The protein C anticoagulant pathway serves as a major system for controlling thrombosis, limiting inflammatory responses, and potentially decreasing endothelial cell apoptosis in response to inflammatory cytokines and ischemia. The essential components of the pathway involve thrombin, thrombomodulin, the endothelial cell protein C receptor (EPCR), protein C and protein S. The pathway is initiated when thrombin binds to thrombomodulin on the surface of endothelium. EPCR augments protein C activation by binding protein C and presenting it to the thrombin-thrombomodulin activation complex. Activated protein C (APC) retains its ability to bind EPCR, and this complex appears to be involved in some of the cellular signalling mechanisms that down-regulate inflammatory cytokine formation (TNF, IL-6). EPCR is shed from the vasculature by inflammatory mediators and thrombin. EPCS binds to activated neutrophils in a process that involves proteinase 3 and Mac-1. EPCR can undergo translocation from the plasma membrane to the nucleus.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.