Crossref journal-article
Rockefeller University Press
The Journal of Experimental Medicine (291)
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.

Bibliography

Suzuki, M., Mimuro, H., Suzuki, T., Park, M., Yamamoto, T., & Sasakawa, C. (2005). Interaction of CagA with Crk plays an important role in Helicobacter pylori–induced loss of gastric epithelial cell adhesion. The Journal of Experimental Medicine, 202(9), 1235–1247.

Authors 6
  1. Masato Suzuki (first)
  2. Hitomi Mimuro (additional)
  3. Toshihiko Suzuki (additional)
  4. Morag Park (additional)
  5. Tadashi Yamamoto (additional)
  6. Chihiro Sasakawa (additional)
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Dates
Type When
Created 19 years, 9 months ago (Nov. 7, 2005, 3:03 p.m.)
Deposited 2 years, 1 month ago (July 25, 2023, 9:33 a.m.)
Indexed 4 months, 1 week ago (April 28, 2025, 7:27 p.m.)
Issued 19 years, 9 months ago (Nov. 7, 2005)
Published 19 years, 9 months ago (Nov. 7, 2005)
Published Online 19 years, 9 months ago (Nov. 7, 2005)
Published Print 19 years, 9 months ago (Nov. 7, 2005)
Funders 0

None

@article{Suzuki_2005, title={Interaction of CagA with Crk plays an important role in Helicobacter pylori–induced loss of gastric epithelial cell adhesion}, volume={202}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20051027}, DOI={10.1084/jem.20051027}, number={9}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Suzuki, Masato and Mimuro, Hitomi and Suzuki, Toshihiko and Park, Morag and Yamamoto, Tadashi and Sasakawa, Chihiro}, year={2005}, month=nov, pages={1235–1247} }