Interaction between the Helicobacter pylori CagA and alpha-Pix in gastric epithelial AGS cells
Hye Yeon Baek1, Joo Weon Lim, Hyeyoung Kim
1Department of Pharmacology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
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 alpha-Pix interacts with CagA and alpha-Pix was constitutively expressed in AGS cells. Upon H. pylori stimulation, CagA was translocated into the cells and the expression of alpha-Pix (PAK-interactive exchange factor) was increased in AGS cells time dependently. The interaction of alpha-Pix with CagA was increased by H. pylori infection in AGS cells. Phosphorylation of CagA induces the dephosphorylation of alpha-Pix in AGS cells. alpha-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 alpha-Pix, which may modulate cytoskeletal changes of gastric epithelial cells through PAK.
More Related Videos
08:24Profiling Luminal pH in Three-Dimensional Gastrointestinal Organoids Using Microelectrodes
Published on: July 5, 2024
10:44One-step Negative Chromatographic Purification of Helicobacter pylori Neutrophil-activating Protein Overexpressed in Escherichia coli in Batch Mode
Published on: June 18, 2016
Related Concept Videos
Gastritis II: Pathophysiology
Peptic Ulcer
Peptic Ulcer Disease II: Pathophysiology
Pathophysiology of Peptic Ulcer Disease: Injurious Factors
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds to M3...
Mucosal Barrier of the Stomach
Within parietal cells, carbonic acid is first formed through the reaction of water and carbon dioxide. The dissociation of carbonic acid releases bicarbonate and hydrogen ions. The bicarbonate...
Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
