Helicobacter pylori stimulates epithelial cell migration via CagA-mediated perturbation of host cell signaling
Helicobacter pylori stimulates epithelial cell migration via CagA-mediated perturbation of host cell signaling
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DOI：
10.1016/j.micinf.2011.12.003
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Hatakeyama, Masanori
中科院分区：
文献类型：
--
作者：
Kikuchi, Kenji;Murata-Kamiya, Naoko;Hatakeyama, Masanori
幽门螺杆菌 CagA 被递送到胃上皮细胞中，在 Glu-Pro-Ile-Tyr-Ala (EPIYA) 基序上进行酪氨酸磷酸化，与含有 Src 同源性 2 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) 序列与分区缺陷 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学作用，我们生成了产生磷酸化抗性 CagA 和不带 CM 序列的 CagA 的幽门螺杆菌同基因菌株。感染研究表明，上皮细胞运动失调在野生型菌株中比在突变型菌株中更为突出。因此，CagA-SHP2 和 CagA-PAR1 相互作用均参与 cagA 阳性幽门螺杆菌的致病性。 (c) 2011 年巴斯德研究所。由 Elsevier Masson SAS 出版。版权所有。
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. (c) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.