GENETICS AND CELL PHYSIOLOGY OF MURINE TISSUE FACTOR

转移性癌症和某些其他增殖性疾病经常发生 与凝血异常有关。分子基础 人们对这一点知之甚少，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 寻求通过建立功能性联系来进一步定义这种联系 新发现的小鼠蛋白与人体组织相关的意义 因子，负责启动蛋白酶的细胞表面受体 级联反应导致血液凝固。该氨基酸序列 蛋白质最初是从cDNA克隆的核苷酸序列推导出来的 根据肽生长中的诱导表达进行选择 因子刺激的小鼠成纤维细胞。对该序列的分析表明 该克隆代表鼠组织因子或第一个已知的 同源蛋白质的例子。本研究的主要目标 建议是确定该蛋白质是否在功能上等效 组织因子，如果是，确定两者是否是同基因的或 相关基因的产物。此外，本研究将探讨 该蛋白质可能具有与生长相关的多功能性 与止血无关的特性。这些目标将会实现， 部分地，结合使用分子和免疫学方法 建立小鼠蛋白表达与 促凝血活性和其他特异性的表型改变 对肽生长因子的反应。

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.