Interaction between the Helicobacter pylori CagA and α-pix in gastric epithelial AGS cells

Yeon Baek Hye, Weon Lim Joo, Hyeyoung Kim

Research output: Chapter in Book/Report/Conference proceedingConference contribution

23 Citations (Scopus)

Abstract

The gastric pathogen Helicobacter pylori (H. pylori) translocates the CagA protein into epithelial cells by a type IV secretion process. Upon translocation into the host cell cytosol, CagA undergoes tyrosine phosphorylation. Phosphorylation of CagA occurs within the C terminus of the protein and is mediated by members of the Src family of tyrosine kinases. Phosphorylation of CagA induces the dephosphorylation of as yet unidentified cellular proteins, rearrangements of the host cell actin cytoskeleton, and cell scattering. This article aims to determine the cellular protein that interacts with CagA. Gastric epithelial AGS cells were stimulated with CagA-positive H. pylori (NCTC11637, at a bacteria/cell ratio of 500:1) and cultured in antibiotic-free medium. Proteins were isolated from the cells with or without H. pylori infection. CagA-interactive protein was determined by immunoprecipitation using anti-CagA antibody and proteomic analysis. We found that α-Pix interacts with CagA and α-Pix was constitutively expressed in AGS cells. Upon H. pylori stimulation, CagA was translocated into the cells and the expression of α-Pix (PAK-interactive exchange factor) was increased in AGS cells time dependently. The interaction of α-Pix with CagA was increased by H. pylori infection in AGS cells. Phosphorylation of CagA induces the dephosphorylation of α-Pix in AGS cells. α-Pix is a family of PAK-binding proteins that strongly activates PAK (p21-activated tyrosine kinase). PAK regulates changes in gene expression and mediates actin cytoskeletal and cell morphological changes. The novel finding of this study is that phosphorylation of CagA induces the dephosphorylation of α-Pix, which may modulate cytoskeletal changes of gastric epithelial cells through PAK.

Original languageEnglish
Title of host publicationSignal Transduction Pathways, Part D
Subtitle of host publicationInflammatory Signaling Pathways and Neuropathology
PublisherBlackwell Publishing Inc.
Pages18-23
Number of pages6
ISBN (Print)1573316970, 9781573316972
DOIs
Publication statusPublished - 2007 Jan

Publication series

NameAnnals of the New York Academy of Sciences
Volume1096
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Hye, Y. B., Joo, W. L., & Kim, H. (2007). Interaction between the Helicobacter pylori CagA and α-pix in gastric epithelial AGS cells. In Signal Transduction Pathways, Part D: Inflammatory Signaling Pathways and Neuropathology (pp. 18-23). (Annals of the New York Academy of Sciences; Vol. 1096). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1397.065