Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase

Do Jin Kim, Kang Seo Park, Jung Ho Kim, Sang Hwa Yang, Ji Young Yoon, Byeong Gu Han, Hyoun Sook Kim, Sang Jae Lee, Jun Young Jang, Kyoung Hoon Kim, Mi Jung Kim, Jin Su Song, Hie Joon Kim, Chung Mo Park, Sang Kyou Lee, Byung Il Lee, Se Won Suh

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Abstract

There has been considerable interest in virulence genes in the plasticity region of Helicobacter pylori, but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of H. pylori strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-κB in cultured macrophages. Here we have characterized the structure and function of JHP940 to provide the framework for better understanding its role in inflammation by H. pylori. Our work demonstrates that JHP940 is the first example of a eukaryotic-type Ser/Thr kinase from H. pylori. We show that JHP940 is catalytically active as a protein kinase and translocates into cultured human cells. Furthermore, the kinase activity is indispensable for indirectly up-regulating phosphorylation of NF-κB p65 at Ser276. Our results, taken together, contribute significantly to understanding the molecular basis of the role of JHP940 in inflammation and subsequent pathogenesis caused by H. pylori.We propose to rename the jhp940 gene as ctkA (cell translocating kinase A).

Original languageEnglish
Pages (from-to)21418-21423
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
Publication statusPublished - 2010 Dec 14

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Kim, D. J., Park, K. S., Kim, J. H., Yang, S. H., Yoon, J. Y., Han, B. G., Kim, H. S., Lee, S. J., Jang, J. Y., Kim, K. H., Kim, M. J., Song, J. S., Kim, H. J., Park, C. M., Lee, S. K., Il Lee, B., & Suh, S. W. (2010). Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase. Proceedings of the National Academy of Sciences of the United States of America, 107(50), 21418-21423. https://doi.org/10.1073/pnas.1010153107