OipA plays a role in Helicobacter pylori-induced focal adhesion kinase activation and cytoskeletal re-organization.
The initial signalling events leading to Helicobacter pylori infection associated changes in motility, cytoskeletal reorganization and elongation of gastric epithelial cells remain poorly understood. Because focal adhesion kinase (FAK) is known to play important roles in regulating actin cytoskeletal organization and cell motility we examined the effect of H. pylori in gastric epithelial cells co-cultured with H. pylori or its isogenic cag pathogenicity island (PAI) or oipA mutants. H. pylori induced FAK phosphorylation at distinct tyrosine residues in a dose- and time-dependent manner. Autophosphorylation of FAK Y397 was followed by phosphorylation of Src Y418 and resulted in phosphorylation of the five remaining FAK tyrosine sites. Phosphorylated FAK and Src activated Erk and induced actin stress fibre formation. FAK knock-down by FAK-siRNA inhibited H. pylori-mediated Erk phosphorylation and abolished stress fibre formation. Infection with oipA mutants reduced phosphorylation of Y397, Y576, Y577, Y861 and Y925, inhibited stress fibre formation and altered cell morphology. cag PAI mutants reduced phosphorylation of only FAK Y407 and had less effect on stress fibre formation than oipA mutants. We propose that activation of FAK and Src are responsible for H. pylori-induced induction of signalling pathways resulting in the changes in cell phenotype important for pathogenesis.
Tabassam
Fazal H
FH
Department of Medicine/Gastroenterology, Michael DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.
Graham
David Y
DY
Yamaoka
Yoshio
Y
D000199:Actins / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D009154:Mutation; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D001425:Bacterial Outer Membrane Proteins; C526444:OipA protein, Helicobacter pylori; D034741:RNA, Small Interfering; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases