Cellular regulation of the protein C pathway.

The protein C anticoagulant pathway regulates thrombin formation. The pathway is triggered when thrombin binds to the endothelial cell proteoglycan, thrombomodulin. Unlike thrombin, this complex is a potent activator of the protein C zymogen, but it cannot clot blood. Activated protein C binds to protein S on cell surfaces where it proteolytically inactivates coagulation factors Va and VIIIa. Activated protein C also binds to a newly identified endothelial protein C receptor. Congenital deficiencies in this pathway are associated with thrombotic disease, and inflammation can cause acquired deficiencies. Activated protein C appears to inhibit inflammation. Thus, this pathway modulates both coagulation and inflammation.