G PROTEIN PATHWAY IN DROSOPHILA

异三聚体鸟嘌呤核苷酸结合蛋白(G蛋白) 传递各种信号(如激素、神经递质和 光)通过偶联跨膜受体穿过质膜 细胞内的效应器。G蛋白由三种截然不同的蛋白质组成 亚基：α(定义杂三聚体、β和伽马)。Alpha 根据序列，亚基可分为四类 相似之处。G12类的成员是潜在的癌基因，因为 激活突变体具有很强的转化活性。讯号 由G12类成员介导的转导通路很差 明白了。我提议研究果蝇的G12途径 一种强大的基因系统，非常适合解剖 新的信号通路。果蝇基因concontina编码一个G G12类蛋白α亚基(CTA)，是 在原肠形成过程中协调细胞形状的变化。另一只果蝇 原肠发育所需的基因，即FOG，编码一种分泌蛋白(FOG)。 这可能会激活CTA途径。为了阐明G12 信号通路，我计划研究异位激活的影响 在果蝇CTA途径的基础上，确定该途径的新成分 通过进行显性修饰物筛选和双杂交试验，以及 证明FOG是CTA偶联受体的配体。数不胜数 无脊椎动物和脊椎动物之间信号网络保护的例子 脊椎动物已经被描述，所以鉴定新的成分 果蝇中的G12通路可能与我们的 对人类这一重要途径的理解。

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.