EPCR is among the newest proteins in the coagulation/anticoagulation area to be identified, I have included references to abstracts in this review that are yet to be published in full.