Tissue Factor–Factor VIIa Signaling

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Inhibitors of Factor VIIa/tissue factor.

The formation of the proteolytic complex composed of the serine protease Factor VIIa and the cell-associated glycoprotein tissue factor (FVIIa/TF) initiates a cascade of amplified zymogen activation reactions leading to thrombus formation. The critical role of the coagulation cascade in pathological thrombosis has been the basis for significant efforts to design selective inhibitors of the prot...

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Engineering of substrate selectivity for tissue factor.factor VIIa complex signaling through protease-activated receptor 2.

The complex of factor VIIa (FVIIa) with tissue factor (TF) triggers coagulation by recognizing its macromolecular substrate factors IX (FIX) and X (FX) predominantly through extended exosite interactions. In addition, TF mediates unique cell-signaling properties in cancer, angiogenesis, and inflammation that involve proteolytic cleavage of protease-activated receptor 2 (PAR2). PAR2 is cleaved b...

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Modulation of tissue factor-factor VIIa signaling by lipid rafts and caveolae.

OBJECTIVE Coagulation factor VIIa (VIIa) binding to its cellular receptor, tissue factor (TF), not only initiates the coagulation cascade but also induces cell signaling by activating G-protein coupled protease-activated receptors. The objective of the present study is to investigate the role of lipid rafts and caveolae in modulating TF-VIIa signaling and coagulant functions. METHODS AND RESU...

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Binding of factor VIIa to tissue factor permits rapid antithrombin III/heparin inhibition of factor VIIa.

Because free factor VIIa is inactivated only very slowly by a plasma concentration of antithrombin III (AT III) even in the presence of heparin, it has been assumed that AT III plays no significant role in regulating the initiation of tissue factor-dependent blood coagulation. However, in the present study, we present evidence that factor VIIa bound to tissue factor, unlike free factor VIIa, is...

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Structural biology of factor VIIa/tissue factor initiated coagulation.

Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C-terminal protease domain. Activation of FVII results in a two-chain FVIIa molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain (protease domain) held together by a single disulfide bond. During coagulation, the com...

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ژورنال

عنوان ژورنال: Arteriosclerosis, Thrombosis, and Vascular Biology

سال: 2005

ISSN: 1079-5642,1524-4636

DOI: 10.1161/01.atv.0000151624.45775.13