GENETICS AND CELL PHYSIOLOGY OF MURINE TISSUE FACTOR

点击翻译按钮获取中文摘要

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.