University of Magdeburg, Department of Medical Microbiology, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Eur J Cell Biol. 2011 Nov;90(11):880-90. doi: 10.1016/j.ejcb.2010.11.006. Epub 2011 Jan 17.
The clinical outcome of infections with Helicobacter pylori is determined by a complex interplay of host-pathogen interactions, and persistent infection with this pathogen is the major cause of developing chronic gastritis, peptic ulcers and gastric cancer. Highly virulent strains encode a so-called type IV secretion system which translocates the CagA effector protein into gastric epithelial target cells. Injected CagA becomes tyrosine-phosphorylated on EPIYA sequence motifs by Src and Abl family kinase members. CagA then binds to and activates/inactivates various signalling proteins in a phosphorylation-dependent and phosphorylation-independent manner. In this way injected CagA can act as a master key that evolved during evolution the ability to highjack multiple downstream signalling cascades. Here we review our knowledge on the tyrosine phosphorylation motifs in CagA, the recent advances in the interaction of CagA with Src and Abl tyrosine kinases and their role in signalling events leading to changes of the phosphorylation status of actin-binding proteins cortactin, ezrin and vinculin followed by actin-cytoskeletal rearrangements, cell scattering and elongation. Detailed investigation of these pathways will help to yield novel insights and to elucidate the mechanisms of H. pylori-induced pathogenesis.
幽门螺杆菌感染的临床结果取决于宿主-病原体相互作用的复杂相互作用，而这种病原体的持续感染是导致慢性胃炎、消化性溃疡和胃癌的主要原因。高毒力菌株编码一种所谓的 IV 型分泌系统，该系统将 CagA 效应蛋白易位到胃上皮靶细胞中。注射的 CagA 通过Src 和 Abl 家族激酶成员在 EPIYA 序列基序上酪氨酸磷酸化。然后，CagA 以依赖和非依赖于磷酸化的方式结合并激活/失活各种信号蛋白。通过这种方式，注射的 CagA 可以作为一种万能钥匙，在进化过程中获得了劫持多种下游信号级联的能力。在这里，我们回顾了我们对 CagA 中酪氨酸磷酸化基序的了解，最近 CagA 与 Src 和 Abl 酪氨酸激酶相互作用的进展，以及它们在导致肌动蛋白结合蛋白 cortactin、ezrin 和 vinculin 的磷酸化状态发生变化的信号事件中的作用，随后是肌动蛋白细胞骨架重排、细胞散射和伸长。对这些途径的详细研究将有助于提供新的见解，并阐明幽门螺杆菌诱导发病机制的机制。
