Division of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Microbes Infect. 2012 May;14(5):470-6. doi: 10.1016/j.micinf.2011.12.003. Epub 2011 Dec 11.
Helicobacter pylori CagA is delivered into gastric epithelial cells, where undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif to interact with Src homology 2-containing protein tyrosine phosphatase-2 (SHP2) oncoprotein. CagA also binds to partitioning-defective 1 (PAR1) polarity-regulating kinase via the CagA multimerization (CM) sequence. To investigate pathophysiological role of CagA-SHP2 and/or CagA-PAR1 interaction in H. pylori infection, we generated H. pylori isogenic strains producing a phosphorylation-resistant CagA and a CagA without CM sequence. Infection studies revealed that deregulation of epithelial cell motility was more prominent in the wild-type strain than in the mutant strains. Thus, both CagA-SHP2 and CagA-PAR1 interactions are involved in the pathogenicity of cagA-positive H. pylori.
幽门螺杆菌 CagA 被递送至胃上皮细胞，在那里 CagA 在 Glu-Pro-Ile-Tyr-Ala（EPIYA）基序处经历酪氨酸磷酸化，以与Src 同源 2 结构域含有的蛋白酪氨酸磷酸酶-2（SHP2）癌蛋白相互作用。CagA 还通过 CagA 多聚化（CM）序列与分隔缺陷 1（PAR1）极性调节激酶结合。为了研究 CagA-SHP2 和/或 CagA-PAR1 相互作用在幽门螺杆菌感染中的病理生理作用，我们生成了产生磷酸化抗性 CagA 和没有 CM 序列的 CagA 的幽门螺杆菌同基因株。感染研究表明，上皮细胞运动的失调在野生型菌株中比在突变菌株中更为明显。因此，CagA-SHP2 和 CagA-PAR1 相互作用均参与了 cagA 阳性幽门螺杆菌的致病性。
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