Related Experiment Video
Updated: May 31, 2026
09:18
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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
Summary
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.
Related Concept Videos
01:26Gastritis II: Pathophysiology
The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly via the oral-oral route through saliva or shared utensils, and can also be transmitted in overcrowded or unhygienic environments through contaminated water, despite its brief survival outside the body.ColonizationOnce ingested, H. pylori enters the stomach and begins colonization by navigating through the mucus layer lining the stomach wall. It...
01:25Mucosal Barrier of the Stomach
The gastric glands contain parietal cells that secrete hydrochloric acid (HCl) for digestion. The cells secrete HCl because it is highly corrosive and essential for breaking down food. To achieve this, they secrete hydrogen and chloride ions into the lumen of the gastric glands, which combine to form HCl.
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...
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...
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
01:24Peptic Ulcer Disease II: Pathophysiology
Peptic ulcer disease develops when protective mechanisms of the gastrointestinal mucosa are overwhelmed by harmful factors, leading to localized erosions in the stomach or proximal duodenum. The main causes are Helicobacter pylori infection and chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).Helicobacter pylori–Induced InjuryBacterial Adaptation and Colonization:H. pylori is a spiral, Gram-negative bacterium adapted to the acidic stomach. and transmitted through oral-oral or...
01:22Pathophysiology of Peptic Ulcer Disease: Injurious Factors
Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
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...
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...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...