Influence of Rho acitvating bacterial toxins on the regulation of Rho GTPase signaling networks

Rho 激活细菌毒素对 Rho GTPase 信号网络调节的影响

• 批准号: 54002476
• 负责人: Professorin Dr. Gudula Schmidt
• 金额: --
• 依托单位: Abteilung I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/54002476?language=en
• 关键词: Influence; Rho; acitvating; bacterial; toxins

Rho GTPases are small GTP binding proteins of the Ras supergene family, which are regulated in a GTPase cycle. Some bacterial toxins activate Rho proteins by deamidation, for example the family of cytotoxic necrotizing factors (CNFs). It encompasses 4 members: CNF1, CNF2 and CNF3 are produced by pathogenic Escherichia coli strains, CNFY by Yersinia pseudotuberculosis. In recent years, we have analyzed the CNFs in detail. We know how they are taken up and which set of Rho GTPases is activated by each family member. Additionally, we generated toxin chimeras with varying substrate specificity and now have a set of cell penetrating Rho activators, which we will use for analyzing Rho-dependent signaling pathways. Moreover, the toxins and toxin variants will help to understand the influence of the Rho signaling pathways among each other. A fundamental advantage of the toxins is that they activate Rho GTPases without over-expression of active mutants, which definitely destroys the cellular balance between the amount of Rho GTPases and GDI.

Rho GTP酶是Ras超基因家族的小GTP结合蛋白，其在GTP酶循环中受到调节。一些细菌毒素通过脱酰胺作用激活Rho蛋白，例如细胞毒性坏死因子（CNF）家族。它包括4个成员：CNF1、CNF2和CNF3由致病性大肠杆菌菌株产生，CNFY由假结核耶尔森菌产生。近年来，我们对CNF进行了详细的分析。我们知道它们是如何被吸收的，以及每个家庭成员激活哪组Rho GTP酶。此外，我们产生了不同的底物特异性的毒素嵌合体，现在有一套细胞穿透Rho激活剂，我们将使用它来分析Rho依赖的信号通路。此外，毒素和毒素变体将有助于了解Rho信号通路相互之间的影响。毒素的一个基本优点是它们激活Rho GTP酶而不过度表达活性突变体，这肯定会破坏Rho GTP酶和GDI的量之间的细胞平衡。