Topics

Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells.

08:00 EDT 20th March 2020 | BioPortfolio

Summary of "Helicobacter pylori CagA oncoprotein interacts with SHIP2 to increase its delivery into gastric epithelial cells."

Chronic infection with Helicobacter pylori cagA-positive strains is causally associated with the development of gastric diseases, most notably gastric cancer. The cagA-encoded CagA protein, which is injected into gastric epithelial cells via bacterial type IV secretion, undergoes tyrosine phosphorylation at the EPIYA segments (EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D), which are present in various numbers and combinations in its C-terminal polymorphic region, thereby enabling CagA to promiscuously interact with SH2 domain-containing host cell proteins, including the prooncogenic phosphatase SHP2. Perturbation of host protein functions by aberrant complex formation with CagA has been considered to contribute to the development of gastric cancer. Here we show that SHIP2, an SH2 domain-containing phosphatidylinositol 5'-phosphatase, is a hitherto undiscovered CagA-binding host protein. Similar to SHP2, SHIP2 binds to the Western CagA-specific EPIYA-C segment or East Asian CagA-specific EPIYA-D segment via the SH2 domain in a tyrosine phosphorylation-dependent manner. In contrast to the case of SHP2, however, SHIP2 binds more strongly to EPIYA-C than to EPIYA-D. Interaction with CagA tethers SHIP2 to the plasma membrane, where it mediates production of phosphatidylinositol 3,4-diphosphate [PI(3,4)P ]. The CagA-SHIP2 interaction also potentiates the morphogenetic activity of CagA, which is caused by CagA-deregulated SHP2. This study indicates that initially delivered CagA interacts with SHIP2 and thereby strengthens H. pylori-host cell attachment by altering membrane phosphatidylinositol compositions, which potentiates subsequent delivery of CagA that binds to and thereby deregulates the prooncogenic phosphatase SHP2.

Affiliation

Journal Details

This article was published in the following journal.

Name: Cancer science
ISSN: 1349-7006
Pages:

Links

DeepDyve research library

PubMed Articles [772 Associated PubMed Articles listed on BioPortfolio]

Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis.

Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer. The cagA gene product, CagA, is delivered into gastric epithelial cells via the bacter...

Helicobacter pylori inhibits GKN1 expression via the CagA/p-ERK/AUF1 pathway.

Recent studies have shown that gastrokine 1 (GKN1), an important tumor suppressor gene, is downregulated in Helicobacter pylori (H. pylori) infected gastric mucosa and gastric cancer. However, the und...

Unique constellations of five polymorphic sites of Helicobacter pylori vacA and cagA status associated with risk of gastric cancer.

Helicobacter pylori possesses virulence genes that are involved in the pathogenesis of the bacterium. There are little data regarding all constellations of five polymorphic sites of H. pylori vacA and...

PTEN Loss and Cyclin A2 Upregulation Define a PI3K/AKT Pathway Activation in Helicobacter pylori-induced MALT and DLBCL Gastric Lymphoma With Features of MALT.

Helicobacter pylori infection is strongly associated with primary gastric diseases, such as extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma (DLBCL) with his...

cagA gene EPIYA motif genetic characterization from Colombian Helicobacter pylori isolates: Standardization of a molecular test for rapid clinical laboratory detection.

The aim of this work was to determine current cagA gene EPIYA motifs present in Colombian Helicobacter pylori isolates using a fast and reliable molecular test. DNA from eighty-five Helicobacter pylor...

Clinical Trials [374 Associated Clinical Trials listed on BioPortfolio]

The Situation of Re-infection of Helicobacter Pylori After Successful Eradication

The patients who accept the quadruple eradication program of the helicobacter pylori and success to eradicate helicobacter pylori will be followed-up to observe the situation of re-infecti...

Trial of Three Antibiotic Regimens to Eradicate Helicobacter Pylori (H. Pylori)

The purpose of this study is to compare the effectiveness of three different antibiotic regimens against Helicobacter pylori (H. pylori).

The Study of the Antimicrobial Resistance of Helicobacter Pylori in Shandong Province

The antimicrobial resistance of helicobacter pylori in Shandong province was analyzed by helicobacter pylori antibiotic sensitivity test.And the map of antimicrobial resistance of helicoba...

Safety and Immunogenicity of Chiron's Investigational H. Pylori Vaccine in Healthy Adults

This study was designed to investigate the safety and immunogenicity of Chiron's investigational H. pylori (HP3) vaccine

A Unique Regimen for Treatment of Helicobacter Pylori Infection

The triple treatment including Proton pump inhibitor (PPI) -clarithromycin and amoxicillin or metronidazole was proposed 30 years ago at the first Maastricht conference to treat helicobact...

Medical and Biotech [MESH] Definitions

A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus CAMPYLOBACTER, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus HELICOBACTER. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405).

Infections with organisms of the genus HELICOBACTER, particularly, in humans, HELICOBACTER PYLORI. The clinical manifestations are focused in the stomach, usually the gastric mucosa and antrum, and the upper duodenum. This infection plays a major role in the pathogenesis of type B gastritis and peptic ulcer disease.

A species of gram-negative, spiral-shaped bacteria found in the gastric mucosa that is associated with chronic antral gastritis. This bacterium was first discovered in samples removed at endoscopy from patients investigated for HELICOBACTER PYLORI colonization.

Ulceration of the GASTRIC MUCOSA due to contact with GASTRIC JUICE. It is often associated with HELICOBACTER PYLORI infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).

Ulcer that occurs in the regions of the GASTROINTESTINAL TRACT which come into contact with GASTRIC JUICE containing PEPSIN and GASTRIC ACID. It occurs when there are defects in the MUCOSA barrier. The common forms of peptic ulcers are associated with HELICOBACTER PYLORI and the consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).

Quick Search


DeepDyve research library

Relevant Topics

Peptic Ulcer Disease
Peptic Ulcer Disease - stomach ulcer, duodenal ulcers used to refer to all types of peptic ulcers. A peptic ulcer is an erosion in a segment of the Gastrointestinal (GI) muscularis mucosae, typically in the stomach (gastric ulcer) or the first few cent...

Infectious-diseases
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...


Searches Linking to this Article