Genetic Analysis of JAK Signaling in Drosophila

哈里森9723944 不同细胞类型的协调增殖和分化对于任何多细胞生物体的正常发育和维持至关重要。 为了实现这种协调，细胞必须有一种相互通信的手段。 这项研究的广泛的长期目标是阐明细胞间信号传导的机制，并了解不同的信号是如何被解释为调节发育事件的。 为了实现这些目标，Janus激酶（JAK）信号通路将在果蝇中进行研究。 这个系统将被使用，因为它是发展重要的，相对简单，是苍蝇和哺乳动物之间的保守。 在哺乳动物中，已知该途径由非受体酪氨酸激酶（JAK）和信号转导和转录激活因子（STAT）组成。 在果蝇中，最近已经鉴定出一个JAK（跳房子）和一个STAT（marelle）基因。 果蝇的遗传和发育操作使其成为进一步研究JAK/STAT信号的理想模型系统。 这些方法将补充和扩展在哺乳动物细胞中进行的途径的生化分析。 突变分析已经发现了果蝇JAK/STAT信号的一个新组成部分，未配对（upd）。 了解upd参与JAK信号转导是这里提出的研究的核心。 JAK通路的其他分子，或与该通路的组分强烈相互作用的分子，将使用果蝇中可用的遗传工具进行鉴定和表征。 这项研究的具体目标是： 1)在分子水平上表征未配对位点2）确定Upd产物在JAK信号传导中的功能3）表征Upd功能在果蝇发育中的作用4）鉴定与JAK通路相互作用的其他组分和因子

Harrison 9723944 The coordinated proliferation and differentiation of distinct cell types is critical to the proper development and maintenance of any multicellular organism. For this coordination to occur, cells must have a means to communicate with one another. The broad long-term objectives of this research are to elucidate mechanisms of cell-cell signaling and to understand how different signals are interpreted to regulate developmental events. Toward these goals, the Janus kinase (JAK) signaling pathway will be studied in Drosophila melanogaster. This system will be used because it is developmentally important, relatively simple, and is conserved between flies and mammals. In mammals, the pathway is know to be comprised of the non-receptor tyrosine kinases (JAKs) and the signal transducers and activators of transcription (STATs). In flies, one JAK (hopscotch) and one STAT (marelle) gene have been recently identified. The genetic and developmental manipulations available in Drosophila make it an ideal model system to further study JAK/STAT signaling. These approaches will complement and extend the biochemical analyses of the pathway conducted in mammalian cells. Mutational analysis has already uncovered a new component of JAK/STAT signaling in Drosophila, unpaired (upd). An understanding of the involvement of upd in JAK signaling is central to the research proposed here. Other molecules integral to the JAK pathway, or that strongly interact with components of the pathway, will be identified and characterized using the genetic tools available in Drosophila. The specific goals of this research are to: 1) Characterize the unpaired locus at the molecular level 2) Determine the functions of the Upd product in JAK signaling 3) Characterize the roles of Upd function in Drosophila development 4) Identify other components of and factors interacting with the JAK pathway