SIGNALING THROUGH CELL SURFACE RECEPTORS ON ENDOTHELIAL CELLS

这项研究的目的是了解内皮细胞的分子基础， 对外部事件的反应，包括局部损伤和炎症。 为了实现这一目标，我们将继续对两组细胞进行研究， 可以启动细胞内信号传导的表面受体， 内皮细胞：蛋白酶激活受体（PARs）和Eph 激酶。蛋白酶激活受体是G蛋白的一个亚家族 通过受体的蛋白水解激活的偶联受体， 通过受体N-末端的蛋白水解被激活。的四名成员 这个家庭的身份已经确认Eph激酶受体是一种 膜结合酪氨酸激酶的大家族，其配体也 细胞表面蛋白这两个受体家族都被选中 因为它们与内皮细胞生长和功能相关。 蛋白酶激活受体由于其在介导 对蛋白水解酶的反应， 在损伤和炎症部位的浓度。Eph受体是 基于它们在细胞间作用的假设而选择 内皮细胞、白细胞和血小板之间的相互作用， 以及介导内皮细胞之间的相互作用。是我们 相信这些受体家族在表面活性方面的比较 表达和分布，启动的信号通路， 通过受体激活，受体之间的串扰和适应， 包括流动和剪切力的变化， 提供深入了解内皮细胞生物学和病理学的水平， 组织的力量超越了集中在任何一个 受体家族事实上，这是将三个部分结合在一起的主题 并将其与其他4项提案联系起来， 计划项目，其中每一个都涉及内皮细胞的反应， 细胞、平滑肌细胞或血小板对它们的局部 环境通过细胞表面受体或整合素。

The goal of this to understand the molecular basis for endothelial cell responses to external events, including local injury and inflammation. To accomplish this we will continue our work on two groups of cell surface receptors that can initiate intracellular signaling in endothelial cells: the protease-activated receptors (PARs) and Eph kinases. The protease-activated receptors are a subfamily of G protein coupled receptors that are activated by proteolysis of the receptor that are activated by proteolysis of the receptor N-terminus. Four members of this family have been identified to date. Eph kinase receptors are a large family of membrane-bound tyrosine kinases whose ligands are also cell surface proteins. Both of these receptors families was chosen because of their relevance to endothelial cell growth and function. Protease-activated receptors because of their role in mediating responses to the proteolytic enzymes that accumulate at high concentrations at sites of injury and inflammation. Eph receptors were selected based upon the hypothesis that they play a role in cell-cell interactions between endothelial cells, leukocytes and platelets, as well as mediating interactions between endothelial cells. It is our belief that comparisons among these receptor families in term of surface expression and distribution, the signaling pathways that are initiated by receptor activation, crosstalk between the receptors and adaptations to the local environment including changes in flow and shear, will provide insights into endothelial cell biology and pathology at a level of organization beyond that which comes from concentration on any one receptor family. This is, in fact, the theme that unites the three parts of this proposal-and relates it to the other 4 proposals within this program project, each of which deals with the responses of endothelial cells, smooth muscle cells or platelets to changes in their local environment via cell surface receptors or integrins.