ROLE OF CELL SURFACE IN REGULATING CELL PROLIFERATION

这个项目的目的是确定分子间的相互作用 与调节细胞分裂的启动有因果关系。我们的两个初选 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 参与细胞分裂启动的受体。我们之前已经 表明凝血酶在细胞表面的作用足以启动细胞 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化技术和 对释放的物质进行定量，以确定细胞表面行为是否 胰岛素和表皮生长因子等非蛋白水解肽因子 也足以产生有丝分裂信号。有几条证据 表明凝血酶蛋白水解性地裂解它自己的受体，作为 有丝分裂信号。因此，我们正在努力了解有丝分裂原 凝血酶与其受体(1)的相互作用 表征凝血酶受体，以及(2)通过制备荧光 凝血酶的衍生物，以可视化其与凝血酶受体的结合并 确定凝血酶是否需要受体重分布等事件 以启动细胞分裂。

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.