Protein C pathway

The protein-C pathway is one of the most important anticoagulant mechanisms. It is activated by thrombin. Thrombin binds to a cofactor in the membrane of endothelial cells, thrombomodulin (TM). TM bound thrombin no longer activates clotting factors or platelets but becomes an effective protein C (PC) activator. Activated PC (APC) forms a complex with Protein S, which inactivates FVIIIa and FVa. Hereby generation of Flla by the prothrombinase complex is inhibited (Fig. 9). Thus, the PC-pathway controls thrombin generation in a negative feedback manner. 

A type I transmembrane protein called endothelial cell protein C receptor (EPCR), which is expressed at high levels exclusively on a subset of endothelial cells, has also been identified. EPCR has a role in the protein C pathway (30). EPCR binds to both protein C and activated protein C (APC) with equal affinity. Activation of protein C presumably requires interaction of the protein C-EPCR complex with the thrombin-thrombomodulin complex. APC that is formed as a result of this interaction is reversibly bound to EPCR until it dissociates to react subsequently with protein S. The APC-protein S complex inactivates activated factor V (Va). 

Fig. 7. Our current understanding of the protein C pathway. V, and VIII, represent inactivated factors V and VIII, respectively. For an explanation of other abbreviations see text.

Dahlback, A. and Villotreix, B. 2005. The anticoagulant protein C pathway. FEBS Letters 579(15), 3310-3316. 

Di Cera E. Thrombin. Mol Aspects Med. 2008 29 203-254. Esmon CT. The protein C pathway. Chest 2003 124 26S-32S. ConghUn SR. Thrombin signalling and protease-activated receptors. Natnre 2000 407 258-264. 

The protein C pathway serves as a natural defence mechanism against thrombosis. Patients with severe sepsis have a very low concentration of activated protein C... 

Anticoaguiants Protein C pathway Tobacco Human protein C (seiaim protease) AMT 13... 

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