ArticleThe Journal of clinical investigation2012
c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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145 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis.BMC infectious diseases · 2012Pooled it
- Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans.The Journal of clinical investigation · 2013Trial
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- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Helicobacter pylori-induced PPFIA4 orchestrates immune network-promoting gastritis and gastric bacterial colonization.The Journal of clinical investigation · 2026Article
- Managing dangerous liaisons: lessons fromJournal of bacteriology · 2026Review
- Bacterial EPIYA/EPIYA-like effector motifs and host regulatory pY-SH2 logic: a sequence-informed three-layer convergence model.Frontiers in cellular and infection microbiology · 2026Article
- Enhanced ADP-heptose-dependent NF-κB activation bymicroLife · 2026Article
- Pathogenicity and virulence ofVirulence · 2025Review
- Infection and herbicide exposure implicate c-Abl kinase in α-Synuclein Ser129 phosphorylation.Cell communication and signaling : CCS · 2025Article
- A single amino acid in the Salmonella effector SarA/SteE triggers supraphysiological activation of STAT3 for anti-inflammatory gene expression.Cell reports · 2025Article
- Effect ofImmunotherapy · 2025Review
- Environmental factors in gastric carcinogenesis and preventive intervention strategies.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Review
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- Cultivation and molecular characterization of viable Helicobacter pylori from the root canal of 170 deciduous teeth of children.Cell communication and signaling : CCS · 2024Article
- The two coin sides of bacterial extracellular membrane nanovesicles: atherosclerosis trigger or remedy.Discover nano · 2024Review
- More powerful dysregulation of Helicobacter pylori East Asian-type CagA on intracellular signalings.BMC microbiology · 2024Article
- Helicobacter pylori and Epstein-Barr virus infection in cell polarity alterations.Folia microbiologica · 2024Review
85 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
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Abstract
Many bacterial pathogens inject into host cells effector proteins that are substrates for host tyrosine kinases such as Src and Abl family kinases. Phosphorylated effectors eventually subvert host cell signaling, aiding disease development. In the case of the gastric pathogen Helicobacter pylori, which is a major risk factor for the development of gastric cancer, the only known effector protein injected into host cells is the oncoprotein CagA. Here, we followed the hierarchic tyrosine phosphorylation of H. pylori CagA as a model system to study early effector phosphorylation processes. Translocated CagA is phosphorylated on Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs EPIYA-A, EPIYA-B, and EPIYA-C in Western strains of H. pylori and EPIYA-A, EPIYA-B, and EPIYA-D in East Asian strains. We found that c-Src only phosphorylated EPIYA-C and EPIYA-D, whereas c-Abl phosphorylated EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D. Further analysis revealed that CagA molecules were phosphorylated on 1 or 2 EPIYA motifs, but never simultaneously on 3 motifs. Furthermore, none of the phosphorylated EPIYA motifs alone was sufficient for inducing AGS cell scattering and elongation. The preferred combination of phosphorylated EPIYA motifs in Western strains was EPIYA-A and EPIYA-C, either across 2 CagA molecules or simultaneously on 1. Our study thus identifies a tightly regulated hierarchic phosphorylation model for CagA starting at EPIYA-C/D, followed by phosphorylation of EPIYA-A or EPIYA-B. These results provide insight for clinical H. pylori typing and clarify the role of phosphorylated bacterial effector proteins in pathogenesis.
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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.