INFORMATION SIGNALING PATHWAYS IN THE VASCULATURE

这项应用建议深入研究炎症和炎症的作用 血管生成受体在血管内的信号传递过程和 将五个交互式项目与四个核心的支持相结合，以 了解多肽介导的信号转导途径 中胚层来源细胞中的生长因子和细胞因子。这些项目 包括八名研究人员之间合作研究工作 对血管壁功能的细胞和分子生物学感兴趣 这些包括：(1)成纤维细胞生长因子-1的作用机制 分泌途径，(2)脂蛋白、蛋白水解酶和 极低密度脂蛋白受体介导的蛋白酶抑制物复合体 及其受体相关蛋白拮抗剂，(3)调节 蛋白酪氨酸磷酸酶介导的受体酪氨酸激酶信号转导 利用转基因技术研究前列腺素介导的血管病理机制 环氧合酶-1基因的表达，以及(5)功能性 一种新的有丝分裂原诱导型蛋白激酶的特性 吉恩。这些互动研究工作将得到一个 提供后勤和运营支持的行政核心，以及 蛋白质与核酸化学核心--实验病理学核心 以及一个免疫学核心，提供这些领域的专业知识。这 应用程序是由高效的NHLBI SCOR在 输血医学，其中有许多互动合作 已创建。预计来自研究的贡献 支持的努力将产生对分子的新见解 负责调节血管病理的机制。

This application proposes to study in depth the role of inflammatory and angiogenic receptor signaling processes within the vasculature and combines five interactive projects with the support of four cores to achieve an understanding of signaling pathways mediated by polypeptide growth factors and cytokines in mesoderm-derived cells. These projects include collaborative research efforts between eight investigators interested in the cell and molecular biology of vessel wall function and these include, (1) the mechanism of the fibroblast growth factor-1 secretion pathway, (2) the catabolism of lipoproteins, protease and protease-inhibitor complexes by the very low density lipoprotein receptor and its receptor-associated protein antagonist, (3) the regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases, (4) mechanisms of prostanoid-mediated vascular pathology utilizing transgenic expression of the cyclooxygenase-1 gene, and (5) the functional characterization of a novel protein kinase encoded by a mitogen-inducible gene. These interactive research efforts will be supported by an administrative core to provide logistics and operational support and a protein and nucleic acid chemistry core, an experimental pathology core and an immunology core to provide expertise in these areas. This application evolved from the efforts of a very productive NHLBI SCOR in Transfusion Medicine from which numerous interactive collaborations were created. It is anticipated that the contributions derived from research and support efforts will generate new insight into the molecular mechanisms responsible for the regulation of vascular pathology.