Gene, Cell and Tissue

Published by: Kowsar

Evaluation of Cell- Morphological Changes by Helicobacter pylori CagA and Pragmin in AGS Human Gastric Carcinoma Cells

Fatemeh Safari 1 , 2 , * and Sheyda Jodeiry Zaer 2
Authors Information
1 Division of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
2 Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
Article information
  • Gene, Cell and Tissue: April 2017, 4 (2); e12598
  • Published Online: April 29, 2017
  • Article Type: Research Article
  • Received: February 6, 2017
  • Revised: March 14, 2017
  • Accepted: April 4, 2017
  • DOI: 10.5812/gct.12598

To Cite: Safari F, Jodeiry Zaer S. Evaluation of Cell- Morphological Changes by Helicobacter pylori CagA and Pragmin in AGS Human Gastric Carcinoma Cells, Gene Cell Tissue. 2017 ; 4(2):e12598. doi: 10.5812/gct.12598.

Copyright © 2017, Gene, Cell and Tissue. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin. 2005; 55(2): 74-108[DOI]
  • 2. Kuipers EJ, Perez-Perez GI, Meuwissen SG, Blaser MJ. Helicobacter pylori and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst. 1995; 87(23): 1777-80[DOI][PubMed]
  • 3. Peek RJ, Miller GG, Tham KT, Perez-Perez GI, Zhao X, Atherton JC, et al. Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest. 1995; 73(6): 760-70[PubMed]
  • 4. Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993; 90(12): 5791-5[DOI][PubMed]
  • 5. Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997; 388(6642): 539-47[DOI][PubMed]
  • 6. Covacci A, Rappuoli R. Tyrosine-phosphorylated bacterial proteins: Trojan horses for the host cell. J Exp Med. 2000; 191(4): 587-92[DOI][PubMed]
  • 7. Poppe M, Feller SM, Romer G, Wessler S. Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene. 2007; 26(24): 3462-72[DOI][PubMed]
  • 8. Tammer I, Brandt S, Hartig R, Konig W, Backert S. Activation of Abl by Helicobacter pylori: a novel kinase for CagA and crucial mediator of host cell scattering. Gastroenterology. 2007; 132(4): 1309-19[DOI][PubMed]
  • 9. Hatakeyama M. Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer. 2004; 4(9): 688-94[DOI][PubMed]
  • 10. Backert S, Tegtmeyer N, Selbach M. The versatility of Helicobacter pylori CagA effector protein functions: The master key hypothesis. Helicobacter. 2010; 15(3): 163-76[DOI][PubMed]
  • 11. Tsutsumi R, Higashi H, Higuchi M, Okada M, Hatakeyama M. Attenuation of Helicobacter pylori CagA x SHP-2 signaling by interaction between CagA and C-terminal Src kinase. J Biol Chem. 2003; 278(6): 3664-70[DOI][PubMed]
  • 12. Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 2002; 295(5555): 683-6[DOI][PubMed]
  • 13. Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A. 2002; 99(22): 14428-33[DOI][PubMed]
  • 14. Selbach M, Paul FE, Brandt S, Guye P, Daumke O, Backert S, et al. Host cell interactome of tyrosine-phosphorylated bacterial proteins. Cell Host Microbe. 2009; 5(4): 397-403[DOI][PubMed]
  • 15. Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T, Sasakawa C. Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med. 2005; 202(9): 1235-47[DOI][PubMed]
  • 16. Bourzac KM, Botham CM, Guillemin K. Helicobacter pylori CagA induces AGS cell elongation through a cell retraction defect that is independent of Cdc42, Rac1, and Arp2/3. Infect Immun. 2007; 75(3): 1203-13[DOI][PubMed]
  • 17. Segal ED, Cha J, Lo J, Falkow S, Tompkins LS. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci U S A. 1999; 96(25): 14559-64[DOI][PubMed]
  • 18. Selbach M, Moese S, Hurwitz R, Hauck CR, Meyer TF, Backert S. The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivation. EMBO J. 2003; 22(3): 515-28[DOI][PubMed]
  • 19. Safari F, Murata-Kamiya N, Saito Y, Hatakeyama M. Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectors. Proc Natl Acad Sci U S A. 2011; 108(36): 14938-43[DOI][PubMed]
  • 20. Senda Y, Murata-Kamiya N, Hatakeyama M. C-terminal Src kinase-mediated EPIYA phosphorylation of Pragmin creates a feed-forward C-terminal Src kinase activation loop that promotes cell motility. Cancer Sci. 2016; 107(7): 972-80[DOI][PubMed]
  • 21. Leroy C, Fialin C, Sirvent A, Simon V, Urbach S, Poncet J, et al. Quantitative phosphoproteomics reveals a cluster of tyrosine kinases that mediates SRC invasive activity in advanced colon carcinoma cells. Cancer Res. 2009; 69(6): 2279-86[DOI][PubMed]
  • 22. Tactacan CM, Phua YW, Liu L, Zhang L, Humphrey ES, Cowley M, et al. The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling. Mol Cancer. 2015; 14: 139[DOI][PubMed]
  • 23. Selbach M, Moese S, Backert S, Jungblut PR, Meyer TF. The Helicobacter pylori CagA protein induces tyrosine dephosphorylation of ezrin. Proteomics. 2004; 4(10): 2961-8[DOI][PubMed]
  • 24. Moese S, Selbach M, Brinkmann V, Karlas A, Haimovich B, Backert S, et al. The Helicobacter pylori CagA protein disrupts matrix adhesion of gastric epithelial cells by dephosphorylation of vinculin. Cell Microbiol. 2007; 9(5): 1148-61[DOI][PubMed]
  • 25. Tegtmeyer N, Wittelsberger R, Hartig R, Wessler S, Martinez-Quiles N, Backert S. Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori. Cell Host Microbe. 2011; 9(6): 520-31[DOI][PubMed]
  • 26. Tsutsumi R, Takahashi A, Azuma T, Higashi H, Hatakeyama M. Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. Mol Cell Biol. 2006; 26(1): 261-76[DOI][PubMed]
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