SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein

• DOI: 10.1126/science.1067147
• Publication Date: 2002-07-27T09:47:15Z
• Authors: Hideaki Higashi; Ryouhei Tsutsumi; Syuichi Muto; Toshiro Sugiyama; Takeshi Azuma; Masahiro Asaka; Masanori Hatakeyama
• Keywords: Antigens, Bacterial; 0303 health sciences; Helicobacter pylori; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Cell Membrane; Intracellular Signaling Peptides and Proteins; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Dipeptides; 03 medical and health sciences; Phenotype; Amino Acid Substitution; Bacterial Proteins; Gastric Mucosa; COS Cells; Mutation; Animals; Humans; Enzyme Inhibitors; Phosphorylation; Protein Tyrosine Phosphatases; Phosphotyrosine; Cell Size

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.