The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa

Shiho Yamazaki; Akiyo Yamakawa; Yoshiyuki Ito; Masahiro Ohtani; Hideaki Higashi; Masanori Hatakeyama; Takeshi Azuma

doi:10.1086/367807

The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa

J Infect Dis. 2003 Jan 15;187(2):334-7. doi: 10.1086/367807. Epub 2002 Dec 19.

Authors

Shiho Yamazaki¹, Akiyo Yamakawa, Yoshiyuki Ito, Masahiro Ohtani, Hideaki Higashi, Masanori Hatakeyama, Takeshi Azuma

Affiliation

¹ Second Department of Internal Medicine, Fukui Medical University, Japan.

PMID: 12552462
DOI: 10.1086/367807

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Bacterial*
Bacterial Proteins / metabolism*
Epithelial Cells / metabolism*
Gastric Mucosa / metabolism*
Gastritis, Atrophic / enzymology
Gastritis, Atrophic / etiology
Gastritis, Atrophic / microbiology
Gastritis, Atrophic / pathology
Helicobacter Infections / enzymology
Helicobacter Infections / metabolism
Helicobacter Infections / microbiology
Helicobacter Infections / pathology
Helicobacter pylori / metabolism*
Helicobacter pylori / pathogenicity
Humans
Intracellular Signaling Peptides and Proteins
Phosphorylation
Protein Binding
Protein Transport
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases / metabolism*
Stomach Neoplasms / enzymology
Stomach Neoplasms / etiology
Stomach Neoplasms / microbiology
Stomach Neoplasms / pathology

Substances

Antigens, Bacterial
Bacterial Proteins
Intracellular Signaling Peptides and Proteins
cagA protein, Helicobacter pylori
PTPN11 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases