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

Rho GTP酶是Ras表基因家族的小GTP结合蛋白，在GTP酶周期中受到调节。一些细菌毒素通过脱酰胺激活Rho蛋白，例如细胞毒性坏死性因子家族（CNFs）。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CNFs进行了详细的分析。我们知道它们是如何被吸收的，以及每个家族成员激活了哪一组Rho GTPases。此外，我们产生了具有不同底物特异性的毒素嵌合体，现在有一套细胞穿透Rho激活剂，我们将用于分析Rho依赖的信号通路。此外，毒素和毒素变异将有助于了解Rho信号通路彼此之间的影响。毒素的一个基本优势是它们激活Rho gtpase而不过度表达活性突变体，这肯定会破坏Rho gtpase和GDI数量之间的细胞平衡。

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.