Orchestration of coagulation protease signaling by tissue factor.
Protease-activated receptors (PARs) are vascular sensors for signaling of the trypsinlike coagulation serine proteases that play key roles in cardiovascular medicine. In the initiation phase of coagulation, tissue factor (TF) orchestrates the assembly of VIIa with substrate X, forming a ternary complex in which product Xa is generated. The resulting TF-VIIa-Xa complex is an efficient activator of PAR1 and PAR2. TF initiation of the coagulation cascade is thus intimately linked to inflammatory cell signaling. Inflammation is an increasingly appreciated component of the vulnerable atherosclerotic plaque. Targeting inflammatory cell signaling events of the coagulation system may become an important aspect of efforts to improve antithrombotic therapy.
Riewald
Matthias
M
Department of Immunology C204, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ruf
Wolfram
W
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D001665:Binding Sites; D001779:Blood Coagulation Factors / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009363:Neoplasm Proteins; D011485:Protein Binding; D011487:Protein Conformation; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism*; D013925:Thromboplastin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D001779:Blood Coagulation Factors; D009363:Neoplasm Proteins; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant