FAK SIGNALING IN VASCULAR INJURY

FAK(Pp125FAK)是参与细胞-基质黏附的主要信号蛋白。这项拟议的研究考察了FAK在细胞对血管损伤的反应中的作用。第一个具体目的是明确FAK对内皮细胞运动的调节机制。共聚焦显微镜和视频显微镜以及FAK-绿色荧光蛋白构建将被用于跟踪FAK的动力学和内皮细胞的迁移。FAK过表达和显性阴性FAK的影响将在动力分析中确定。第二个具体目的是阐明FAK信号通路在调控内皮细胞增殖中的作用。FAK信号将通过外源FAK变异体和潜在的下游信号蛋白的表达来操纵。将评估细胞溴脱氧尿嘧啶核苷掺入和细胞周期蛋白D1表达的变化。建议项目中的体外建模将使我们能够确定FAK信号的分子操作对炎性血管损伤的上述细胞反应的每个组成部分的影响。

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.