INFORMATION SIGNALING PATHWAYS IN THE VASCULATURE

本申请建议深入研究炎症和炎症因子在炎症中的作用， 血管生成受体在血管系统内的信号传导过程， 将五个互动项目与四个核心的支持相结合， 了解多肽介导的信号通路 生长因子和细胞因子。这些项目 包括八名调查员之间合作研究努力 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的机制 分泌途径，（2）脂蛋白、蛋白酶和 极低密度脂蛋白受体蛋白酶抑制剂复合物 及其受体相关蛋白拮抗剂，（3）调节 通过蛋白酪氨酸磷酸酶的受体酪氨酸激酶信号传导，（4） 前列腺素介导的血管病理学机制 环氧合酶-1基因的表达，和（5）功能性 一种新的由丝裂原诱导蛋白编码的蛋白激酶的鉴定 基因这些互动研究工作将得到一个 提供后勤和业务支助的行政核心， 蛋白质和核酸化学核心，实验病理学核心 以及免疫学核心，提供这些领域的专业知识。这 应用程序的发展，从一个非常富有成效的NHLBI SCOR的努力， 输血医学，其中许多互动合作， 创造预计这些贡献来自研究 和支持的努力将产生新的见解的分子 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.