Helicobacter pylori stimulates epithelial cell migration via CagA-mediated perturbation of host cell signaling.
Helicobacter pylori CagA is delivered into gastric epithelial cells, where undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif to interact with Src homology 2-containing protein tyrosine phosphatase-2 (SHP2) oncoprotein. CagA also binds to partitioning-defective 1 (PAR1) polarity-regulating kinase via the CagA multimerization (CM) sequence. To investigate pathophysiological role of CagA-SHP2 and/or CagA-PAR1 interaction in H. pylori infection, we generated H. pylori isogenic strains producing a phosphorylation-resistant CagA and a CagA without CM sequence. Infection studies revealed that deregulation of epithelial cell motility was more prominent in the wild-type strain than in the mutant strains. Thus, both CagA-SHP2 and CagA-PAR1 interactions are involved in the pathogenicity of cagA-positive H. pylori.
Division of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Kenji
K
Kikuchi
Naoko
N
Murata-Kamiya
Satoshi
S
Kondo
Masanori
M
Hatakeyama
D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori; C111833:MARK3 protein, human; D017346:Protein Serine-Threonine Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11