ROLE OF CELL SURFACE IN REGULATING CELL PROLIFERATION

细胞表面在调节细胞增殖中的作用

• 批准号: 3227605
• 负责人: Darrell H. Carney
• 金额: $ 10.53万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227605
• 关键词: affinity chromatography; autoradiography; cell growth regulation; cell membrane; dexamethasone; electron microscopy; epidermal growth factor; flow cytometry; fluorescence microscopy; growth factor; human tissue; insulin; membrane activity; radiotracer; thrombin; tissue /cell culture

This project is aimed at determining the molecular interactions which are causally involved in regulating initiation of cell division. Our two primary objectives are to determine the site of action of insulin and epidermal growth factor and to define events which occur subsequent to thrombin binding to its receptor which are involved in initiation of cell division. We have previously shown that thrombin action at the cell surface is sufficient to initiate cell division and that this division requires thrombin occupancy of specific cell surface receptors. We propose to use similar techniques of immobilization and quantitation of released material to determine whether cell surface action of non-proteolytic peptide factors such as insulin and epdermal growth factor is also sufficient to generate a mitogenic signal. Several lines of evidence indicate that thrombin proteolytically cleaves its own receptor as a part of the mitogenic signal. Therefore, we are working toward understanding the mitogenic interaction between thrombin and its receptor (1) by isloating and characterizing the thrombin receptor, and (2) by preparing fluorescent derivatives of thrombin to visualize their binding to thrombin receptors and to determine if events such as receptor redistributions are necessary for thrombin to initiate cell division.

该项目旨在确定分子相互作用 因果地参与调节细胞分裂的启动。 我们的两个主要 目的是确定胰岛素的作用部位和表皮生长 因子并定义凝血酶与其结合后发生的事件 参与细胞分裂起始的受体。 我们之前有过 研究表明，细胞表面的凝血酶作用足以启动细胞 分裂并且这种分裂需要凝血酶占据特定细胞 表面受体。 我们建议使用类似的固定技术和 定量释放的物质以确定细胞表面作用是否 非蛋白水解肽因子，如胰岛素和表皮生长因子 也足以产生促有丝分裂信号。 几行证据 表明凝血酶通过蛋白水解裂解其自身受体作为凝血酶的一部分 有丝分裂信号。 因此，我们正在努力了解促有丝分裂 凝血酶与其受体 (1) 之间通过隔离和相互作用相互作用 表征凝血酶受体，以及（2）通过制备荧光 凝血酶衍生物以可视化其与凝血酶受体的结合并 确定受体重新分布等事件对于凝血酶是否是必需的 启动细胞分裂。