MECHANISM OF ACTION OF EPIDERMAL GROWTH FACTOR

该计划项目的基本目标是巩固对增长的研究 因子酪氨酸激酶信号转导途径及其广泛的利用 实现这一目标的一系列技术和智力技能。这个 基本的焦点是表皮生长因子(EGF)系统，但对 包括血小板衍生生长因子(PDGF)系统，以进行比较 和独特的信息。在这些拟议的研究中，有几个要素 基本的信号转导途径有待探索。不同的 项目利用生物化学、细胞生物学、组织学、分子生物学、 和生物物理学作为实验技术。 因为这些信号转导通路中的第一个元素是生长 因子受体，项目7将使用生物物理方法来探索EGF- 受体相互作用和项目4将利用细胞生物学方法 探索阿尔法反应产生的生理差异 和β-PDGF受体。酪氨酸激酶底物构成第二种 信号通路中的细胞内步骤，该计划包括三个 探索磷脂酶C-Gamma1(PLC-Gamma1)的不同项目 和其他酪氨酸激酶底物一样。项目2将使用生化和， 在较小程度上，探索PLC-Gamma1激活的生物物理方法 通过EGF受体。最后，两个项目将探索更远的 这条途径的要素。项目5将使用生化方法来 一种生长因子激活的丝氨酸激酶、酪蛋白激酶II及项目研究 8号将利用分子生物学技术研究生长因子 转录因子的激活。 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，但重点突出且集成的实验系统 方法将通过计划项目独一无二地提供。

The basic goal of this Program Project is to consolidate studies of growth factor tyrosine kinase signal transduction pathways and to utilize a broad range of technological and intellectual skills to realize this goal. The basic focus is the epidermal growth factor (EGF) system, but studies of the platelet-derived growth factor (PDGF) system are included for comparative and distinct information. In these proposed studies, several elements of the basic signal transduction pathway are to be explored. The different projects utilize biochemistry, cell biology, histology, molecular biology, and biophysics as experimental techniques. As the first element in these signal transduction pathways is the growth factor receptors, Project 7 will use biophysical methods to explore EGF- receptor interactions and project 4 will utilize cell biological approaches to explore physiological differences in response generation by the alpha and beta PDGF receptors. Tyrosine kinase substrates constitute the second intracellular step in the signaling pathways and the Program includes three distinct projects to explore phospholipase C-gamma1 (PLC-gamma1), as well as other tyrosine kinase substrates. Project 2 will use biochemical and, to a lesser extent, biophysical approaches to explore PLC-gamma1 activation by the EGF receptor. Finally, two projects will explore more distal elements of this pathway. Project 5 will use biochemical approaches to study a growth factor-activated serine kinase, casein kinase II and Project 8 will use molecular biological techniques to investigate the growth factor activation of transcription factors. 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 focused and integrated system of experimental approaches will be uniquely available through the Program Project.