Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism
Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism
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DOI：
10.1046/j.1462-5822.2003.00236.x
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发表时间：
2003-01-01
影响因子：
3.4
通讯作者：
Fällman, M
中科院分区：
文献类型：
--
作者：
Deleuil, F;Mogemark, L;Fällman, M
酪氨酸磷酸酶YopH是致病性耶尔森菌产生的重要毒力因子。YopH通过III型分泌系统转运到宿主细胞中，其去磷酸化活性导致局灶复杂结构的破坏和吞噬过程的阻断。YopH的宿主细胞靶点包括上皮细胞中的局灶黏附蛋白crk相关底物（p130(Cas)）和局灶黏附激酶（FAK），以及巨噬细胞中的p130（Cas）和fyn结合蛋白（Fyb）。先前的研究表明，YopH的n端结构域是一个底物结合结构域。本研究阐明了YopH靶向病灶复合物的机制及其与p130(Cas)/Fyb相互作用的生物学意义。构建了p130(Cas)/Fyb结合缺陷但与野生型难以区分的YopH突变体。无法结合p130（Cas）的突变体无法定位到感染细胞中的局灶复杂结构，这表明与p130（Cas）的关联对于YopH的适当亚细胞定位至关重要。这些yopH突变体的毒力也明显减弱，表明与p130（Cas）和/或Fyb的结合在耶尔森菌感染中具有生物学相关性。
The tyrosine phosphatase YopH is an essential virulence factor produced by pathogenic Yersinia species. YopH is translocated into host cells via a type III secretion system and its dephosphorylating activity causes disruption of focal complex structures and blockage of the phagocytic process. Among the host cell targets of YopH are the focal adhesion proteins Crk-associated substrate (p130(Cas)) and focal adhesion kinase (FAK) in epithelial cells, and p130(Cas) and Fyn-binding protein (Fyb) in macrophages. Previous studies have shown that the N-terminal domain of YopH acts as a substrate-binding domain. In this study, the mechanism and biological importance of the targeting of YopH to focal complexes relative to its interaction with p130(Cas)/Fyb was elucidated. Mutants of YopH that were defective in p130(Cas)/Fyb binding but otherwise indistinguishable from wild type were constructed. Mutants unable to bind p130(Cas) did not localize to focal complex structures in infected cells, indicating that the association with p130(Cas) is critical for appropriate subcellular localization of YopH. These yopH mutants were also clearly attenuated in virulence, showing that binding to p130(Cas) and/or Fyb is biologically relevant in Yersinia infections.