A Novel Connection between the Yeast Cdc42 GTPase and the Slt2-mediated Cell Integrity Pathway Identified through the Effect of Secreted Salmonella GTPase Modulators*

A Novel Connection between the Yeast Cdc42 GTPase and the Slt2-mediated Cell Integrity Pathway Identified through the Effect of Secreted Salmonella GTPase Modulators*
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通过分泌型沙门氏菌 GTP 酶调节剂的作用鉴定出酵母 Cdc42 GTP 酶与 Slt2 介导的细胞完整性途径之间的新联系*

DOI:
10.1074/jbc.m201527200
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发表时间:
2002
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
M. Molina
M. Molina
中科院分区:
--
文献类型:
--
作者:
José M. Rodrı́guez;H. Martín;G. North;R. Rotger;C. Nombela;M. Molina

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通过注射效应蛋白SopE 2和SptP调节宿主细胞的GTP酶是鼠伤寒沙门氏菌进入非吞噬细胞所必需的。在这里,我们表明,鸟嘌呤核苷酸交换因子Cdc42 SopE2在酿酒酵母中的表达导致Fus3和Kss1 MAPK的激活,这在交配和诱导途径中起作用,导致单倍体酵母细胞中的丝状生长。此外,它促进细胞完整性MAPK Slt2的激活。Cdc42通过去除其假定的内在GTP酶激活蛋白(GAP)Rga 1、Rga 2和Bem 3而活化,也导致Kss 1、Fus3和Slt2 MAPK的磷酸化。这些数据支持这些GAP蛋白作为Cdc42的负调节因子的作用,证实了这种GTdR对表达和交配途径的调节作用,并指出Cdc42和细胞完整性途径之间的新联系。Cdc42诱导的Slt2激活以交配和诱导途径依赖的方式发生,但它不需要Rho 1的功能,Rho 1是在细胞完整性途径中起作用的GT3。此外,我们报告,沙门氏菌SptP可以作为一个缺口的Cdc42在S。酿酒酵母,下调MAPK介导的信号传导。因此,酵母为研究细菌致病蛋白与真核生物信号通路的相互作用提供了一个有用的系统。此外,这些蛋白质可以作为一种工具,以获得深入了解的机制,调节MAPK介导的信号在真核生物。
Modulation of host cellular GTPases through the injection of the effector proteins SopE2 and SptP is essential forSalmonella typhimurium to enter into non-phagocytic cells. Here we show that expression of the guanine nucleotide exchange factor for Cdc42 SopE2 in Saccharomyces cerevisiae leads to the activation of Fus3 and Kss1 MAPKs, which operate in the mating and filamentation pathways, causing filamentous growth in haploid yeast cells. Furthermore, it promotes the activation of the cell integrity MAPK Slt2. Cdc42 activation by removal of its putative intrinsic GTPase-activating proteins (GAPs), Rga1, Rga2, and Bem3, also results in the phosphorylation of Kss1, Fus3, and Slt2 MAPKs. These data support the role of these GAP proteins as negative regulators of Cdc42, confirm the modulating effect of this GTPase on the filamentation and mating pathways and point to a novel connection between Cdc42 and the cell integrity pathway. Cdc42-induced activation of Slt2 occurs in a mating and filamentation pathway-dependent manner, but it does not require the function of Rho1, which is the GTPase that operates in the cell integrity pathway. Moreover, we report that Salmonella SptP can act as a GAP for Cdc42 in S. cerevisiae, down-regulating MAPK-mediated signaling. Thus, yeast provides a useful system to study the interaction of bacterial pathogenic proteins with eukaryotic signaling pathways. Furthermore, these proteins can be used as a tool to gain insight into the mechanisms that regulate MAPK-mediated signaling in eukaryotes.
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