論文 - 詳細
| RRC ID | 1181 |
|---|---|
| 著者 | Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T, Sasakawa C. |
| タイトル | Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. |
| ジャーナル | 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. |
| 巻・号 | 202(9) |
| ページ | 1235-47 |
| 公開日 | 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 |
| 引用数 | 159 |
| WOS 分野 | IMMUNOLOGY MEDICINE, RESEARCH & EXPERIMENTAL |
| リソース情報 | |
| 病原微生物 | |