Role of Abl and Src family kinases in actin-cytoskeletal rearrangements induced by the Helicobacter pylori CagA protein.
Role of Abl and Src family kinases in actin-cytoskeletal rearrangements induced by the Helicobacter pylori CagA protein.
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DOI：
10.1016/j.ejcb.2010.11.006
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发表时间：
2011-11
影响因子：
6.6
通讯作者：
Nicole Tegtmeyer;S. Backert
中科院分区：
文献类型：
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作者：
Nicole Tegtmeyer;S. Backert
幽门螺杆菌感染的临床结果是由宿主-病原体相互作用的复杂相互作用决定的，并且该病原体的持续感染是发展为慢性胃炎、消化性溃疡和胃癌的主要原因。高毒力菌株编码所谓的IV型分泌系统，其将CagA效应蛋白易位到胃上皮靶细胞中。注射的CagA在EPIYA序列基序上被Src和Abl家族激酶成员酪氨酸磷酸化。然后，CagA以磷酸化依赖性和磷酸化非依赖性方式结合并激活/灭活各种信号传导蛋白。以这种方式，注入的CagA可以充当主密钥，其在进化过程中进化出劫持多个下游信号级联的能力。在这里，我们回顾我们的知识在CagA中的酪氨酸磷酸化基序，最近的进展CagA与Src和Abl酪氨酸激酶的相互作用及其在信号事件中的作用，导致肌动蛋白结合蛋白corpine，ezrin和黏着斑蛋白的磷酸化状态的变化，随后肌动蛋白细胞骨架重排，细胞散射和伸长。对这些通路的详细研究将有助于产生新的见解，并阐明H。幽门螺杆菌致病
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.