G PROTEIN PATHWAY IN DROSOPHILA

异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白） 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 与细胞内效应器。 G蛋白由三种不同的 亚基：α（其定义异源三聚体、β和γ）。 阿尔法 亚单位可根据序列分为四类 相似之处 G12类的成员是潜在的致癌基因， 活化突变体具有高度有效的转化活性。 信号 由G12类成员介导的转导途径很差， 明白 我打算研究果蝇的G12通路 黑腹，一个强大的遗传系统，是理想的解剖， 新的信号通路。 果蝇的手风琴基因编码一个G G12类蛋白α亚基（CTA）， 原肠胚形成过程中协调的细胞形状变化。 另一只果蝇 原肠胚形成过程中所需的基因fog编码一种分泌蛋白（FOG） 有可能激活CTA通路 为了阐明G12 信号通路，我计划检查异位激活的影响， 在果蝇CTA通路中，识别通路的新组分 通过进行显性修饰物筛选和双杂交测定， 证明FOG是CTA偶联受体的配体。 许多 无脊椎动物之间的信号网络的保护的例子， 已经描述了脊椎动物，所以鉴定新的成分， 果蝇中G12通路可能与我们的 了解人类的这一重要途径。

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.