NDLI: TISSUE FACTOR PATHWAY INHIBITOR: STRUCTURE-FUNCTION

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TISSUE FACTOR PATHWAY INHIBITOR: STRUCTURE-FUNCTION

Content Provider	PubMed Central
Author	Broze, George J. Girard, Thomas J.
Abstract	An inhibitor of tissue factor-induced coagulation was rediscovered in the 1980’s and subsequently named tissue factor pathway inhibitor (TFPI). Three isoforms of TFPI are transcribed through alternative mRNA splicing: TFPIα, which contains an acidic aminoterminus followed by three tandem Kunitz-type protease inhibitor domains and a basic carboxyterminus; TFPIβ, in which the Kunitz-3 and carboxyterminus of TFPIα are replaced with a different carboxyterminus containing a glycosyl phosphatidyl inositol (GPI) anchor; and TFPIδ, which is truncated following the Kunitz-2 domain. The microvascular endothelium is thought to be the principal source of TFPI and TFPIα is the predominant isoform expressed in humans. TFPIα, apparently attached to the surface of the endothelium in an indirect GPI-anchor-dependent fashion, represents the greatest in vivo reservoir of TFPI. The Kunitz-2 domain of TFPI is responsible for factor Xa inhibition and the Kunitz-1 domain is responsible for factor Xa-dependent inhibition of the factor VIIa/tissue factor catalytic complex. The anticoagulant activity of TFPI in one-stage coagulation assays is due mainly to its inhibition of factor Xa through a process that is enhanced by protein S and dependent upon the Kunitz-3 and carboxyterminal domains of full-length TFPIα. Carboxyterminal truncated forms of TFPI as well as TFPIα in plasma, however, inhibit factor VIIa/tissue factor in two-stage assay systems. Studies in gene-disrupted mice demonstrate the physiological importance of TFPI.
Starting Page	262
File Format	PDF
ISSN	10939946
Journal	Frontiers in bioscience : a journal and virtual library
Volume Number	17
Language	English
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

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