RRC ID 1181
Author Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T, Sasakawa C.
Title Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion.
Journal J Exp Med
Abstract CagA protein is a major virulence factor of Helicobacter pylori, which is delivered into gastric epithelial cells and elicits growth factor-like responses. Once within the cells, CagA is tyrosine phosphorylated by Src family kinases and targets host proteins required to induce the cell responses. We show that the phosphorylated CagA binds Crk adaptor proteins (Crk-II, Crk-I, and Crk-L) and that the interaction is important for the CagA-mediated host responses during H. pylori infection. H. pylori-induced scattering of gastric epithelial cells in culture was blocked by overexpression of dominant-negative Crk and by RNA interference-mediated knockdown of endogenous Crk. H. pylori infection of the gastric epithelium induced disruption of E-cadherin/catenin-containing adherens junctions, which was also dependent on CagA/Crk signaling. Furthermore, inhibition of the SoS1/H-Ras/Raf1, C3G/Rap1/B-Raf, or Dock180/Rac1/Wiskott-Aldrich syndrome protein family verprolin homologous protein pathway, all of which are involved downstream of Crk adaptors, greatly diminished the CagA-associated host responses. Thus, CagA targeting of Crk plays a central role in inducing the pleiotropic cell responses to H. pylori infection that cause several gastric diseases, including gastric cancer.
Volume 202(9)
Pages 1235-47
Published 2005-11-7
DOI 10.1084/jem.20051027
PII jem.20051027
PMID 16275761
PMC PMC2213224
MeSH Adaptor Proteins, Signal Transducing / physiology Animals Antigens, Bacterial / metabolism Antigens, Bacterial / physiology* Bacterial Proteins / metabolism Bacterial Proteins / physiology* Cell Adhesion / immunology Cell Communication / immunology Cell Line, Tumor Dogs ErbB Receptors / physiology Gastric Mucosa / immunology Gastric Mucosa / microbiology* Gastric Mucosa / pathology* Helicobacter Infections / metabolism* Helicobacter pylori / immunology* Humans Phenotype Phosphoproteins / physiology Phosphorylation Proto-Oncogene Proteins c-crk / metabolism Proto-Oncogene Proteins c-crk / physiology* Proto-Oncogene Proteins c-met / physiology Signal Transduction / immunology Stomach Neoplasms / immunology Stomach Neoplasms / microbiology Stomach Neoplasms / pathology Wiskott-Aldrich Syndrome Protein Family / physiology
IF 11.743
Times Cited 159
WOS Category IMMUNOLOGY MEDICINE, RESEARCH & EXPERIMENTAL
Resource
Pathogenic microorganisms ?