ROLE OF CELL SURFACE IN REGULATING CELL PROLIFERATION

该项目旨在确定分子间的相互作用， 与调节细胞分裂的起始有关。 我们的两个主要 目的是确定胰岛素和表皮生长的作用部位 因子，并定义在凝血酶结合到其上之后发生的事件。 受体参与细胞分裂的起始。 我们先前已经 显示凝血酶在细胞表面作用足以启动细胞 这种分裂需要凝血酶占据特定的细胞 表面受体 我们建议使用类似的固定技术， 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。 若干条证据 这表明凝血酶蛋白水解切割其自身受体作为 有丝分裂信号 因此，我们正在努力了解促有丝分裂 凝血酶与其受体之间的相互作用（1）通过分离和 表征凝血酶受体，和（2）通过制备荧光 凝血酶的衍生物，以显示它们与凝血酶受体的结合， 确定诸如受体重新分布的事件是否是凝血酶 启动细胞分裂

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.