ArticleAmerican journal of physiology. Cell physiology2012
The UDP-sugar-sensing P2Y(14) receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Urinary UDP-sugars provide actionable prediction of acute kidney injury in cardiac surgery patients.American journal of physiology. Heart and circulatory physiology · 2026Article
- UDP-Glucose-P2Y14 Receptor Signaling Enhances the Responsiveness of Hematopoietic Stem/Progenitor Cells to Chemoattractants by Facilitating Membrane Lipid Raft Formation and Nlrp3 Inflammasome Activation.Stem cell reviews and reports · 2026Article
- P2Y14 receptor activation and neutrophil signaling: linking inflammation to systemic pathophysiology.Purinergic signalling · 2026Review
- Preoperative donor urinary UDP-Glc as an independent risk factor for delayed graft function.Frontiers in immunology · 2025Observational
- Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy.Circulation research · 2024Article
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- Exploring bias in platelet P2YBritish journal of pharmacology · 2024Review
- Article
- ATP functions as a primary alarmin in allergen-induced type 2 immunity.American journal of physiology. Cell physiology · 2023Review
- Uridine Diphosphate Glucose (UDP-G) Activates Oxidative Stress and Respiratory Burst in Isolated Neutrophils.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- The purinergic P2Y14 receptor links hepatocyte death to hepatic stellate cell activation and fibrogenesis in the liver.Science translational medicine · 2022Article
- Purinergic receptors in airway hydration.Biochemical pharmacology · 2021Review
- P2Y14 Receptor as a Target for Neutrophilia Attenuation in Severe COVID-19 Cases: From Hematopoietic Stem Cell Recruitment and Chemotaxis to Thrombo-inflammation.Stem cell reviews and reports · 2021Review
- Exploration of Alternative Scaffolds for P2YJournal of medicinal chemistry · 2020Article
- Proinflammatory P2Y14 receptor inhibition protects against ischemic acute kidney injury in mice.The Journal of clinical investigation · 2020Article
- Methotrexate-loaded tumour-cell-derived microvesicles can relieve biliary obstruction in patients with extrahepatic cholangiocarcinoma.Nature biomedical engineering · 2020Article
- P2YACS medicinal chemistry letters · 2020Article
- Role of UDP-Sugar Receptor P2YInternational journal of molecular sciences · 2020Article
- Structure-Guided Modification of Heterocyclic Antagonists of the P2YJournal of medicinal chemistry · 2018Article
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Funding
Abstract
The G(i)-coupled P2Y(14) receptor (P2Y(14)-R) is potently activated by UDP-sugars and UDP. Although P2Y(14)-R mRNA is prominently expressed in circulating neutrophils, the signaling pathways and functional responses associated with this receptor are undefined. In this study, we illustrate that incubation of isolated human neutrophils with UDP-glucose resulted in cytoskeleton rearrangement, change of cell shape, and enhanced cell migration. We also demonstrate that UDP-glucose promotes rapid, robust, and concentration-dependent activation of RhoA in these cells. Ecto-nucleotidases expressed on neutrophils rapidly hydrolyzed extracellular ATP, but incubation with UDP-glucose for up to 1 h resulted in negligible metabolism of the nucleotide-sugar. HL60 human promyelocytic leukemia cells do not express the P2Y(14)-R, but neutrophil differentiation of HL60 cells with DMSO resulted in markedly enhanced P2Y(14)-R expression. Accordingly, UDP-glucose, UDP-galactose, and UDP-N-acetylglucosamine promoted Rho activation in differentiated but not in undifferentiated HL60 cells. Stable expression of recombinant human P2Y(14)-R conferred UDP-sugar-promoted responses to undifferentiated HL60 cells. UDP-glucose-promoted RhoA activation also was accompanied by enhanced cell migration in differentiated HL60 cells, and these responses were blocked by Rho kinase inhibitors. These results support the notion that UDP-glucose is a stable and potent proinflammatory mediator that promotes P2Y(14)-R-mediated neutrophil motility via Rho/Rho kinase activation.
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