GENETICS AND CELL PHYSIOLOGY OF MURINE TISSUE FACTOR

鼠组织因子的遗传学和细胞生理学

• 批准号: 3196546
• 负责人: MICHAEL J. GETZ
• 金额: $ 18.25万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3196546
• 关键词: antibody formation; blood coagulation disorders; clone cells; complementary DNA; cycloheximide; epidermal growth factor; fibroblast growth factor; hemostasis; laboratory mouse; messenger RNA; nucleic acid sequence; peptides; physiology; polymerase chain reaction; protein biosynthesis; protein structure function; transfection

Metastatic cancer and certain other proliferative diseases are frequently associated with aberrations of blood coagulation. The molecular basis for this is poorly understood but may involve a linkage between growth regulatory mechanisms and those that regulate hemostasis. This research seeks to further define such a link by establishing the functional significance of a newly identified mouse protein related to human tissue factor, a cell surface receptor responsible for initiating the protease cascade leading to blood coagulation. The amino acid sequence of this protein was deduced from the nucleotide sequence of cDNA clones originally selected on the basis of inducible expression in peptide growth factor-stimulated mouse fibroblasts. An analysis of this sequence indicates that this clone represents either murine tissue factor or the first known example of an homologous protein. The major objective of this research proposal is to determine whether this protein is functionally equivalent to tissue factor, and if so, to determine whether the two are isogenic or the products of related genes. In addition, this research will explore the possibility that this protein is multifunctional with growth-associated properties unrelated to hemostasis. These objectives will be accomplished, in part, using a combination of molecular and immunological approaches to establish the relationship between expression of the mouse protein and phenotypic alterations in procoagulant activity and other specific responses to peptide growth factors.

转移性癌症和某些其他增殖性疾病通常是 与凝血异常有关的分子基础 人们对此知之甚少， 调节机制和调节止血的机制。本研究 试图通过建立函数来进一步定义这种联系， 一种新发现小鼠组织相关蛋白的意义 因子，细胞表面受体，负责启动蛋白酶 级联导致血液凝固。这个的氨基酸序列 蛋白质最初是从cDNA克隆的核苷酸序列推导出来的 基于肽生长中的诱导表达选择 因子刺激的小鼠成纤维细胞。对该序列的分析表明 这个克隆要么代表鼠组织因子，要么代表第一个已知的 同源蛋白质的例子。本研究的主要目的是 建议是确定这种蛋白质是否在功能上等效 组织因子，如果是这样，以确定两者是否是同源的， 相关基因的产物。此外，本研究还将探讨 这种蛋白质可能是多功能的生长相关的 与止血无关的性质。这些目标将会实现， 在某种程度上，使用分子和免疫学方法的组合， 建立小鼠蛋白质表达与 促凝血活性和其他特异性表型改变 对肽生长因子的反应。