TFPIalpha and TFPIbeta
TFPIα 和 TFPIβ
基本信息
- 批准号:6810297
- 负责人:
- 金额:$ 34.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-07-15 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:RNA splicingbinding proteinsbiological signal transductioncell membraneclinical researchcoagulation factor VIIcoagulation factor Xdiabetes mellitusenzyme activityflow cytometrygene expressiongenetically modified animalsglycosylphosphatidylinositolshuman subjectlaboratory mousemembrane proteinsparoxysmal nocturnal hemoglobinuriaprotein bindingprotein degradationprotein localizationprotein metabolismprotein structure functionsolubilitythromboplastintissue /cell culture
项目摘要
DESCRIPTION (provided by applicant): Tissue factor pathway inhibitor (TFPI) is the in vivo inhibitor of factor VIIa/tissue factor-induced coagulation and, as such, plays a critical physiologic role in regulating the coagulant and inflammatory effects of factor VIIa/tissue factor action. We have recently shown that two forms of the TFPI protein, produced by alternative mRNA splicing, are expressed in human cells. Both forms associate with the surface of cells in a glycosylphosphatidylinositol (GPI)-anchored fashion, but through different mechanisms. TFPI-alpha, a soluble protein, appears to bind to another GPI-anchored protein(s), whereas TFPI-beta contains an intrinsic GPI-anchor. The thrust of this proposal is to characterize and contrast the location, functional activity, and potential physiologic roles of TFPI-alpha and TFPI-beta. In our specific aims we propose to: 1) Compare the expression of TFP-alpha and TFPI-beta; 2) Determine the structural components of TFPR-alpha that mediate its cell surface binding; 3) Identify and characterize the TFPI-alpha surface binding protein(s); 4) Compare the activities of cell-surface TFPI-alpha and TFPI-beta, and soluble TFPI-alpha; and 5) Investigate the in vivo relevance of TFPI GPI-anchorage.
描述(由申请人提供):组织因子途径抑制剂(TFPI)是因子VIIa/组织因子诱导的凝血的体内抑制剂,因此在调节因子VIIa/组织因子作用的凝血和炎症作用中发挥关键的生理作用。我们最近表明,通过选择性 mRNA 剪接产生的两种形式的 TFPI 蛋白在人类细胞中表达。两种形式都以糖基磷脂酰肌醇 (GPI) 锚定的方式与细胞表面相关,但机制不同。 TFPI-α 是一种可溶性蛋白,似乎与另一种 GPI 锚定蛋白结合,而 TFPI-β 则含有内在的 GPI 锚定蛋白。该提案的主旨是描述和对比 TFPI-α 和 TFPI-β 的位置、功能活动和潜在生理作用。在我们的具体目标中,我们建议:1)比较TFP-α和TFPI-β的表达; 2) 确定介导其细胞表面结合的TFPR-α的结构成分; 3) 识别并表征 TFPI-α 表面结合蛋白; 4) 比较细胞表面TFPI-α和TFPI-β以及可溶性TFPI-α的活性; 5) 研究 TFPI GPI 锚固的体内相关性。
项目成果
期刊论文数量(0)
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GEORGE J BROZE其他文献
GEORGE J BROZE的其他文献
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