Disease relevance of P2RY14

• GPR105 is widely expressed throughout many brain regions and peripheral tissues of human and rodents, and couples to a pertussis toxin-sensitive G protein [1].
• In conclusion, we have shown that although UDP-glucose inhibits forskolin-stimulated cAMP accumulation in human U373 MG astrocytoma cells, we did not detect P2Y14 receptor mRNA in these cells [2].
• Therefore, the primary aim of this study was to investigate the effects of uridine 5'-diphosphoglucose (UDP-glucose) on forskolin-stimulated cyclic AMP (cAMP) accumulation in two cell lines that reportedly express P2Y14 receptor mRNA, namely human neuroblastoma SH-SY5Y cells and human astrocytoma U373 MG cells [2].

High impact information on P2RY14

• Anti-GPR105 antibody selectively isolated a subset of hematopoietic cells within the fetal bone marrow, but not in the fetal liver, that was enriched for G0 cell cycle status and for in vitro stem-cell-like multipotential long-term culture capability [3].
• Human immature monocyte-derived dendritic cells express the G protein-coupled receptor GPR105 (KIAA0001, P2Y14) and increase intracellular calcium in response to its agonist, uridine diphosphoglucose [4].
• Selective antagonists for P2Y4 and P2Y14 receptors are still lacking [5].
• The 2-chloro-5-nitro pyridoxal-phosphate analogue 6-(2'-chloro-5'-nitro-azophenyl)-pyridoxal-alpha5-phosphate (MRS2211) is a selective antagonist. mRNA encoding for the human P2Y14-receptor is found in many tissues [6].
• The P2Y14 receptor of airway epithelial cells: coupling to intracellular Ca2+ and IL-8 secretion [7].

Biological context of P2RY14

• Cloning, pharmacology, and tissue distribution of G-protein-coupled receptor GPR105 (KIAA0001) rodent orthologs [8].
• Mutagenesis of the entire UDP-glucose receptor gene yielded receptors with increased activity but similar ligand specificities, while random mutagenesis of residues in the immediate vicinity of the ligand-binding pocket yielded mutants with altered ligand specificity [9].

Anatomical context of P2RY14

• To further characterise the role of GPR105, we demonstrate by immunohistochemistry with receptor-specific antiserum that GPR105 protein is widely distributed throughout the post mortem human brain where it is localised to glial cells, and specifically co-localises with astrocytes [1].
• Using quantitative RT-PCR we also show that GPR105 mRNA exhibits a restricted expression profile in an array of human cell lines and primary cells, with prominent expression detected in immune cells including neutrophils, lymphocytes, and megakaryocytic cells [1].
• Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 [10].
• P2Y14 mRNA was weakly expressed by putative microglia [11].
• Schwann cells expressed P2Y2 mRNA, and the nonneuronal cells around the DRG neurons, perhaps the satellite cells, expressed P2Y12 and P2Y14 mRNAs [11].

Associations of P2RY14 with chemical compounds

• Finally, we show that expression of GPR105 mRNA in the rat brain is up-regulated by immunologic challenge with lipopolysaccharide [1].
• To investigate the G protein selectivity of GPR105, we used chimeric Galpha subunits (Galpha(qi5), Galpha(qo5), and Galpha(qs5)) and an intracellular Ca(2+) mobilisation assay to demonstrate that GPR105 couples to Galpha subunits of the G(i/o) family but not to G(s) family proteins or to endogenous G(q/11) proteins in HEK-293 cells [1].
• It has recently been shown that UDP-glucose is a potent agonist of the orphan G-protein-coupled receptor (GPCR) KIAA0001 [8].

Other interactions of P2RY14

• KIAA0001 and D3S3882 derive from the transcript of a putative G-protein-coupled receptor gene that was excluded as a candidate by sequencing of patient DNA [12].

Analytical, diagnostic and therapeutic context of P2RY14

• By first sensitizing the P2Y14 receptor and then redirecting ligand specificity, we were able to create mutant receptors suitable for a simple biosensor [9].

References