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: 3196547
• 负责人: MICHAEL J. GETZ
• 金额: $ 19.06万
• 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 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3196547
• 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生性疾病经常是 与血液凝血的畸变有关。分子基础 这是很少的理解，但可能涉及增长之间的联系 调节机制和调节止血的机制。这项研究 试图通过建立功能来进一步定义这种链接 与人组织有关的新鉴定的小鼠蛋白的意义 因子，一种负责启动蛋白酶的细胞表面受体 级联导致血液凝血。此的氨基酸序列 从最初的cDNA克隆的核苷酸序列推导蛋白质 根据肽生长的诱导表达选择 因子刺激的小鼠成纤维细胞。对此序列的分析表明 该克隆代表鼠组织因子或第一个已知的因子 同源蛋白的示例。这项研究的主要目标 建议是确定该蛋白在功能上是否等效 到组织因子，如果是的，则确定两者是同源的还是 相关基因的产物。此外，这项研究将探索 该蛋白与生长相关的可能性多功能 与止血无关的特性。这些目标将实现， 部分结合了分子和免疫学方法 建立小鼠蛋白表达与 促凝活性和其他特定的表型改变 对肽生长因子的反应。