TY - JOUR
T1 - SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein
AU - Higashi, Hideaki
AU - Tsutsumi, Ryouhei
AU - Muto, Syuichi
AU - Sugiyama, Toshiro
AU - Azuma, Takeshi
AU - Asaka, Masahiro
AU - Hatakeyama, Masanori
PY - 2002/1/25
Y1 - 2002/1/25
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1067147
DO - 10.1126/science.1067147
M3 - Article
C2 - 11743164
AN - SCOPUS:0037169076
VL - 295
SP - 683
EP - 686
JO - Science
JF - Science
SN - 0036-8075
IS - 5555
ER -