Genetic Analysis of JAK Signaling in Drosophila

不同细胞类型的协调增殖和分化对任何多细胞生物的正常发育和维持至关重要。为了实现这种协调，细胞之间必须有一种相互沟通的方式。这项研究的长期目标是阐明细胞-细胞信号传导的机制，并了解不同的信号是如何被解释以调节发育事件的。为此，我们将对黑腹果蝇的Janus激酶（JAK）信号通路进行研究。这个系统之所以会被使用，是因为它在发育上很重要，相对简单，并且在苍蝇和哺乳动物之间是保守的。在哺乳动物中，已知该途径由非受体酪氨酸激酶（JAKs）和信号转导和转录激活因子（STATs）组成。在果蝇中，最近发现了一个JAK（跳房子）和一个STAT（马瑞尔）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信号的一个新成分，unpaired （upd）。了解upd参与JAK信号传导是本研究的核心。JAK途径的其他分子，或与该途径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。本研究的具体目标是：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)确定与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