Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation.
Helicobacter pylori strains associated with severe tissue damage and inflammation possess a unique genetic locus, cag, containing 31 genes originating from a distant event of horizontal transfer and retained as a pathogenicity island. The cag system is an Helicobacter-specific type IV secretion engine involved in cellular responses like induction of pedestals, secretion of IL-8, and phosphorylation of proteic targets. It has previously been reported that cocultivation of epithelial cells with Helicobacter pylori triggers signal transduction and tyrosine phosphorylation of a 145-kDa putative host cell protein. Herein, we demonstrate that this protein is not derived from the host but rather is the bacterial immunodominant antigen CagA, a virulence factor commonly expressed in peptic ulcer disease and thought to be an orphan of a specific biological function. Thus, CagA is delivered into the epithelial cells by the cag type IV secretion system where it is phosphorylated on tyrosine residues by an as yet unidentified host cell kinase and wired to eukaryotic signal transduction pathways and cytoskeletal plasticity.
Stein
M
M
Immunobiological Research Institute of Siena, Chiron SpA, Via Fiorentina 1, 53100 Siena, Italy.
Rappuoli
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Covacci
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D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases