The identification of novel components of the Drosophila JAK/STAT pathway

果蝇 JAK/STAT 通路新成分的鉴定

• 批准号: 5290970
• 负责人: Dr. Martin Zeidler
• 金额: --
• 依托单位: Department of Biomedical Science
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5290970?language=en
• 关键词: identification; novel; components; Drosophila; JAK

The JAK/STAT signal transduction pathway has been conserved throughout evolution and has been implicated in some leukemias and developmental events including haematopoiesis. As a result considerable work has been undertaken in vitro and in tissue culture systems to characterise the components and functions of the pathway. However no genetically based approach to identifying pathway components has yet been undertaken. I therefore propose to undertake a systematic genetic screen to isolate genes which interact with the JAK/STAT pathway conserved in Drosophila. I have developed a Drosophila stock that over-expresses the fly JAK/STAT pathway ligand in the eye and results in cellular over-proliferation. This proliferation produces a massive overgrowth and enlargement of the adult eye that is both easily visible in a binocular microscope and dependent on signalling by the downstream pathway components. Initial results indicate that the screen is feasible and have defined genomic regions that contain interacting genes. A small scale pre-screen has identified a number of genes that appear to be involved in JAK/STAT signalling. Two of these contain P-element insertions and represent a homologue of a known tumour suppresser and a zinc finger protein. Follow up investigations into the function of genes identified by the screen will be undertaken and their role in JAK/STAT signalling and development will be analysed. In the long term, it is hoped to be able to identify novel components of the JAK/STAT signalling pathway and understand the mechanisms that regulate its activity.

JAK/STAT信号转导通路在整个进化过程中一直是保守的，并与一些白血病和发育事件（包括造血）有关。因此，在体外和组织培养系统中已经进行了大量的工作来验证该途径的组分和功能。然而，尚未采取基于遗传的方法来鉴定途径组分。因此，我建议进行系统的遗传筛选，分离基因与JAK/STAT途径在果蝇中保守的相互作用。我开发了一种果蝇原种，其在眼睛中过表达果蝇JAK/STAT途径配体并导致细胞过度增殖。这种增殖产生了大量的过度生长和成人眼睛的扩大，这在双目显微镜下很容易看到，并依赖于下游通路组件的信号传导。初步结果表明，屏幕是可行的，并已定义的基因组区域，包含相互作用的基因。一个小规模的预筛选已经确定了一些似乎参与JAK/STAT信号传导的基因。其中两个含有P-元件插入，并代表一个已知的肿瘤抑制剂和锌指蛋白的同源物。将对通过筛选鉴定的基因的功能进行后续调查，并分析其在JAK/STAT信号传导和发育中的作用。从长远来看，希望能够识别JAK/STAT信号通路的新组分，并了解调节其活性的机制。