GENETICS AND CELL PHYSIOLOGY OF MURINE TISSUE FACTOR

转移性癌症和某些其他增生性疾病经常 与凝血功能异常有关。基因的分子基础 人们对此知之甚少，但可能涉及到增长与 调节机制和那些调节止血的机制。这项研究 寻求通过建立功能性的 一种新发现的与人体组织相关的小鼠蛋白的意义 因子，一种负责启动蛋白酶的细胞表面受体 导致血液凝固的级联反应。它的氨基酸序列 蛋白质最初是从cdna克隆的核苷酸序列推导出来的。 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。对这一序列的分析表明 这个克隆要么代表了小鼠组织因子，要么代表了第一个已知的 同源蛋白质的例子。这项研究的主要目的 建议是确定这种蛋白质在功能上是否相同 组织因子，如果是这样的话，以确定这两个是同基因还是 相关基因的产物。此外，这项研究还将探索 这种蛋白可能是多功能的，与生长相关 与止血无关的特性。这些目标将会实现， 在一定程度上，使用分子和免疫学方法的组合来 建立小鼠蛋白的表达与基因表达的关系 促凝血活性和其他特异性的表型改变 对多肽生长因子的反应。

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.