CagA tyrosine phosphorylation in gastric epithelial cells caused by Helicobacter pylori in patients with gastric adenocarcinoma.
BACKGROUND
Tyrosine phosphorylation of Helicobacter pylori cytotoxin-associated protein of in gastric epithelial cells is reported. The goals of this study are first to examine the occurrence of CagA tyrosine phosphorylation in H. pylori strains isolated from patients with gastric adenocarcinoma and gastritis, and second to clarify the relationship between the diversity of tyrosine phosphorylation motifs and the presence of CagA tyrosine phosphorylation.


METHODS
Fifty-eight clinical isolates of H. pylori from patients with gastric adenocarcinoma (29 cases) and gastritis (29 cases) were studied for CagA tyrosine phosphorylation by Western blotting. Sequence diversity of tyrosine phosphorylation motifs was analysed among positive- or negative-CagA tyrosine phosphorylation isolates.


RESULTS
Positive CagA tyrosine phosphorylation was found in 93.1% (27 of 29) of strains from gastric adenocarcinoma patients and 51.7% (15 of 29) of strains from gastritis patients (p < 0.001). Intact motifs were found in H. pylori isolates with CagA tyrosine phosphorylation. Of the 16 negative CagA tyrosine phosphorylation isolates, intact tyrosine phosphorylation motifs were found in 15 isolates.


CONCLUSIONS
CagA tyrosine phosphorylation, which is significantly greater in strains from gastric adenocarcinoma patients, may play a role in gastric carcinogenesis, and could be a better marker of more virulent strains than the cag pathogenicity island in Asia, where the cag pathogenicity island is present in nearly all H. pylori strains. Sequence diversity of tyrosine phosphorylation motifs on CagA was not related to the presence of tyrosine phosphorylation. The absence of tyrosine phosphorylation motif might result in negative tyrosine phosphorylation phenotypes, but such motifs are not the sole factors associated with CagA tyrosine phosphorylation.
Lai
Yo-Ping
YP
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Yang
Jyh-Chin
JC
Lin
Tzu-Zung
TZ
Wang
Jin-Town
JT
Lin
Jaw-Town
JT
D000230:Adenocarcinoma / Q000378:metabolism* / Q000382:microbiology; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D013270:Stomach / Q000166:cytology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology; D014443:Tyrosine / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine