Analysis of Epidermal Growth Factor Receptor Signaling in Drosophila

果蝇表皮生长因子受体信号转导分析

• 批准号: 0090693
• 负责人: Amanda Simcox
• 金额: $ 39万
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0090693&HistoricalAwards=false
• 关键词: Analysis; Epidermal; Growth; Factor; Receptor

0090693SimcoxThe Drosophila EGF receptor (EGFR) is required for a number of developmental processes involving distinct cell responses. Receptor activity is governed by four agonists including Spitz and Vein. The ligands may be deployed for particular developmental events because they induce a certain strength or duration of signaling and hence elicit the desired cell response. Individual and comparative analysis of the ligands will be required to develop this idea. The focus of this proposal is analysis of the neuregulin-like ligand, Vein, and a comparison of Vein with the TGF-a-like ligand, Spitz. There are 3 specific aims: 1) Genetic and biochemical approaches will be used to identify factors that control the biological activity of Vein. 2) The transcriptional control of vein will be investigated by determining if the gene is a direct target of four signaling pathways with which it is known to interact. 3) Differences between Vein and Spitz will be analyzed by comparing the profiles of target-gene induction using DNA microarrays and testing the developmental consequence of substituting the spitz EGF motif for that of vein using homologous recombination. Together, the experiments address a fundamental issue in development concerning how different cell responses are elicited through a single signaling pathway. EGFR (ErbB) tyrosine kinases and their ligands are highly conserved and play important developmental roles in many organisms. Thus, the results found here will have implications beyond Drosophila.

0090693SIMCOX果蝇EGF受体（EGFR）是许多涉及不同细胞反应的发育过程所必需的。 受体活性由包括Spitz和静脉在内的四个激动剂支配。 这些配体可以用于特定的发育事件，因为它们会诱导一定的强度或信号的持续时间，从而引起所需的细胞反应。 需要对配体的个人和比较分析来发展这一想法。 该建议的重点是分析神经蛋白样的配体，静脉，以及静脉与TGF-A样配体Spitz的比较。 有3个具体目的：1）将使用遗传和生化方法来识别控制静脉生物学活性的因素。 2）将通过确定该基因是否是已知相互作用的四个信号通路的直接目标来研究静脉的转录控制。 3）将通过使用DNA微阵列比较靶基因诱导的曲线并测试使用同源重组代替静脉的靶向后果来分析静脉和Spitz之间的差异。 共同解决了有关如何通过单个信号通路引起不同细胞反应的开发中的一个基本问题。 EGFR（ERBB）酪氨酸激酶及其配体是高度保守的，并且在许多生物体中起着重要的发育作用。 因此，此处发现的结果将具有果蝇以外的含义。