ArticleThe Journal of biological chemistry2011
Potentiation of Helicobacter pylori CagA protein virulence through homodimerization.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- Kinase Activity of PAR1b, Which Mediates Nuclear Translocation of the BRCA1 Tumor Suppressor, Is Potentiated by Nucleic Acid-Mediated PAR1b Multimerization.International journal of molecular sciences · 2022Article
- Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Structure of cytotoxic associated antigen A protein ofVeterinary world · 2020Article
- Molecular anatomy and pathogenic actions of Helicobacter pylori CagA that underpin gastric carcinogenesis.Cellular & molecular immunology · 2020Review
- Inhibition of polarity-regulating kinase PAR1b contributes to Helicobacter pylori inflicted DNA Double Strand Breaks in gastric cells.Cell cycle (Georgetown, Tex.) · 2019Article
- Evaluating the origin and virulence of a Helicobacter pylori cagA-positive strain isolated from a non-human primate.Scientific reports · 2018Article
- Structure and function of Helicobacter pylori CagA, the first-identified bacterial protein involved in human cancer.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2017Review
- Impact of structural polymorphism for the Helicobacter pylori CagA oncoprotein on binding to polarity-regulating kinase PAR1b.Scientific reports · 2016Article
- Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus.Nature microbiology · 2016Article
- Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA.Scientific reports · 2016Article
- Dramatic increase in SHP2 binding activity of Helicobacter pylori Western CagA by EPIYA-C duplication: its implications in gastric carcinogenesis.Scientific reports · 2015Article
- A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions.PLoS pathogens · 2015Article
- Natural variant of the Helicobacter pylori CagA oncoprotein that lost the ability to interact with PAR1.Cancer science · 2014Article
- Article
- Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains.The Journal of clinical investigation · 2012Article
- TheGut microbesReview
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic infection with Helicobacter pylori cagA-positive strains is associated with atrophic gastritis, peptic ulceration, and gastric carcinoma. The cagA gene product, CagA, is delivered into gastric epithelial cells via type IV secretion, where it undergoes tyrosine phosphorylation at the EPIYA motifs. Tyrosine-phosphorylated CagA binds and aberrantly activates the oncogenic tyrosine phosphatase SHP2, which mediates induction of elongated cell morphology (hummingbird phenotype) that reflects CagA virulence. CagA also binds and inhibits the polarity-regulating kinase partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) via the CagA multimerization (CM) sequence independently of tyrosine phosphorylation. Because PAR1 exists as a homodimer, two CagA proteins appear to be passively dimerized through complex formation with a PAR1 dimer in cells. Interestingly, a CagA mutant that lacks the CM sequence displays a reduced SHP2 binding activity and exhibits an attenuated ability to induce the hummingbird phenotype, indicating that the CagA-PAR1 interaction also influences the morphological transformation. Here we investigated the role of CagA dimerization in induction of the hummingbird phenotype with the use of a chemical dimerizer, coumermycin. We found that CagA dimerization markedly stabilizes the CagA-SHP2 complex and thereby potentiates SHP2 deregulation, causing an increase in the number of hummingbird cells. Protrusions of hummingbird cells induced by chemical dimerization of CagA are further elongated by simultaneous inhibition of PAR1. This study revealed a role of the CM sequence in amplifying the magnitude of SHP2 deregulation by CagA, which, in conjunction with the CM sequence-mediated inhibition of PAR1, evokes morphological transformation that reflects in vivo CagA virulence.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.