SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein

Hideaki Higashi; Ryouhei Tsutsumi; Syuichi Muto; Toshiro Sugiyama; Takeshi Azuma; Masahiro Asaka; Masanori Hatakeyama

doi:10.1126/science.1067147

SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein

Science. 2002 Jan 25;295(5555):683-6. doi: 10.1126/science.1067147. Epub 2001 Dec 13.

Authors

Hideaki Higashi¹, Ryouhei Tsutsumi, Syuichi Muto, Toshiro Sugiyama, Takeshi Azuma, Masahiro Asaka, Masanori Hatakeyama

Affiliation

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

PMID: 11743164
DOI: 10.1126/science.1067147

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.

Publication types

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

MeSH terms

Amino Acid Substitution
Animals
Antigens, Bacterial*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
COS Cells
Cell Membrane / enzymology
Cell Membrane / metabolism
Cell Size
Dipeptides / pharmacology
Enzyme Inhibitors / pharmacology
Gastric Mucosa / cytology
Gastric Mucosa / enzymology*
Helicobacter pylori* / genetics
Helicobacter pylori* / pathogenicity
Humans
Intracellular Signaling Peptides and Proteins
Mutation
Phenotype
Phosphorylation
Phosphotyrosine / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / antagonists & inhibitors
Protein Tyrosine Phosphatases / chemistry
Protein Tyrosine Phosphatases / genetics
Protein Tyrosine Phosphatases / metabolism*
Recombinant Fusion Proteins / metabolism
SH2 Domain-Containing Protein Tyrosine Phosphatases
Transfection
Virulence
src Homology Domains

Substances

Antigens, Bacterial
Bacterial Proteins
Dipeptides
Enzyme Inhibitors
Intracellular Signaling Peptides and Proteins
Recombinant Fusion Proteins
cagA protein, Helicobacter pylori
calpeptin
Phosphotyrosine
PTPN11 protein, human
PTPN6 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases
SH2 Domain-Containing Protein Tyrosine Phosphatases