The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?
Tissue factor, a 47 kDa membrane glycoprotein, lies at the basis of the extrinsic pathway of the coagulation cascade. Interaction of TF with factor VIIa results in the formation of fibrin from fibrinogen, thereby inducing the formation of a blood clot. In addition to this well-established role in blood coagulation, TF is associated with various other physiological processes such as sepsis, inflammation, angiogenesis, metastasis and atherosclerosis. The molecular basis of the latter events is slowly emerging. It has become clear that TF-FVIIa interaction elicits a variety of intracellular signalling events that may be implicated in these actions. These events include the sequential activation of Src-like kinases, MAP kinases, small GTPases and calcium signalling. How this progress in the understanding of TF associated signal transduction may generate answers as to the mechanism through which TF exerts it pleiotropic effects will be focus of this review.
Versteeg
H H
HH
Laboratory for Experimental Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands. h.h.versteeg@amc.uva.nl
Peppelenbosch
M P
MP
Spek
C A
CA
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001777:Blood Coagulation / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000503:physiopathology; D015942:Factor VIIa / Q000494:pharmacology / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008074:Lipoproteins / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D010215:Papio; D010586:Phagocytes / Q000378:metabolism; D018805:Sepsis / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*; D013925:Thromboplastin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology
D016207:Cytokines; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D019061:src-Family Kinases; D015942:Factor VIIa; D020558:GTP Phosphohydrolases