title: TFPI-dependent activities of protein S.
abstract: Protein S is an essential anticoagulant protein that acts as a cofactor for full length tissue factor pathway inhibitor (TFPI) and activated protein C (APC) in the down regulation of coagulation. Protein S enhances APC-mediated inactivation of the coagulation factors Va and VIIIa, and it stimulates inhibition of factor (F)Xa by TFPI. Because TFPI is a tight binding, but slow inhibitor of FXa, the TFPI/protein S system fails to regulate FXa generation at high tissue factor/FVIIa concentrations. In this review, we explain how TFPI/protein S can regain its activity at high tissue factor concentrations in the presence of APC, resulting in an intertwinement of TFPI- and APC-cofactor activities of protein S, and making TFPI a major determinant of APC-anticoagulant activity in plasma.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University Maastricht, The Netherlands.
authors.forename: Sameera
authors.initials: S
authors.lastname: Peraramelli
authors.forename: Jan
authors.initials: J
authors.lastname: Rosing
authors.forename: Tilman M
authors.initials: TM
authors.lastname: Hackeng
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D017293:Protein S / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D008074:Lipoproteins; D017293:Protein S; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D013917:Thrombin