SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein.
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.
Higashi
Hideaki
H
Division of Molecular Oncology, Institute for Genetic Medicine and Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan.
Tsutsumi
Ryouhei
R
Muto
Syuichi
S
Sugiyama
Toshiro
T
Azuma
Takeshi
T
Asaka
Masahiro
M
Hatakeyama
Masanori
M
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
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