EXPRESSION AND STRUCTURE OF INVERTEBRATE ONCOGENES

果蝇EGF受体基因突变影响一系列重要的 和发展过程。这项研究计划的长期目标是 目的是确定生长因子受体酪氨酸激酶在 通过详细的遗传学和分子遗传学研究， 这个模型系统。希望这些研究的结果能够 扩展到脊椎动物系统，从而阐明了 细胞和转化生长因子受体酪氨酸激酶 正常发育和肿瘤性疾病。的具体目标 目前的建议是：（1）。为了完成对 抑制椭圆（Elp）类EGF的基因外突变 受体突变Elp等位基因表现为显性粗眼表型。 P元件突变诱导的5个抑癌基因突变， 已被隔离，并将进行分析，就相互作用， EGF受体基因的突变与相互作用（二）、到 在分子水平上分析一组ELP抑制子。上 根据基因测试，某些ELP抑制基因突变将 进行分子克隆和测序，以了解 EGF受体信号通路（三）、以确定基因 作为隐性DER基因突变的基因外抑制因子， 眼睛以外的其他组织。这类突变将代表 DER信号通路元件中的功能获得性突变， 可能在眼睛里不起作用。这些结果将揭示是否相同， 不同的，或部分重叠的一组元素在EGF中的功能 不同组织中的受体信号通路。（四）、分离新的 在确定的遗传背景中的Elp类的等位基因，以定义 可以激活显性突变表型的一种或多种机制 EGF受体将进行基因测试，以评估 Elp表型的变异性的可能性。同伴研究在 分子水平将定义蛋白质的结构变化 伴随着表型变异。

Mutations in the Drosophila EGF receptor gene affect a range of vital and developmental processes. The long-term goal of this research program is to define the role(s) of growth factor receptor tyrosine kinases in development through detailed genetic and molecular genetic studies in this model system. It is hoped that the results of these studies can be extended to vertebrate systems and thus shed light on the roles of cellular and transforming growth factor receptor tyrosine kinases in normal development and in neoplastic disease. The Specific Aims of the current proposal are: (1). To complete the genetic characterization of extragenic mutations that suppress the Ellipse (Elp) class of EGF receptor mutations. Elp alleles manifest a dominant rough eye phenotype. Five suppressor gene mutations induced by P element mutagenesis have been isolated and will be analyzed with respect to interaction with recessive EGF receptor gene mutations and with each other. (2). To analyze a subset of the Elp suppressors at the molecular level. On the basis of the genetic tests, certain of the Elp suppressor mutations will be molecularly cloned and sequenced to learn the structure/identity of elements of the EGF receptor signaling pathway. (3). To identify genes acting as extragenic suppressors of recessive DER gene mutations in tissues other than the eye. Mutations of this class would represent gain-of-function mutations in elements of the DER signaling pathway that may not function in the eye. These results will reveal whether the same, different, or partially overlapping set of elements functions in the EGF receptor signaling pathway in different tissues. (4). To isolate new alleles of the Elp class in a defined genetic background to define the mechanism or mechanisms that can activate the dominant mutant phenotype in EGF receptor. Genetic tests will be carried out to assess the potential for variability in the Elp phenotype. Companion studies at the molecular level will define the structural changes in the protein accompanying phenotypic variation.