Do Jin Kim^a, Kang-Seo Park^b, Jung-Ho Kim^c, Sang-Hwa Yang^c, Ji Young Yoon^a, Byeong-Gu Han^d, Hyoun Sook Kim^a, Sang Jae Lee^a, Jun Young Jang^a, Kyoung Hoon Kim^a, Mi Jung Kim^a, Jin-Su Song^a, Hie-Joon Kim^a, Chung-Mo Park^a, Sang-Kyou Lee^c,1, Byung Il Lee^d,1, and Se Won Suh^a,e,1

^aDepartment of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea;
^bDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Korea;
^cDepartment of Biotechnology, College of Life Science and Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Korea;
^dCancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Korea; and
^eDepartment of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea

Edited* by Sung-Hou Kim, University of California, Berkeley, CA, and approved October 20, 2010 (received for review July 15, 2010)

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).

Footnotes

¹To whom correspondence may be addressed.

Author contributions: D.J.K., K.-S.P., S.-K.L., B.I.L., and S.W.S. designed research; D.J.K., K.-S.P., J.-H.K., S.-H.Y., J.Y.Y., B.-G.H., M.J.K., and J.-S.S. performed research; H.-J.K., C.-M.P., S.-K.L., B.I.L., and S.W.S. contributed new reagents/analytic tools; D.J.K., K.-S.P., J.-H.K., S.-H.Y., H.S.K., S.J.L., J.Y.J., K.H.K., M.J.K., J.-S.S., H.-J.K., C.-M.P., S.-K.L., B.I.L., and S.W.S. analyzed data; and D.J.K., S.-K.L., B.I.L., and S.W.S. wrote the paper.

The authors declare no conflict of interest.

*This Direct Submission article had a prearranged editor.

Data deposition: Atomic coordinates of the refined structures have been deposited in the Protein Data Bank, http://www.pdb.org [PDB ID codes 3AKJ (Apo), 3AKK (ADP-complex), and 3AKL (AMP-PNP-complex)].

This article contains supporting information online at
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1010153107/-/DCSupplemental.