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Published on: December 27, 2016

CagA phosphorylation-dependent MMP-9 expression in gastric epithelial cells

Young-Hee Nam1, Eunju Ryu, Doyeon Lee

  • 1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.

Helicobacter
|July 19, 2011
PubMed
Abstract

Insights

Phosphorylated CagA from Helicobacter pylori infection significantly increases matrix metalloproteinase-9 (MMP-9) secretion in gastric cells. This process involves CagA phosphorylation, SHP-2, ERK, and NF-κB pathways.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Cell Biology

Background:

  • Helicobacter pylori infection is linked to increased matrix metalloproteinases (MMPs) in gastric cells.
  • The specific role of phosphorylated CagA in inducing MMP-9, a basement membrane protease, remains unclear.

Purpose of the Study:

  • To investigate if CagA presence and its phosphorylation status influence MMP-9 expression in gastric epithelial cells.

Main Methods:

  • Analyzed MMP-9 secretion in AGS cells with CagA (with/without EPIYA motif) from H. pylori or ectopic expression.
  • Studied signaling pathways regulating CagA-dependent MMP-9 production.

Main Results:

  • Tyrosine-phosphorylated CagA (EPIYA present) induced higher MMP-9 secretion than non-phosphorylated CagA.
  • Wild-type CagA increased MMP-9 secretion more than phosphorylation-resistant CagA.
  • Inhibitors of CagA phosphorylation (PP1), SHP-2 phosphatase, ERK, and NF-κB pathways reduced MMP-9 secretion.

Conclusions:

  • CagA phosphorylation by Src family kinases, via the EPIYA motif, activates SHP-2.
  • Activated SHP-2, ERK, and CagA-dependent NF-κB signaling are crucial for MMP-9 induction.

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