The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa.
Recent experiments have indicated that CagA of Helicobacter pylori is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in cells and that translocated CagA binds the SRC homology 2 domain-containing tyrosine phosphatase (SHP-2). We investigated these phenomena in in vivo human gastric mucosa. Tyrosine-phosphorylated CagA and CagA-coimmunoprecipitated SHP-2 were detected in gastric mucosa from H. pylori-positive patients with atrophic gastritis and in noncancerous tissues from H. pylori-positive patients with early gastric cancer. In contrast, CagA was not detected in gastric mucosa with either intestinal metaplasia or cancer. Our results provide the first evidence that CagA is translocated into the gastric epithelial cells, receives tyrosine phosphorylation, and binds SHP-2 in in vivo human gastric mucosa. Deregulation of SHP-2 by CagA may play a role in the acquisition of a cellular-transformed phenotype at a relatively early stage of multistep gastric carcinogenesis.
Yamazaki
Shiho
S
Second Department of Internal Medicine, Fukui Medical University, Japan.
Yamakawa
Akiyo
A
Ito
Yoshiyuki
Y
Ohtani
Masahiro
M
Higashi
Hideaki
H
Hatakeyama
Masanori
M
Azuma
Takeshi
T
D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D005757:Gastritis, Atrophic / Q000201:enzymology / Q000209:etiology / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000209:etiology / Q000382:microbiology / Q000473:pathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D047908:Intracellular Signaling Peptides and Proteins; C080866:cagA protein, Helicobacter pylori; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases