Open AccessTyrosine phosphorylation of theHelicobacter pyloriCagA antigen aftercag-driven host cell translocation
Author(s) -
Markus Stein,
Rino Rappuoli,
Antonello Covacci
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.3.1263
Subject(s) - caga , biology , secretion , helicobacter pylori , tyrosine phosphorylation , phosphorylation , signal transduction , virulence factor , microbiology and biotechnology , virulence , gene , genetics , biochemistry
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.