权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Annexin A2 and the regulation of actin cytoskeletal dynamics

膜联蛋白 A2 和肌动蛋白细胞骨架动力学的调节

基本信息

批准号：
127795095
负责人：
Professorin Dr. Ursula Rescher
金额：
--
依托单位：
Institut für Medizinische Biochemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/127795095?language=en
关键词：
Annexin A2 regulation actin cytoskeletal

项目摘要

PI(4,5)P2 enriched membrane microdomains are essentially involved in cell signalling, membrane trafficking, cell motility and polarity. Upon extracellular stimulation, these domains, often called rafts, cluster to form signalling platforms that recruit and accumulate signalling components including those regulating the actin cytoskeleton, thus providing an environment which links cellular signalling and the regulation of actin dynamics. Annexin A2, a substrate of the src-tyrosine kinase and several receptor tyrosine kinases, is one of the best characterized raft-associated proteins. It has recently emerged as a PI(4,5)P2 binding protein and induces the lateral segregation of membrane lipids, suggesting a role in the formation and stabilization of larger raft aggregates. Current evidence indicates a causal role for annexin A2 in the dynamic assembly of actin at rafts, which affects adhesion and motility. We propose that annexin A2 tyrosine phosphorylation functions as a molecular switch that modulates actin-based cellular motility, leading to a more motile phenotype. We want to elucidate the annexin A2 action at a mechanistic level. Firstly, we will characterize the temporal and spatial control of annexin A2 tyrosine phosphorylation. Secondly, we will explore which pathways are targeted by tyrosine phosphorylated annexin A2. Thirdly, we will investigate whether tyrosine phosphorylation of annexin A2 plays a role in tumour biology.We will address these key questions both in vitro and in vivo by biochemical and cell-based approaches, complemented by live cell imaging techniques.

PI（4，5）P2富集的膜微区基本上参与细胞信号传导、膜运输、细胞运动性和极性。在细胞外刺激时，这些结构域，通常称为筏，聚集形成信号平台，募集和积累信号组分，包括那些调节肌动蛋白细胞骨架，从而提供了一个连接细胞信号和肌动蛋白动力学调节的环境。膜联蛋白A2是src-酪氨酸激酶和几种受体酪氨酸激酶的底物，是最具特征的筏相关蛋白之一。它最近出现作为PI（4，5）P2结合蛋白，并诱导膜脂的横向分离，这表明在较大的筏聚集体的形成和稳定的作用。目前的证据表明，膜联蛋白A2的因果关系的作用，肌动蛋白在筏，影响粘附和运动的动态组装。我们提出，膜联蛋白A2酪氨酸磷酸化作为一个分子开关，调节肌动蛋白为基础的细胞运动，导致更多的运动表型。我们想阐明膜联蛋白A2的作用机制。首先，我们将描述膜联蛋白A2酪氨酸磷酸化的时间和空间控制。其次，我们将探索哪些途径是酪氨酸磷酸化的膜联蛋白A2的靶向。第三，我们将研究膜联蛋白A2的酪氨酸磷酸化是否在肿瘤生物学中起作用，我们将通过生物化学和细胞为基础的方法，辅以活细胞成像技术，在体外和体内解决这些关键问题。