Abstract |
Infection with Helicobacter pylori induces various gastric diseases, including ulceration, gastritis and neoplasia. As H. pylori-induced cellular mechanisms leading to these disease states are widely unclear, we analysed the phosphoproteome of H. pylori-infected gastric epithelial cells. Phosphoproteins from infected cells were enriched using affinity columns and analysed by two-dimensional gel electrophoresis and mass spectrometry. Eleven novel phosphoproteins that showed differentially regulated phosphorylation levels during H. pylori infection were identified. Interestingly, the identified proteins were actin-binding, transport and folding, RNA/ DNA-binding or cancer-associated proteins. We analysed functions of one identified H. pylori-regulated candidate, the vasodilator-stimulated phosphoprotein (VASP). H. pylori induced VASP phosphorylation at residues Ser157, Ser239 and Thr278, which was enhanced by the bacterial oncogene cytotoxin-associated gene A. Overexpression of a phosphorylation-resistant VASP mutant efficiently blocked host cell elongation. We identified cGMP-dependent protein kinase G-mediated Ser239 and Thr278 phosphorylation of VASP as a crucial event in H. pylori-dependent host cell elongation. These results suggest that phosphorylated VASP could be a novel target candidate for therapeutic intervention in H. pylori-related gastric diseases.
|
Authors | Olivia Knauer, Nadine A Binai, Gert Carra, Tobias Beckhaus, Kay-Martin Hanschmann, Thomas Renné, Steffen Backert, Michael Karas, Silja Wessler |
Journal | Cellular microbiology
(Cell Microbiol)
Vol. 10
Issue 11
Pg. 2285-96
(Nov 2008)
ISSN: 1462-5822 [Electronic] India |
PMID | 18637808
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antigens, Bacterial
- Bacterial Proteins
- Cell Adhesion Molecules
- Microfilament Proteins
- Phosphoproteins
- Recombinant Fusion Proteins
- cagA protein, Helicobacter pylori
- vasodilator-stimulated phosphoprotein
- Cyclic GMP-Dependent Protein Kinases
|
Topics |
- Animals
- Antigens, Bacterial
(genetics, metabolism)
- Bacterial Proteins
(genetics, metabolism)
- Cell Adhesion Molecules
(genetics, metabolism)
- Cell Line
- Cyclic GMP-Dependent Protein Kinases
(metabolism)
- Cytoskeleton
(metabolism)
- Epithelial Cells
(cytology, metabolism, microbiology)
- Gastric Mucosa
(cytology, metabolism, microbiology)
- Helicobacter Infections
(metabolism)
- Helicobacter pylori
(metabolism)
- Humans
- Microfilament Proteins
(genetics, metabolism)
- Phosphoproteins
(genetics, metabolism)
- Recombinant Fusion Proteins
(genetics, metabolism)
- Signal Transduction
(physiology)
|