FAK SIGNALING IN VASCULAR INJURY

FAK （pp125FAK）是参与细胞-基质粘附的主要信号蛋白。提出的研究考察了FAK在血管损伤的细胞反应中的作用。第一个具体目标是确定FAK调节内皮细胞运动的机制。共聚焦显微镜和视频显微镜以及FAK-绿色荧光蛋白结构将用于跟踪FAK动力学和内皮细胞迁移。FAK过表达和显性阴性FAK的影响将在运动测定中确定。第二个特定的目的是阐明FAK信号传导到细胞核的途径在内皮细胞增殖的调节。FAK信号将被外源FAK变体和潜在下游信号蛋白的表达所操纵。将评估细胞中溴脱氧尿苷掺入和细胞周期蛋白D1表达的变化。拟议项目中的体外建模将使我们能够定义FAK信号的分子操纵对炎症性血管损伤细胞反应的上述每个组成部分的后果。

FAK (pp125FAK) is a major signaling protein involved in cell- matrix adhesion. The proposed studies examine the role of FAK in cellular responses to vascular injury. The first specific aim is to define the mechanisms of FAK regulation of endothelial cell motility. Confocal and video microscopy and FAK-green fluorescent protein constructs will be used to track FAK dynamics and endothelial cell migration. The effects of FAK overexpression, and dominant negative FAK will be defined in motility assays. The second specific aim is to elucidate pathways of FAK signaling to the nucleus in the regulation of endothelial cell proliferation. FAK signaling will be manipulated by expression of exogenous FAK variants and of potential downstream signaling proteins. Cells will be evaluated for changes in bromodeoxyuridine incorporation and cyclin D1 expression. The in vitro modeling in the proposed project will allow us to define the consequences of the molecular manipulation of FAK signaling for each of the above components of cellular response to inflammatory vascular injury.