MECHANISM OF ACTION OF EPIDERMAL GROWTH FACTOR

该项目的长期目标是开发和利用 新的实验方法来阐明细胞和分子 表皮生长因子（EGF）调节细胞生长的机制 增殖 该计划包含由经验丰富的领导的研究项目 研究人员提出共同利用新技术和新系统， 已经建立了初步数据。 项目全部 EGF的作用是什么？EGF的作用是什么？ 分子并转化为生物反应。 项目1将利用分子生物学技术克隆和 EGF受体的磷酸化底物。 这个项目 将采用类似的方法来识别DNA序列， EGF的作用是积极或消极的。 项目2将研究，与 生物化学和细胞生物学实验， EGF：受体复合物与磷酸肌醇途径沟通。 这一途径的产物对细胞的调节作用 还将研究生长控制。 项目3将开发和 表征有关生长调节的生物学信息， EGF依赖性上皮细胞系。 该细胞系将用于 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和EGF之间的相互作用 受体的 项目5将开发关于增长机制的数据， 影响DNA拓扑异构酶活性的因素。 项目6将采用 用电子显微镜测定物理分布和相互作用 EGF的主要作用机制 项目7将采用生物物理 方法学，电子顺磁共振，以确定细节 EGF-受体相互作用，否则无法获得。 这些 研究计划将由两个核心单位资助。 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。 计划项目机制提供了一个统一的工具，以最大限度地提高 集中专门资源，包括技术和知识， 研究人员为了个人研究工作的利益， 长期目标。 调查人员之间的个人合作， 技术上广泛，但生物重点和综合系统， 实验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.