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Intracellular signal transduction mechanism and morbit state on the interaction between H. pylori and host cells

Research Project

Project/Area Number 10670148
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionFukui Prefectural University (1999)
Fukui Prefectural College (1998)

Principal Investigator

ASAHI Momoyo  Fukui Prefectural University, the Faculty of Nursing and Welfare, Assistant Professor, 看護福祉学部, 助教授 (60100624)

Co-Investigator(Kenkyū-buntansha) KATO Takuji  Fukui Prefectural University, the Faculty of Nursing and Welfare, Professor, 看護福祉学部, 教授 (70145902)
NAGAI Yukifumi  Fukui Medical University, the Department of Biology, Professor, 看護福祉学部, 教授 (80135102)
AZUMA Takesi  Fukui Medical University, the Second Department of Internal Medicine, Lecturer, 医学部, 講師 (60221040)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsH. pylori / CagA protein / Protein-tyrosine phosphorylation / AGS cells / MKN45 cells / Phathogenicity island (PAI) / src-tyrosine kinase / EGF receptor-tyrosine kinase / H.Pylori / MKN 45 cell / AGS cell / 蛋白質チロシンリン酸化 / 145kDa蛋白質
Research Abstract

Attachment of Helicobacter pylori to gastric epithelial cells induces various cellular responses, including the tyrosine phosphorylation of an unknown 145-kD protein and interleukin 8 production. Here we show that this 145-kD protein is the cagA product of H. pylori, an immunodominant, cytotoxin-associated antigen. Epithelial cells infected with various H. pylori clinical isolates resulted in generation of tyrosine-phosphorylated proteins ranging from 130 to 145 kD in size that were also induced in vitro by mixing host cell lysate with bacterial lysate. When epithelial cells were infected with [(35)S]methionine-labeled H. pylori, a radioactive 145-kD protein was detected in the immunoprecipitates with antiphosphotyrosine antibody or anti-CagA (cytotoxin-associated gene A) antibody. Consistently, the 145-kD protein recognized by the anti-CagA and antiphosphotyrosine antibodies was induced in epithelial cells after infection of wild-type H. pylori but not the cagA :: Km mutant. furthermore, the amino acid sequence of the phosphorylated 145-kD protein induced by H. pylori infection was identical to the H. pylori CagA sequence. These results reveal that the tyrosine-phosphorylated 145-kD protein is H. pylori CagA protein, which may be delivered from attached bacteria into the host cytoplasm. The identification of the tyrosine-phosphorylated protein will thus provide further insights into understanding the precise roles of CagA protein in H. pylori pathogenesis.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Asahi M., Azuma T., Ito S., Ito Y., Suto H., Nagai Y., Tsubolawa M., Tohyama Y., Maeda S., Omata M. Suzuki T., Sasakawa C.: "Hericobacter pylori can be tyrosine phosphoryation in gastric ipithelial cells"191(4). 593-602 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tohyama Y., Tohyama K., Tsubokawa M., Asahi M., Yoshida Y., Yamamura H.: "outside-in signaling of soluble and solid fibrinogen through integrin αIIbβ 3 is di stinguished and cooperative with each other in a megaharyoblastic leukemia cell line CMK"Blood. 92(4). 1277-1286 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito Y, Azuma T, Ito S, Suto H, Miyaji H, Yamazaki Y, Kato T, Kohli Y, Keida Y, Kuriyama M: "Sequence analysis and clinical significance of the iceA gene from Helicobacter"J Clin Microbiol. 38(2). 483-488 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto H, Azuma T, Ito Y, Miyaji H, Yamazaki Y, Kohli Y, Kuriyama M: "Evaluation of endoscopic 13C-urea breath test for assenssment of Helicobacter pylori eradication"J. Gastroenterol. 34. 67-71 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyaji H, Azuma T, Ito S, Abe Y., Ono H, Suto H, Ito Y, Yamazaki Y, Kohli Y, Kuriyama M: "The effect of helicobacter pylori eradication therapy on gastric antral myoekectrical activity andgastric emptying in patients with non-ulcer dyspepsia"Aliment Pharmacol Ther. 13(11). 1473-1480 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 朝日百百代: "日経Continuing Medical Education(11月別冊)・・・世界消化器病学会会議(WCOG'98)特集・・・H.pyloriの接着により胃癌細胞のチロシンリン酸化を抑制"日経メディカル開発社. 8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Asahi M., Azuma T., Ito S., Ito Y., Suto H., Nagai Y., Tsubokawa M., Tohyama Y., Maeda S., Omata M., Suzuki T., Sasakawa C.: "Hericobacter pylori can be tyrosine phosphorylation in gastric epithelial cells"J. Exp. Med.. 191(4). 593-602 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tohyama Y., tohyama K., Tsubokawa M., Asahi M., yoshida Y., Yamamura H.: "Outside-in signaling of soluble and solid fibrinogen through integrin αIIbβ3 is distinguished and cooperative with each other in a megakaryoblastic leukemia cell line, CMK"Blood. 92(4). 1277-1286 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito Y, Azuma T, Ito S, Suto H, Miyaji H, Yamazaki Y, Kato T, Kohli Y, Keida Y, Kuriyama M: "Sequence analysis and clinical significance of the iceA gene from Helicobacter pylori strains in Japan.."j Clin Microbiol. 38(2). 483-488 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto H, Azuma T, Ito S, Ito Y, Miyaji H, Yamazaki Y, Kohli Y, Kuriyama M: "Evaluation of endoscopic 13C-urea breath test for assessment of Helicobacter pylori eradication."J. Gastroenterol. 34. 67-71 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyaji H, Azuma T, Ito S, Abe Y, Ono H, Suto H Ito Y, Yamazaki Y, Kohli Y, Kuriyama M: "The effect of helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia."Aliment Pharmacol Ther. 13(11). 1473-1480 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Asahi M: "A special edition of World Congresses of Gastroenterolog '98 -Inhibition of tyrosinephosphorylation induced by adhesion of H. pylori in gastric cancer cells-"Nikkei Continuing Medical Education. Nov. 10. 1-8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Asahi M., Azuma T., Ito S., Ito Y., Suto H., Nagai Y., Tsubokawa M., Tohyama Y., Maeda S., Omata M., Suzuki T., Sasakawa C.: "Hericobacter pylori can be tyrosine phosphorylation in gastric epithelial cells"J. Exp. Med.. 191(4). 593-602 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tohyama Y., Tohyama K., Tsubokawa M., Asahi M., Yoshida Y., Yamamura H.,: "Outside-in signaling of soluble and solid fibrinogen through integrin αIIbβ3 is di stinguished and cooperative with each other in a megakaryoblastic leukemia cell line CMK"Blood. 92(4). 1277-1286 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 朝日百百代: "日経Continuing Medical Education(11月別冊)---世界消化器病学会会議(WCOG'98)特集---H.pyloriの接着による胃癌細胞のチロシンリン酸化を抑制-----"日経メデイカル開発社. 8 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Asahi,T.Kato,S.Ito,T.Azuma,M.Aihara,Y.Tohyama,Y.Nagai: "“Diversity of protein-tyrosine phosphorylation induced with various strains of Helicobacter pylori infection in gastric cell lines" Gut. Vol.43(2). 30-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 朝日百百代: "「H.Pyloriの接着による胃癌細胞のチロシンリン酸化を抑制」" 日経CME. 11月別冊. 6-6 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Tohyama,K.Tohyama,M.Tsubokawa,M.Asahi,Y.Yoshida,H.Yamamura.: "“Outside-in signaling of soluble and solid fibrinogen through integrin α IIbβ 3 is distin-guished and cooperative with each other in a mega karyoblastic leukemia cell line CMK"" Blood. Vol.92(4). 1277-1286 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Okishio,R.Fukuda,M.Nagai,Y.Nagai,S.Nagatomo,T.Kitagawa: "“Tyrosine Phosphorylation- induced changes in absorption and UV resonance Raman spectra of Src-peptides"" J.Raman Spectroscopy. 29. 31-39 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Azuma,S.Ito,F.Sato,Y.Yamazaki,H.Miyaji,Y.Ito,H.Suto,M.Kuriyama,T.Kato,Y.Kohli.: "“The role of the HLA-DQA1 gene in resistance to atrophic gastritis and gastric adenocarcinoma induced by Helicobacter pylori infection."" Cancer. 82. 1013-1018 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Ito,T.Azuma,S.Ito,H.Suto,H.Miyaji,Y.Yamzaki,Y.Kohli,M.Kuriyama.: "“Full-length sequence analysis of the vacA gene from cytotoxic and noncytotoxic Helicobacter pylori."" J.Infectious Diseases. 178. 1391-1398 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2025-11-20  

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