G PROTEIN PATHWAY IN DROSOPHILA

果蝇中的 G 蛋白途径

• 批准号: 6018411
• 负责人: LAURA ANNE LEE
• 金额: $ 1.49万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6018411
• 关键词: Drosophilidae; G protein; biological signal transduction; gene expression; gene mutation; molecular genetics; yeast two hybrid system

Heterotrimeric guanine nucleotide binding proteins (G proteins) transduce a variety of signals (e.g. hormones, neurotransmitters, and light) across the plasma membrane by coupling transmembrane receptors with intracellular effectors. G proteins are composed of three distinct subunits: alpha (which defines the heterotrimer, beta, and gamma. Alpha subunits can be divided into four classes based on sequence similarities. Members of the G12 class are potential oncogenes because activating mutants have highly potent transforming activities. Signal transduction pathways mediated by members of the G12 class are poorly understood. I propose to study the G12 pathway in Drosophila melanogaster, a powerful genetic system that is ideal for dissection of novel signaling pathways. The Drosophila gene concertina encodes a G protein alpha subunit of the G12 class (CTA) that is required for coordinated cell shape changes during gastrulation. Another Drosophila gene required during gastrulation, fog, encodes a secreted protein (FOG) that potentially activates the CTA pathway. To elucidate the G12 signaling pathway, I plan to examine the effects of ectopic activation of the CTA pathway in Drosophila, identify new components of the pathway by performing a dominant modifier screen and a two-hybrid assay, and demonstrate that FOG is a ligand for a CTA-coupled receptor. Numerous examples of conservation of signaling networks between invertebrates and vertebrates have been described, so identification of new components of the G12 pathway in Drosophila will likely have relevance for our understanding of this important pathway in humans.

异三聚鸟嘌呤核苷酸结合蛋白（G 蛋白） 转导多种信号（例如激素、神经递质和 光）通过耦合跨膜受体穿过质膜 与细胞内效应器。 G蛋白由三种不同的 亚基：α（定义异源三聚体、β 和 γ。Alpha 亚基根据序列可分为四类 相似之处。 G12 类成员是潜在的癌基因，因为 激活突变体具有高效的转化活性。 信号 G12类成员介导的转导途径很差 明白了。 我建议研究果蝇的 G12 通路 黑腹果蝇，一个强大的遗传系统，非常适合解剖 新颖的信号通路。 果蝇的手风琴基因编码一个G G12 类 (CTA) 的蛋白质 α 亚基是 原肠胚形成过程中细胞形状的协调变化。 另一种果蝇 原肠胚形成过程中所需的基因，雾，编码分泌蛋白（FOG） 可能会激活 CTA 途径。 阐明G12 信号通路，我计划检查异位激活的影响 果蝇中 CTA 途径的研究，确定该途径的新成分 通过进行显性修饰筛选和双杂交测定，以及 证明 FOG 是 CTA 偶联受体的配体。 很多的 无脊椎动物和动物之间信号网络保护的例子 脊椎动物已经被描述，因此鉴定出脊椎动物的新成分 果蝇中的 G12 通路可能与我们的研究相关 了解人类这一重要途径。