FAK SIGNALING IN VASCULAR INJURY

血管损伤中的 FAK 信号传导

• 批准号: 6054965
• 负责人: LEWIS H ROMER
• 金额: $ 1.36万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-11-24 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6054965
• 关键词: biological signal transduction; bromodeoxyuridine; cell cell interaction; cell cycle; cell growth regulation; cell motility; cell proliferation; cellular pathology; confocal scanning microscopy; cord blood; cyclins; cytoskeletal proteins; cytotoxicity; embryogenesis; enzyme activity; fluorescence resonance energy transfer; focal adhesion kinase; gene expression; human tissue; membrane proteins; neoplastic cell; protein protein interaction; transfection; vascular endothelium; video microscopy

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.

FAK (pp125FAK) 是参与细胞基质粘附的主要信号蛋白。 拟议的研究探讨了 FAK 在细胞对血管损伤的反应中的作用。 第一个具体目标是确定 FAK 调节内皮细胞运动的机制。 共聚焦和视频显微镜以及 FAK 绿色荧光蛋白构建体将用于跟踪 FAK 动态和内皮细胞迁移。 FAK 过度表达和显性失活 FAK 的影响将在运动测定中定义。 第二个具体目标是阐明 FAK 信号传导至细胞核以调节内皮细胞增殖的途径。 FAK 信号传导将通过外源 FAK 变体和潜在下游信号传导蛋白的表达来操纵。 将评估细胞的溴脱氧尿苷掺入和细胞周期蛋白 D1 表达的变化。 拟议项目中的体外模型将使我们能够定义 FAK 信号传导的分子操纵对炎症性血管损伤的细胞反应的上述每个组成部分的影响。