MECHANISM OF ACTION OF EPIDERMAL GROWTH FACTOR

该计划项目的长期目标是开发和利用 阐明细胞和分子的新实验方法 表皮生长因子(EGF)调节细胞的机制 扩散。该计划包含由经验丰富的人领导的研究项目 建议联合使用新技术和新系统的调查人员 已经为其开发了初步数据。所有的项目都是 以EGF受体为中心，并询问信号是如何由 分子，并传递到生物反应中。 项目1将使用分子生物学技术克隆和 鉴定EGF受体的磷酸化底物。这个项目 将使用类似的方法来识别 受EGF正向或负向控制。项目2将研究，与 生化和细胞生物学实验，其机制 EGF：受体复合体与肌醇磷酸途径通信。 这一途径的产物可能对细胞的调节作用 还将对增长控制进行调查。项目3将开发和开发 描述有关细菌生长调控的生物学信息 依赖EGF的上皮细胞系。这一细胞系将被 几个项目以不同的方式。项目4将研究监管 血小板衍生生长因子与表皮生长因子的相互作用 受体。项目5将开发关于增长的机制的数据 影响DNA拓扑异构酶活性的因素。项目6将雇用 用电子显微镜确定物质的分布和相互作用 在EGF途径的关键蛋白中。项目7将使用生物物理 定义细节的方法学，电子顺磁共振 EGF与受体的相互作用，这是其他方法无法获得的。这些 研究项目将得到两个核心单位的支持。一个核心将 提供准备和分析服务，而第二个核心将 提供集中的行政支持。 计划项目机制提供统一的工具，以最大限度地提高 集中专业资源，包括技术和智力资源， 调查人员为个人研究工作和 远景目标。调查人员之间的个人合作和 技术广泛，但以生物为重点的集成系统 试验性方法将通过该计划独一无二地提供 项目。

The long range objective of this Program Project is to develop and exploit new experimental approaches to elucidate the cellular and molecular mechanisms by which epidermal growth factor (EGF) regulates cell proliferation. The program contains research projects led by experienced investigators who propose to jointly utilize new technologies and systems for which preliminary data have been developed. All the projects are centered on the EGF receptor and ask how signals are received by this molecule and transmitted into biological responses. Project 1 will use molecular biological techniques to clone and characterize phosphorylation substrates of the EGF receptor. This project will employ similar methodologies to identify DNA sequences that are positively or negatively controlled by EGF. Project 2 will study, with biochemical and cell biological experiments, the mechanism by which EGF:receptor complexes communicate with the inositol phosphate pathway. The regulatory effects that the products of this pathway may have on cell growth control will also be investigated. Project 3 will develop and characterize biological information concerning growth regulation of an EGF-dependent epithelial cell line. This cell line will be utilized by several of the projects in different ways. Project 4 will study regulatory interactions between the platelet-derived growth factor and the EGF receptor. Project 5 will develop data on the mechanism by which growth factors affect the activity of DNA topoisomerases. Project 6 will employ electron microscopy to determine the physical distribution and interactions among key proteins in the EGF pathway. Project 7 will employ a biophysical methodology, electron paramagnetic resonance, to define details of EGF-receptor interactions that are not otherwise obtainable. These research projects will be supported by two core units. One core will provide preparative and analytical services, while the second core will provide centralized administrative support. The Program Project mechanism provides a unifying vehicle to maximize the concentration of specialized resources, both technical and intellectual, of the investigators for the benefit of individual research efforts and the long range goals. Personal collaborations among the investigators and a technically broad, but biologically focused and integrated system of experimental approaches will be uniquely available through the Program Project.