Disulfide reduction abolishes tissue factor cofactor function
نویسندگان
چکیده
منابع مشابه
Tissue factor: molecular recognition and cofactor function.
One aspect of the inflammatory response is the activation of the coagulation protease cascade resulting from the expression of tissue factor (TF) on vascular cells. TF is the cell-surface receptor for the coagulation serine protease factor VIIa, providing cofactor function by "switching on" the catalytic site of the bound enzyme and by contributing to the assembly with macromolecular substrate....
متن کاملTissue factor coagulant function is enhanced by protein-disulfide isomerase independent of oxidoreductase activity.
Protein-disulfide isomerase (PDI) switches tissue factor (TF) from coagulation to signaling by targeting the allosteric Cys186-Cys209 disulfide. Here, we further characterize the interaction of purified PDI with TF. We find that PDI enhances factor VIIa-dependent substrate factor X activation 5-10-fold in the presence of wild-type, oxidized soluble TF but not TF mutants that contain an unpaired...
متن کاملDisulfide isomerization switches tissue factor from coagulation to cell signaling.
Cell-surface tissue factor (TF) binds the serine protease factor VIIa to activate coagulation or, alternatively, to trigger signaling through the G protein-coupled, protease-activated receptor 2 (PAR2) relevant to inflammation and angiogenesis. Here we demonstrate that TF.VIIa-mediated coagulation and cell signaling involve distinct cellular pools of TF. The surface-accessible, extracellular Cy...
متن کاملTissue factor activation: is disulfide bond switching a regulatory mechanism?
A majority of tissue factor (TF) on cell surfaces exists in a cryptic form (ie, coagulation function inactive) but retains its functionality in cell signaling. Recent studies have suggested that cryptic TF contains unpaired cysteine thiols and that activation involves the formation of the disulfide bond Cys186-Cys 209 and that protein disulfide isomerase (PDI) regulates TF coagulant and signali...
متن کاملTissue Factor Structure and Function
Tissue factor (TF) is an integral membrane protein that is essential to life. It is a component of the factor VIIa-TF complex enzyme and plays a primary role in both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed to blood and binds plasma factor VIIa, and the resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing....
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ژورنال
عنوان ژورنال: Biochimica et Biophysica Acta (BBA) - General Subjects
سال: 2013
ISSN: 0304-4165
DOI: 10.1016/j.bbagen.2013.02.013