Cellular consequences upon factor VIIa binding to tissue factor.
Tissue factor (TF) is a cell-surface-bound glycoprotein that binds the zymogen, factor (F) VII, and the active serine protease, FVIIa. The FVIIa/TF complex is the major activator of coagulation in vivo. Under normal physiological conditions, TF is expressed only on extravascular sites and perivascularly in the adventitial layer of blood vessels. Although not normally expressed by cells within the circulation, TF can be induced in monocytes and endothelial cells. Also, several malignant cells express high levels of TF. Recent reports have shown that FVIIa binding to TF can influence a number of biological functions, such as angiogenesis and cancer metastasis. TF also seems to play an important role in cell adhesion and migration. The intracellular signalling is independent of downstream activation of the blood coagulation cascade. FVIIa/TF seems to transduce signalling by two distinct mechanisms: one independent of the cytoplasmatic domain but dependent on the proteolytic activity of FVIIa, and one dependent on the cytoplasmatic domain of TF.
Department of Medical Sciences, Laboratory for Coagulation Research, University Hospital, Uppsala, Sweden. agneta.siegbahn@klinikem.uas.lul.se
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D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D017434:Protein Structure, Tertiary; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000378:metabolism; D015398:Signal Transduction; D013925:Thromboplastin / Q000737:chemistry / Q000378:metabolism*
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D013925:Thromboplastin; D015942:Factor VIIa; C112908:protease-activated receptor 4