P2RY14 Membrane Protein Introduction

Introduction of P2RY14

P2RY14 is encoded by P2RY14 gene. It belongs to the G-protein-coupled receptor (GPCR) family which has been reported to regulate a panoply of cell signaling and physiologic responses. P2RY14 is one of the eight-member family of nucleotide-activated P2Y receptors and it is activated by UDP-glucose and other nucleotide sugars. It is also known as UDP glucose receptor because UDP glucose, UDP galactose, and UDP-N-acetylglucosamine are identified as potent agonists of P2RY14.

Function of P2RY14 Membrane Protein

P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides and are widely expressed and play important roles in physiology and pathophysiology. The activity of P2RY14 is mediated by its agonist, UDP-glucose. The interaction between P2RY14 and UDP-glucose can inhibit the forskolin stimulated cAMP accumulation in human U373 MG cells. P2RY14 expresses in many brain regions and peripheral tissues of human and rodents widely. P2RY14 is enriched and regulates the G0 cell cycle status in hematopoietic cells in the fetal bone marrow, but not in the fetal liver because anti-P2RY14 antibodies can be isolated from a subset of hematopoietic cells. P2RY14 expresses in the human immature monocyte-derived dendritic cells and the interaction between P2RY14 and its agonist, uridine diphosphogulcose is reported to increase intracellular calcium. At the same time, P2RY14 is expressed in leukocytes and other immune/inflammatory cells robustly and are upregulated after immunologic challenge, suggesting that the P2RY14 plays an important role in immune or inflammatory responses.

Fig.1 Signaling pathways associated with P2RY14 activation (Lazarowski and Harden, 2015).

Application of P2RY14 Membrane Protein in Literature

1. Lazarowski, E.R., et al. UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation. Mol Pharmacol. 2015, 88, 151-161. PubMed ID: 25829059
   
   

   This article reviews the P2RY14, which is a G-protein-coupled receptor targeted by UDP sugars, plays an important role in the diverse set of physiologic responses including immune and inflammatory.

2. Meister J., et al. The G Protein-coupled Receptor P2Y(14) Influences Insulin Release and Smooth Muscle Function in Mice. The Journal of Biological Chemistry. 2014, 289(34):23353-23366. PubMed ID: 24993824
   
   

   This article reports that P2RY14 is a novel modulator of insulin secretion because P2RY14 deficiency significantly changed expression of components involved in insulin secretion.

3. Azroyan A., et al. Renal Intercalated Cells Sense and Mediate Inflammation via the P2Y(14) Receptor. PLoS ONE. 2015, 10(3):e0121419. PubMed ID: 25799465
   
   

   This article shows that P2RY14 expresses in the intercalated cells and mediates the development of sterile inflammation in the kidney.

4. Kook SH., et al. The expression of P2Y14, a purinergic G-protein coupled receptor, defines functionally distinct subpopulations in placenta-derived hematopoietic stem progenitor cells. Leukemia. 2017, 31:2837. PubMed ID: 28804125
   
   

   This article focuses on the function of P2RY14 in stem progenitor cells and the results of the paper indicate that P2RY14 expression could be used as a phenotypic marker to further dissect placental HSPCs.

5. Barrett MO., et al. A Selective High-Affinity Antagonist of the P2Y(14) Receptor Inhibits UDP-Glucose–Stimulated Chemotaxis of Human Neutrophils. Mol. Pharmacol. 2013, 84(1):41-49. PubMed ID: 23592514
   
   

   The authors of the article synthesize a series of molecules, which can inhibit the P2RY14 effectively. One of these molecules, a 4,7-disubstituted 2-naphthoic acid derivative (PPTN), is a highly selective high-affinity antagonist of the P2RY14 and is useful for interrogating the action of this receptor in physiologic systems.

P2RY14 Preparation Options

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Reference

1. Lazarowski ER & Harden TK. (2015) UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y6 Receptor Activation. Mol. Pharmacol. 88(1):151.

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