Tyrosine phosphorylation of CagA from Chinese Helicobacter pylori isolates in AGS gastric epithelial cells.
Helicobacter pylori strains possessing the cag pathogenicity island (PaI) are associated with the development of gastroduodenal diseases, including gastric cancer. cag PaI products induce the secretion of interleukin-8 (IL-8) from epithelial cells and facilitate the translocation of CagA into the cell cytosol. In East Asia, where the incidence of gastric cancer is high, most strains possess the cag PaI. To date, however, no cag PaI phenotypic data have been provided for strains isolated in mainland China. Here we used 31 Chinese strains to determine the genotypic and phenotypic status of the cag PaI. All strains possessed cagA and cagE, and we observed a variation in the length of cagA variable regions. Nucleotide sequencing of the cagA variable region revealed that CagA was of two types, a short "Western" form with two tyrosine phosphorylation sites and a longer "East Asian" form with three tyrosine phosphorylation sites. Coculture of strains with AGS epithelial cells showed that strains could induce IL-8 secretion from the cells and that CagA with three phosphorylation sites became more phosphorylated than that with two and could induce significantly (P < 0.001) more cells to elongate. We hypothesize that the preponderance of the more active East Asian form of cagA may underlie the high rate of gastric cancer in China.
Zhang
Youli
Y
Division of Gastroenterology, The Affiliated Hospital Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Argent
Richard H
RH
Letley
Darren P
DP
Thomas
Rachael J
RJ
Atherton
John C
JC
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002681:China; D004847:Epithelial Cells; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017422:Sequence Analysis, DNA; D013270:Stomach / Q000166:cytology / Q000382:microbiology*; D013274:Stomach Neoplasms / Q000382:microbiology; D014443:Tyrosine / Q000378:metabolism*; D014774:Virulence
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine