EPIYA Motif Is a Membrane-targeting Signal ofHelicobacter pyloriVirulence Factor CagA in Mammalian Cells

摘要: Helicobacter pylori contributes to the development of peptic ulcers and atrophic gastritis. Furthermore, H. strains carrying cagA gene are more virulent than cagA-negative associated with gastric adenocarcinoma. The product, CagA, is translocated into epithelial cells localizes inner surface plasma membrane, in which it undergoes tyrosine phosphorylation at Glu-Pro-Ile-Tyr-Ala (EPIYA) motif. Tyrosine-phosphorylated CagA specifically binds activates Src homology 2-containing protein-tyrosine phosphatase-2 (SHP-2) thereby inducing an elongated cell shape termed hummingbird phenotype. Accordingly, membrane tethering essential prerequisite for pathogenic activity CagA. We show here that association requires EPIYA-containing region but independent EPIYA phosphorylation. further specific deletion motif abolishes ability associate membrane. Conversely, reintroduction sequence a mutant lacks restores Thus, presence single necessary localization Our results indicate has dual function phosphorylation, both critically involved deregulate intracellular signaling, suggest crucial therapeutic target cagA-positive infection.