SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein-Reference-Cited by-同舟云学术

SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein

Published:2002-01-25 Issue:5555 Volume:295 Page:683-686
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Higashi Hideaki¹,Tsutsumi Ryouhei¹,Muto Syuichi¹,Sugiyama Toshiro²,Azuma Takeshi³,Asaka Masahiro²,Hatakeyama Masanori¹

Affiliation:

1. Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan.

2. Department of Gastroenterology & Hematology, Graduate School of Medicine, Hokkaido University, Sapporo 060-0815, Japan.

3. The Second Department of Internal Medicine, Fukui Medical University, Fukui 910-1193, Japan.

Abstract

Helicobacter pylori CagA protein is associated with severe gastritis and gastric carcinoma. CagA is injected from the attached Helicobacter pylori into host cells and undergoes tyrosine phosphorylation. Wild-type but not phosphorylation-resistant CagA induced a growth factor–like response in gastric epithelial cells. Furthermore, CagA formed a physical complex with the SRC homology 2 domain (SH2)–containing tyrosine phosphatase SHP-2 in a phosphorylation-dependent manner and stimulated the phosphatase activity. Disruption of the CagA–SHP-2 complex abolished the CagA-dependent cellular response. Conversely, the CagA effect on cells was reproduced by constitutively active SHP-2. Thus, upon translocation, CagA perturbs cellular functions by deregulating SHP-2.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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