The CagA Protein ofHelicobacter pyloriIs Translocated into Epithelial Cells and Binds to SHP‐2 in Human Gastric Mucosa | Zendy

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

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The CagA Protein ofHelicobacter pyloriIs Translocated into Epithelial Cells and Binds to SHP‐2 in Human Gastric Mucosa

Author(s) -

Shiho Yamazaki,

Akiyo Yamakawa,

Yoshiyuki Ito,

Masahiro Ohtani,

Hideaki Higashi,

Masanori Hatakeyama,

Takeshi Azuma

Publication year - 2003

Publication title -

the journal of infectious diseases

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.69

H-Index - 252

eISSN - 1537-6613

pISSN - 0022-1899

DOI - 10.1086/367807

Subject(s) - caga , gastric mucosa , helicobacter pylori , protein tyrosine phosphatase , biology , tyrosine phosphorylation , intestinal metaplasia , tyrosine , secretion , sh2 domain , foveolar cell , cancer research , stomach , biochemistry , gene , genetics , virulence

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.

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