title: SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein.
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.
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Higashi
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Tsutsumi
authors.forename: Syuichi
authors.initials: S
authors.lastname: Muto
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatakeyama
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D048429:Cell Size; D004151:Dipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology*; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D014162:Transfection; D014774:Virulence; D018909:src Homology Domains
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004151:Dipeptides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; C080866:cagA protein, Helicobacter pylori; C071482:calpeptin; D019000:Phosphotyrosine; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases