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Glowinski F, Holland C, Thiede B, et al. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics. Front Microbiol. 2014;5:356doi: 10.3389/fmicb.2014.00356.
Glowinski, F., Holland, C., Thiede, B., Jungblut, P. R., & Meyer, T. F. (2014). Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics. Frontiers in microbiology, 5356. https://doi.org/10.3389/fmicb.2014.00356
Glowinski, Frithjof, et al. "Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics." Frontiers in microbiology vol. 5 (2014): 356. doi: https://doi.org/10.3389/fmicb.2014.00356
Glowinski F, Holland C, Thiede B, Jungblut PR, Meyer TF. Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics. Front Microbiol. 2014 Jul 18;5:356. doi: 10.3389/fmicb.2014.00356. eCollection 2014. PMID: 25101063; PMCID: PMC4102909.
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Front Microbiol. 2014 Jul 18;5:356. doi: 10.3389/fmicb.2014.00356. eCollection 2014.

Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics.

Frontiers in microbiology

Frithjof Glowinski, Carsten Holland, Bernd Thiede, Peter R Jungblut, Thomas F Meyer

Affiliations

  1. Department of Molecular Biology, Max Planck Institute for Infection Biology Berlin, Germany.
  2. The Biotechnology Centre of Oslo, University of Oslo Oslo, Norway ; Department of Biosciences, University of Oslo Oslo, Norway.

PMID: 25101063 PMCID: PMC4102909 DOI: 10.3389/fmicb.2014.00356

Abstract

Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS), which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC) of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12Δ CagA deletion mutant, and a P12Δ PAI deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr) phosphopeptides and analyzed by nano-LC-Orbitrap MS. In total, 85 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK family. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin-linked factors, whereas the T4SS primarily modulates JNK and p38 activation.

Keywords: CagA; H. pylori; SILAC; T4SS; phosphoproteomics; tyrosine signaling

References

  1. Gut. 2001 Jul;49(1):18-22 - PubMed
  2. Nat Cell Biol. 2002 Aug;4(8):565-73 - PubMed
  3. Nat Biotechnol. 2009 Jul;27(7):598-9 - PubMed
  4. Nat Biotechnol. 2008 Dec;26(12):1367-72 - PubMed
  5. J Biol Chem. 2000 Feb 4;275(5):3629-36 - PubMed
  6. Nat Biotechnol. 2005 Jan;23(1):94-101 - PubMed
  7. N Engl J Med. 2002 Oct 10;347(15):1175-86 - PubMed
  8. Eur J Cell Biol. 2011 Nov;90(11):880-90 - PubMed
  9. J Proteome Res. 2009 Sep;8(9):4333-41 - PubMed
  10. Mol Microbiol. 1998 Apr;28(1):37-53 - PubMed
  11. Cell. 2007 Dec 14;131(6):1190-203 - PubMed
  12. Nat Rev Cancer. 2002 Jan;2(1):28-37 - PubMed
  13. Nat Protoc. 2006;1(6):2650-60 - PubMed
  14. Microbes Infect. 2007 Jun;9(7):838-46 - PubMed
  15. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14640-5 - PubMed
  16. EMBO J. 2003 Feb 3;22(3):515-28 - PubMed
  17. Cell Host Microbe. 2012 Jun 14;11(6):576-86 - PubMed
  18. J Proteome Res. 2011 Apr 1;10(4):1794-805 - PubMed
  19. Proteomics. 2011 Jul;11(14):2798-811 - PubMed
  20. Nature. 2007 Oct 18;449(7164):862-6 - PubMed
  21. Trends Microbiol. 2010 Nov;18(11):479-86 - PubMed
  22. Biochim Biophys Acta. 2014 Apr;1843(4):715-24 - PubMed
  23. Mol Cell Proteomics. 2005 Dec;4(12):2010-21 - PubMed
  24. J Biol Chem. 2003 Feb 7;278(6):3664-70 - PubMed
  25. J Biol Chem. 2002 Mar 1;277(9):6775-8 - PubMed
  26. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9300-5 - PubMed
  27. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2451-6 - PubMed
  28. Science. 2002 Jan 25;295(5555):683-6 - PubMed
  29. Nat Cell Biol. 2000 Feb;2(2):62-9 - PubMed
  30. Cell Host Microbe. 2011 Jun 16;9(6):520-31 - PubMed
  31. Cell. 2007 Jun 29;129(7):1415-26 - PubMed
  32. Nat Rev Mol Cell Biol. 2008 Oct;9(10):815-20 - PubMed
  33. J Biol Chem. 2008 May 16;283(20):13952-63 - PubMed
  34. Nat Immunol. 2004 Nov;5(11):1166-74 - PubMed
  35. Mol Cell Proteomics. 2013 Feb;12(2):529-38 - PubMed
  36. Oncogene. 2008 Nov 24;27(55):7047-54 - PubMed
  37. Mol Microbiol. 2002 Feb;43(4):971-80 - PubMed
  38. Helicobacter. 2010 Jun;15(3):163-76 - PubMed
  39. Chem Cent J. 2008 Jul 18;2:16 - PubMed

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