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组织因子途径抑制剂：结构-功能。

Tissue factor pathway inhibitor: structure-function.

机构信息

Division of Hematology, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

Front Biosci (Landmark Ed). 2012 Jan 1;17(1):262-80. doi: 10.2741/3926.

DOI:10.2741/3926
PMID:22201743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3692300/
Abstract

TFPI is a multivalent, Kunitz-type proteinase inhibitor, which, due to alternative mRNA splicing, is transcribed in three isoforms: TFPIalpha, TFPIdelta, and glycosyl phosphatidyl inositol (GPI)-anchored TFPIbeta. The microvascular endothelium is thought to be the principal source of TFPI and TFPIalpha is the predominant isoform expressed in humans. TFPIalpha, 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 TFPIalpha. Carboxyterminal truncated forms of TFPI as well as TFPIalpha in plasma, however, inhibit factor VIIa/tissue factor in two-stage assay systems. Studies in gene-disrupted mice demonstrate the physiological importance of TFPI.

摘要

组织因子途径抑制物（TFPI）是一种多价的 Kunitz 型蛋白酶抑制剂，由于其 mRNA 剪接方式不同，转录成三种同工型：TFPIalpha、TFPIdelta 和糖基磷脂酰肌醇（GPI）锚定的 TFPIbeta。微血管内皮细胞被认为是 TFPI 的主要来源，TFPIalpha 是人类表达的主要同工型。TFPIalpha 似乎以间接的 GPI 锚定依赖方式附着在内皮细胞表面，是体内 TFPI 的最大储备库。TFPI 的 Kunitz-2 结构域负责抑制因子 Xa，Kunitz-1 结构域负责抑制因子 VIIa/组织因子催化复合物。在一步凝血测定中，TFPI 的抗凝活性主要归因于其通过蛋白 S 增强的因子 Xa 抑制作用，并且依赖全长 TFPIalpha 的 Kunitz-3 和羧基末端结构域。然而，血浆中的羧基末端截断形式的 TFPI 以及 TFPIalpha 在两步测定系统中抑制因子 VIIa/组织因子。基因敲除小鼠的研究表明 TFPI 在生理上的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/37111cc705e8/nihms480155f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/65fbaceb4629/nihms480155f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/9b914140b150/nihms480155f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/56b01f32a0bc/nihms480155f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/361afa3ab42f/nihms480155f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/21b2a94c2263/nihms480155f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/a19de5c56e03/nihms480155f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/76907108d83a/nihms480155f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/37111cc705e8/nihms480155f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/65fbaceb4629/nihms480155f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/9b914140b150/nihms480155f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/56b01f32a0bc/nihms480155f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/361afa3ab42f/nihms480155f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/21b2a94c2263/nihms480155f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/a19de5c56e03/nihms480155f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/76907108d83a/nihms480155f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b489/3692300/37111cc705e8/nihms480155f8.jpg

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