Phosphorylation-independent effects of CagA during interaction between Helicobacter pylori and T84 polarized monolayers
Phosphorylation-independent effects of CagA during interaction between Helicobacter pylori and T84 polarized monolayers
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DOI：
10.1086/424526
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发表时间：
2004-10-15
影响因子：
6.4
通讯作者：
Merrell, DS
中科院分区：
文献类型：
--
作者：
El-Etr, SH;Mueller, A;Merrell, DS
为了扩展我们对幽门螺杆菌宿主细胞靶标的了解，我们表征了幽门螺杆菌和人 T84 上皮细胞极化单层之间的相互作用。使用人类微阵列和一组同基因幽门螺杆菌突变体进行的转录分析揭示了对感染的不同反应。在表达发生变化的 670 个基因中，大多数（92%）需要 cag 致病性岛（PAI）。尽管许多基因表达的改变依赖于 CagA（80% 的 PAI 依赖性基因），但这些宿主基因中超过 30% 的表达与 CagA 蛋白的磷酸化状态无关。同样，我们发现注射的 CagA 定位于细胞的顶端表面，并以不依赖磷酸化的方式优先在顶端连接处积累。这些数据表明 CagA 蛋白内存在不同的功能域，这些功能域在蛋白质靶向和宿主细胞信号传导途径的改变中发挥重要作用。
To extend our knowledge of host-cell targets of Helicobacter pylori, we characterized the interaction between H. pylori and human T84 epithelial cell polarized monolayers. Transcriptional analysis by use of human microarrays and a panel of isogenic H. pylori mutants revealed distinct responses to infection. Of the 670 genes whose expression changed, most (92%) required the cag pathogenicity island (PAI). Although altered expression of many genes was dependent on CagA (80% of the PAI-dependent genes), expression of >30% of these host genes occurred independent of the phosphorylation state of the CagA protein. Similarly, we found that injected CagA localized to the apical surface of cells and showed preferential accumulation at the apical junctions in a phosphorylation-independent manner. These data suggest the presence of distinct functional domains within the CagA protein that play essential roles in protein targeting and alteration of host-cell signaling pathways.