MECHANISM OF ACTION OF EPIDERMAL GROWTH FACTOR

本计划项目的基本目标是巩固增长研究 因子酪氨酸激酶信号转导途径，并利用广泛的 一系列的技术和智力技能，以实现这一目标。 的 表皮生长因子（EGF）是一种重要的细胞因子。 血小板衍生生长因子（PDGF）系统被包括用于比较 不同的信息。 在这些拟议的研究中， 基本的信号转导途径有待探索。 不同 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。 作为这些信号转导途径中的第一个要素， 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 探索阿尔法个体在反应产生上的生理差异 和β PDGF受体。 酪氨酸激酶底物构成第二个 细胞内的信号通路的步骤，该计划包括三个 探索磷脂酶C-γ 1（PLC-γ 1）的不同项目，以及 作为其他酪氨酸激酶底物。 项目2将使用生物化学和， 在较小程度上，生物物理方法来探索PLC-γ 1激活 EGF受体 最后，两个项目将探索更远的 这条路的元素。 项目5将使用生物化学方法， 研究生长因子激活丝氨酸激酶，酪蛋白激酶II和项目 8将使用分子生物学技术来研究生长因子 转录因子的激活。 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，但重点和综合系统的实验 方法将通过计划项目独特地提供。

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.