Analysis of the phosphatase that is a novel binding target for the Helicobacter pylori virulence factor CagA in the host cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: FUJII Yumiko 旭川医科大学, 医学部, 助教 (30722334)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヘリコバクター・ピロリ / CagA / 脂質ホスファターゼ

Outline of Final Research Achievements

The SH2 domain-containing inositol phosphatase SHIP2 was identified as a novel binding target for tyrosine-phosphorylated CagA in gastric epithelial cells. It was shown that CagA recruits SHIP2 to the plasma membrane of the host cells and enhances the phospholipid phosphatase activity of SHIP2 to change the phosphatidylinositol composition of the plasma membrane to which H. pylori adheres. Furthermore, it was revealed that SHIP2 increases the delivery of CagA from H. pylori into the host cells.

Free Research Field

分子腫瘍学、感染腫瘍学

Academic Significance and Societal Importance of the Research Achievements

SHIP2はCagAと結合することで胃上皮細胞内へのCagAの取り込みを促進し、その働きによりCagAが示す発がん活性の亢進に寄与していることが強く示唆された。本研究から、SHIP2は特に欧米に広く分布するピロリ菌が持つCagAへの結合が強いことが示され、欧米型のcagA陽性ピロリ菌感染を起点とした胃発がんに関わることが推察された。SHIP2によるCagA取り込み促進のメカニズムをさらに詳細に明らかにすることで、胃がん発症予防に関わる重要な知見が得られる可能性がある。