Immunological and functional analyses of the extracellular domain of human tissue factor
Abstract
Tissue factor (TF) initiates the extrinsic pathway of blood coagulation via formation of an enzymatic complex with coagulation factor VII/VIIa (FVII/VIIa). Although FVII is the only known ligand for TF, several reports in recent years have shown that the function of TF may not be limited to serving as a trigger of coagulation but that TF could also play a role in cellular signaling, metastasis, adhesion and embryogenesis. To explore the loci of the extracellular domain of TF important for its function, we analyzed the functional and immunological epitopes of TF1-219 by the use of both E. coli expressed TF variants encompassing various portions of the extracellular domain of TF and different anti-TF monoclonal antibodies (mAbs). N- and C-terminally truncated TF variants were analyzed for their VIIa-dependent procoagulant activity (PCA). The results obtained are in agreement with previously performed mutant and structural analyses of the interaction of FVII/FVIIa with the extracellular domain of TF. In addition, we observed that combination of two TF variants, Ec-TF1-122 and Ec-TF120-219, yields a soluble and active two-chain TF molecule with remarkable PCA. The reaction patterns of anti-TF mAbs with truncated TF variants and syn...Continue Reading
References
The crystal structure of the extracellular domain of human tissue factor refined to 1.7 A resolution
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