Blood clotting is initiated by the two-subunit enzyme consisting of the plasma protease, factor VIIa (the catalytic subunit), bound to the integral membrane protein, tissue factor (the regulatory subunit). Molecular dynamics simulations have predicted that certain residues in the tissue factor ectodomain interact with phosphatidylserine headgroups to ensure optimal positioning of the tissue fac...

The human coagulation system continuously generates very small quantities of Factor Xa and thrombin. Current evidence suggests that basal level activation of the hemostatic mechanism occurs via Factor VIIa-dependent activation of Factor X, but direct proof has not been available for the participation of tissue factor in this pathway. To examine this issue, we infused relatively high concentrati...

Timely correction of coagulopathy in patients with traumatic brain injury (TBI) improves mortality. Recombinant, activated factor VII (VIIa) has been identified as an effective method to correct coagulopathy in patients with TBI. We performed a retrospective study (January 1, 2008-December 31, 2009) of all patients with TBI and coagulopathy (international normalized ratio (INR) > 1.5) transfer...

Tissue factor (TF)/VIIa/protease‑activated receptor 2 (PAR2) has been shown to trigger the ERK1/2 signaling pathway. This was shown to be closely associated with the proliferation and migration of SW620 colon cancer cells; however, the detailed mechanisms remain unclear. The aim of the present study was to elucidate the effects of calcium signaling on the proliferation and migration of SW620 ce...

The activation of prothrombin, factor V, factor VIII, factor IX, and factor X by the tissue factor-factor VIIa complex, in vitro, in a system in which each precursor protein was present at plasma concentration, was evaluated using a combination of activity assays, immunoblots, active-site blots, and autoradiography. The thrombin generation curves observed were distinctly nonlinear and typically...

BACKGROUND Tissue factor (TF) and/or active factor (F)VIIa may be stored inside resting platelets. OBJECTIVES The objective of this study was to examine if platelets, following activation of GPVI, could support tenase and prothrombinase activity without any exogenously added tissue factor. METHODS Thrombin (IIa) formation on gel-filtered platelets with added factors or the clotting of plate...

Tissue factor (TF), apart from activating the extrinsic pathway of the blood coagulation, is a principal regulator of embryonic angiogenesis and oncogenic neoangiogenesis, but also influences inflammation, leukocyte diapedesis and tumor progression. The intracellular domain of TF lacks homology to other classes of receptors and hence the signaling mechanism is poorly understood. Here we demonst...