Project/Area Number |
10670148
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathological medical chemistry
|
Research Institution | Fukui 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)
|
Keywords | H. 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.
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