The Helicobacter Pylori CagA Protein Induces Tyrosine Dephosphorylation of Ezrin

Proteomics. 2004 Oct;4(10):2961-8. doi: 10.1002/pmic.200400915.

Abstract

Helicobacter pylori is one of the most wide-spread bacterial pathogens and infects the human stomach to cause diseases, such as gastritis, gastric ulceration, and gastric cancer. A major virulence determinant is the H. pylori CagA protein (encoded by the cytotoxin-associated gene A) which is translocated from the bacteria into the cytoplasm of host cells by a type IV secretion system. In the host cell, CagA is phosphorylated on tyrosine residues and induces rearrangements of the actin cytoskeleton. We have previously shown that tyrosine-phosphorylated CagA inhibits the catalytic activity of Src family kinases and induces tyrosine dephosphorylation of several host cell proteins. Here, we identified one of these proteins as ezrin by a combination of preparative gel electrophoresis, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). Specific pharmacological inhibition of Src family kinases also induces ezrin dephosphorylation. Therefore, ezrin dephosphorylation appears to be induced by CagA-mediated Src inactivation. Ezrin is the founding member of the ezrin-radixin-moesin (ERM) family of proteins which are signalling integrators at the cell cortex. Since ezrin is a component of microvilli and a linker protein between actin filaments and membrane proteins, this observation has important implications for H. pylori pathogenesis and might also help to explain the development of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antigens, Bacterial / chemistry*
  • Bacterial Proteins / chemistry*
  • Cytoskeletal Proteins
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Helicobacter pylori / metabolism*
  • Humans
  • Phosphoproteins / chemistry*
  • Phosphorylation
  • Proteome
  • RNA Interference
  • Signal Transduction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Stomach Neoplasms / microbiology
  • Trichloroacetic Acid / pharmacology
  • Tyrosine / chemistry*
  • src-Family Kinases / metabolism

Substances

  • Actins
  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Proteome
  • cagA protein, Helicobacter pylori
  • ezrin
  • Tyrosine
  • Trichloroacetic Acid
  • src-Family Kinases