Inhibition of MAPK signaling pathways by VopA from Vibrio parahaemolyticus
Inhibition of MAPK signaling pathways by VopA from Vibrio parahaemolyticus
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DOI：
10.1074/jbc.m407001200
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发表时间：
2004-12-10
影响因子：
4.8
通讯作者：
Orth, K
中科院分区：
文献类型：
--
作者：
Trosky, JE;Mukherjee, S;Orth, K
在感染期间，细菌病原体利用III型分泌系统将效应物注射到靶细胞的细胞质中，在那里它们破坏宿主细胞的防御系统。副溶血性弧菌（Vibrio parahaemolyticus）是东南亚流行性胃肠炎的病原体，具有III型分泌系统，其编码YopJ样蛋白效应子家族的新成员VopA（Vibrio outer protein A）。我们的研究表明，Vibrio VopA编码一种进化上保守的活性，这种活性非常有效，需要一个完整的催化位点以不同于其他YopJ样效应物的方式废除信号通路。我们观察到，VopA有效地抑制MAPK信号通路，但不抑制哺乳动物细胞中的NF κ B通路。当在酵母中表达时，VopA诱导生长停滞表型并且还阻断酵母MAPK信号传导途径。我们的观察提供了深入了解YopJ样效应物利用的靶点的巨大多样性，以操纵真核细胞信号传导机制，这些机制对于感染和/或共生期间宿主细胞的响应和存活是重要的。
During infection, bacterial pathogens utilize a type III secretion system to inject effectors into the cytoplasm of a target cell where they disrupt the defense system of the host cell. Vibrio parahaemolyticus, a causative agent of gastroenteritis endemic in Southeast Asia, has a type III secretion system that encodes a novel member of the YopJ-like protein effector family, VopA ( Vibrio outer protein A). Our studies revealed that Vibrio VopA encodes an evolutionarily conserved activity that is extremely potent and requires an intact catalytic site to abrogate signaling pathways in a manner distinct from that of other YopJ-like effectors. We observed that VopA efficiently inhibits the MAPK signaling pathways but not the NFkappaB pathway in mammalian cells. When expressed in yeast, VopA induces a growth arrest phenotype and also blocks yeast MAPK signaling pathways. Our observations provide insight into the immense diversity of targets utilized by YopJ-like effectors to manipulate eukaryotic signaling machineries that are important for the response and survival of the host cell during infection and/or symbiosis.