{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:44:33Z","timestamp":1790297073212,"version":"4.1.0"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,11,7]]},"abstract":"<jats:p>CagA protein is a major virulence factor of Helicobacter pylori, which is delivered into gastric epithelial cells and elicits growth factor\u2013like 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\u2013induced scattering of gastric epithelial cells in culture was blocked by overexpression of dominant-negative Crk and by RNA interference\u2013mediated knockdown of endogenous Crk. H. pylori infection of the gastric epithelium induced disruption of E-cadherin\/catenin\u2013containing 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.<\/jats:p>","DOI":"10.1084\/jem.20051027","type":"journal-article","created":{"date-parts":[[2005,11,7]],"date-time":"2005-11-07T20:03:02Z","timestamp":1131393782000},"page":"1235-1247","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":193,"title":["Interaction of CagA with Crk plays an important role in <i>Helicobacter pylori<\/i>\u2013induced loss of gastric epithelial cell adhesion"],"prefix":"10.1084","volume":"202","author":[{"given":"Masato","family":"Suzuki","sequence":"first","affiliation":[{"name":"1Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Mimuro","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morag","family":"Park","sequence":"additional","affiliation":[{"name":"4Molecular Oncology Group, McGill University Hospital Center, McGill University, Montreal, Quebec H3A 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"2Department of Cancer Biology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Sasakawa","sequence":"additional","affiliation":[{"name":"1Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"},{"name":"3Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan"},{"name":"5Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 332-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,11,7]]},"reference":[{"key":"2023072513315810000_BIB1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mib.2004.12.004","volume":"8","year":"2005","journal-title":"Curr. 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