SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein
H Higashi, R Tsutsumi, S Muto, T Sugiyama, T Azuma… - Science, 2002 - science.org
H Higashi, R Tsutsumi, S Muto, T Sugiyama, T Azuma, M Asaka, M Hatakeyama
Science, 2002•science.orgHelicobacter 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 …
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 …
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.
AAAS