RECONSTITUTION OF GROWTH FACTOR RECEPTOR TYROSINE KINASE

生长因子受体酪氨酸激酶的重建

• 批准号: 2734612
• 负责人: RICHARD A. CERIONE
• 金额: $ 23.12万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734612
• 关键词: cell cell interaction; conformation; enzyme substrate; epidermal growth factor; fluorescence spectrometry; fluorescent dye /probe; gel electrophoresis; growth factor receptors; guanine nucleotide binding protein; heregulin; high performance liquid chromatography; human tissue; mitogen activated protein kinase; phospholipids; phosphorylation; protein reconstitution; protein structure function; protein tyrosine kinase; radionuclides; receptor expression; tissue /cell culture; vesicle /vacuole

DESCRIPTION (Adapted from the Investigator's Abstract): This application is a renewal of an RO1 to understand the mechanisms by which EGF receptor family members are activated and signal. The family of receptors includes the EGF receptor itself, Neu, ErbB3 and ErbB4. It is noted in the application that ligand binding to a particular receptor induces or stabilizes homo- or heterodimer formation. The properties of the latter are especially interesting but not particularly well known. The initial emphasis of the proposal is on complexes established between the ErbB3 and Neu and the EGF receptor and Neu. The first aim deals with mechanisms of activation, and specifically how ErbB3, which is not an effective tyrosine kinase, promotes activation of Neu upon binding heregulin, and whether Neu is activated at all by the EGF receptor. The answers to both will be achieved by reconstitution of purified normal or mutant proteins in phospholipid vesicles. The second aim addresses proximal signaling molecules. One hypothesis is that tyrosine phosphorylation of ErbB3 by Neu accounts for binding of ErbB3 to p85. Also to be examined is the mechanism by which the EGF receptor achieves phosphorylation of the Cbl protooncogene. The third aim is to understand better pathways employed by the EGF receptor family further downstream. The potential for activation of the stress-activated MAP kinases will be examined, since some evidence exists for Cdc42 activation, and the identity of a novel GTP-binding protein activated by EGF and heregulin will also be explored. The GTP-binding protein is nuclear, binds RCC1, and is activated by UV light as well as growth factors.

描述（改编自研究者摘要）：本应用程序是 更新RO1以了解EGF受体 家庭成员被激活并发出信号。 受体家族包括 EGF受体Neu、ErbB3和ErbB4。 在报告中指出， 配体与特定受体的结合诱导或 稳定同二聚体或异二聚体的形成。 后者的性质是 特别有趣，但不是特别出名。 初始 该提案的重点是在ErbB3和 EGF受体和EGF受体第一个目标涉及 激活，特别是如何ErbB3，这不是一个有效的酪氨酸 激酶，促进Neu结合调蛋白后的活化，以及Neu是否 EGF受体的作用。 这两个问题的答案将是 通过将纯化的正常或突变蛋白质在 磷脂囊泡。 第二个目标是近端信号传导 分子。 一种假说是Neu对ErbB3的酪氨酸磷酸化作用可能是由于Neu 说明ErbB3与p85的结合。 还需要审查的是机制 EGF受体通过其实现Cbl原癌基因的磷酸化。 第三个目的是了解EGF受体更好的途径 家在下游。 潜在的激活 由于存在一些证据，将对应激激活的MAP激酶进行检查 Cdc42激活，以及一种新的GTP结合蛋白的身份 EGF和Heregulin的作用也将被研究。 gtp结合 蛋白质是核的，结合RCC1，并被UV光激活， 生长因子