Helicobacter pylori is a prevalent human parasite (infecting half the world's population) and is linked to a variety of gut disorders, including severe gastritis and gastric carcinoma. Higashi et al. have elucidated the steps taken by the bacterial CagA protein that transform host cells. After CagA protein is injected by H. pylori into host cells, it is phosphorylated on tyrosine residues by host kinases. Phosphorylated CagA then binds to the Src homology 2 (SH2) domain-containing tyrosine phosphatase (SHP-2), which stimulates SHP-2 translocation to the cell surface where it displays its phosphatase activity. Active membrane-associated SHP-2 then stimulates morphological changes in the host cell that are the prelude to cellular transformation.
H. Higashi, R. Tsutsumi, S. Muto, T. Sugiyama, T. Azuma, M. Asaka, M. Hatakeyama, SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295, 683-686 (2002). [Abstract] [Full Text]