Notch信号是动物发育过程中一个非常重要且高度保守的信号通路，影响细胞增殖、凋亡、命运决定等众多生命活动。目前研究表明多种蛋白激酶通过磷酸化该通路成员蛋白而调节其活性，但是针对去磷酸化过程的关键执行者，磷酸酶在该通路中的功能和机制迄今所知甚少。申请人在前期研究中发现了两个调控Notch信号的磷酸酶基因：mts和ppv。本项目拟在此基础上，以果蝇及培养细胞系为材料，利用发育生物学和细胞生物学等手段，对mts和ppv调控Notch信号活性和胚胎发育方面的功能进行深入系统的研究，其次通过解析这两个磷酸酶的复合体组成、作用靶蛋白、磷酸酶与靶蛋白间的互作模式等，阐明其调控Notch信号通路的分子机制，最后验证该磷酸酶基因功能和机制的保守性。本项目旨在探究以磷酸酶为核心的蛋白质去磷酸化修饰对于Notch信号的动态调控机制，预期成果将为深入理解Notch信号的调控机理提供重要的理论依据。

Notch signaling is a very important and highly conserved signal transduction pathway, being repeatedly employed in the tissue and organ development. Improper signaling activity results in many birth defects and diseases. Therefore, this signaling must be accurately regulated. Notch signaling can be regulated by protein phosphorylation, which is one of the most common protein post-translational modifications and is controlled by protein kinase and phosphatase. Despite the protein kinases caught most attentions in past, recently, more and more studies are revealing that protein phosphatases plays specific and important roles in many cellular events. But to date, the role of protein phosphatases in Notch pathway remains elusive. Based on the preliminary work, two protein phosphatase genes, mts and ppv, were newly identified to be involved in Notch pathway. This project will first take advantages of Drosophila model to study the function of protein phosphatases in regulating Notch signaling, and the underlying molecular mechanisms by characterizing the specific substrate of Mts or PPV in Notch pathway. Moreover, the zebrafish model will be used to further reveal whether the role of phosphatases is conserved in vertebrates. This study is aiming to search for the new regulator of Notch signaling, clarify the functional conservation of the regulators among different species. The prospective result will definitely improve the understanding of the regulatory mechanisms for Notch pathway, provide new insight for the role of protein phosphatases in regulating signal transduction and animal development.