The pathophysiological function of Helicobacter pylori CagA oncoprotein that is processed in gastric epithelial cells

• Project/Area Number: 23890037
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including Mycology)
• Research Institution: The University of Tokyo
• Principal Investigator: SAITO Yasuhiro 東京大学, 大学院・医学系研究科, 助教 (30613004)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 胃がん / ピロリ菌 / CagA / SHP2 / ヘリコバクター・ピロリ菌

Research Abstract

Infection of the cagA-positive Helicobacter pylori relates to the induction of gastric cancer. The cagA-positive H. pylori produces CagA protein in the bacterial cells and injects it into gastric epithelial cells. The translocated CagA targets SHP2 oncoprotein and deregulates the function of SHP2. The subcellular distribution of CagA in gastric epithelial cells was investigated in this study and CagA was observed in the nucleus as well as cytoplasmic membrane. Since nuclear SHP2 activates Wnt signaling, the results implicate that nuclear CagA aberrantly activates the Wnt pathway via deregulation of nuclear SHP2.

Research Products

• [Journal Article] Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulatRhoA-dependent actin cytoskeletal reorganization (2011)
  • Author(s): Yamahashi Y, Saito Y, Murata-Kamiya N, Hatakeyama M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 44576-44584
  • Peer Reviewed
• [Journal Article] Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulate RhoA-dependent actin cytoskeletal reorganization (2011)
  • Author(s): Yamahashi, Y.
  • Journal Title: J.Biol.Chem.2 Volume: 286 Issue: 52 Pages: 44576-44584
  • DOI: 10.1074/jbc.m111.267021
  • Peer Reviewed
• [Presentation] Interaction of the Helicobacter pylori CagA oncoprotein with SHP2 in the nucleus.核内における Helicobacter pylori CagA がん タンパク質 - SHP2 相互作用 (2012)
  • Author(s): 齊藤康弘、畠山昌則
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Involvement of multiple tyrosine kinases in antagonizing parafibromin-mediated activation of Wnt signaling by SHP2 複数のチロシンキナーゼによる SHP2/parafibromin 依存的 Wnt シグナル活性化の拮抗制御 (2012)
  • Author(s): 高橋昌史、齊藤康弘、畠山昌則
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Interaction of the Helicobacter pylori CagA oncoprotein with SHP2 in the nucleus (2012)
  • Author(s): 齊藤康弘
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館、札幌市
• [Presentation] Involvement of multiple tyrosine kinases in antagonizing parafibromin-mediated activation of Wnt signaling by SHP2 (2012)
  • Author(s): 高橋昌史
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館、札幌市
• [Presentation] Helicobacter pylori CagA oncoprotein targets epithelial polarity to elicit aberrant cell proliferation (2011)
  • Author(s): 齊藤康弘
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-05
• [Presentation] Pragmin is a human EPIYA-containing protein targeted by H.pylori CagA oncoprotein (2011)
  • Author(s): サファリファテメ
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-05
• [Presentation] Helicobacter pylori CagA oncoprotein targets epithelial polarity to elicit aberrant cell proliferation.Helicobacter pylori CagA は上皮細胞極性破 壊により異常な細胞増殖を誘導する (2011)
  • Author(s): 齊藤康弘、紙谷尚子、畠山昌則
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Pragmin is a human EPIYA-containing protein targeted by H. pylori CagA oncoprotein. 胃がん発症におけるヘリコバクター・ピロリ CagA とヒト Pragmin の EPIYA 配列を介し た競合作用の意義 (2011)
  • Author(s): サファリファテメ、紙谷尚子、齊藤康弘、畠山昌則
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋