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

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

Research output: Contribution to journal › Article › peer-review

752 Citations (Scopus)

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.

Original language	English
Pages (from-to)	683-686
Number of pages	4
Journal	Science
Volume	295
Issue number	5555
DOIs	https://doi.org/10.1126/science.1067147
Publication status	Published - 2002 Jan 25
Externally published	Yes

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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.",

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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

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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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