| [ Summary ] |
CagA is delivered into epithelial cells by the type IV secretion system, where it is phosphorylated on tyrosine residues and wired to eukaryotic signal transduction pathways. Moreover, translocated CagA forms a physical complex with SHP-2, which is known to play an important positive role in mitogenic signal transduction. Based on the sequence constituting the SHP-2 binding site, CagA proteins can be subclassified into East Asian and Western types. East Asian type CagA possesses stronger SHP-2 binding and transforming activities than Western type CagA. In addition, VacA causes massive cellular vacuolation in vitro and gastric tissue damage in vivo, leading to gastric ulcers, when administered intragastrically. Mice deficient in Ptprz do not show mucosal damage by VacA. The binding of VacA to Ptprz induces marked detachment of gastric epithelial cells from basement membranes. These findings suggest that CagA and VacA are major virulent factors for gastric mucosa damage. |