Role of a VacA receptor in the Helicobacter pylori infection
| Project/Area Number |
16K08778
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ピロリ菌 / VacA / Helicobacter pylori / CagA / Cage |
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| Outline of Final Research Achievements |
Helicobacter pylori is a major cause of gastroduodenal diseases including gastric cancer and produces virulence factors, VacA and CagA. In this study, we found that VacA induced c-Src phosphorylation in virto infection condition through receptor protein tyrosine phosphatase (RPTP) alpha, a VacA receptor. c-Src is responsible for phosphorylation of CagA in H. pylori infection. We also found that wild-type H. pylori but not a vacA gene-disrupted mutant strain induced phosphorylation of CagA in AZ-521 cells, suggesting that VacA is required for CagA phosphorylation in H. pylori infection. These results indicate that VacA mediates CagA phosphorylation through RPTPα in AZ-521 cells. Therefore, we propose that Src phosphorylation induced by VacA in H. pylori infection is mediated through RPTPα and this event is resulting in activation of c-Src and then leading to CagA phosphorylation.
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| Academic Significance and Societal Importance of the Research Achievements |
医療技術の進歩に関わらず、胃がんは未だに日本における重要な疾患であり続けていることから、有効な対策が求められている。ピロリ菌は日本における胃がん発症において最も重要な要因であることから、本感染症を制御することができれば日本の胃がんや関連する疾患を制御することに繋がる。本研究で得られた成果は、ピロリ菌が産生する主要な2つの病原因子（VacAとCagA）の機能的な相互作用を示すものである。つまり、どちらか一方の病原因子の機能を抑制することができれば本菌の病原性の低減に繋がることを意味するものであり、今後の研究の一層の進展が待たれる。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Helicovanter pylori VacA, acting through receptor tyrosine phosphatase is crucial for CagA phosphorylation in human duodenal carcinoma cell line AZ-521.2016
Author(s)
Nakano, M., Yahiro, K., Yamazaki, E., Kurazono, H., Akada, J.K., Yamaoka, Y., Niidome, T., Hatakeyama, M., Suzuki, H., Yamamoto, T. Moss, J. and Hirayama, T.
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Journal Title
Disease models & mechanisms
Volume: 9
Pages: 1473-1481
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Helicobacter pylori detection by γ-glutamyltranspeptidase- activated Fluorescent probe2017
Author(s)
Akashi T, Matsushima K, Kanda T, Nakano M, Kamiya M, Akazawa Y, Ohtani K, Takeshita F, Nakao K, Ueno Y, Isomoto H
Organizer
UNITED EUROPEAN GASTROENTEROLOGY WEEK Annual Meeting 2017
Related Report
Int'l Joint Research
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