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Gene Review

P2ry13  -  purinergic receptor P2Y, G-protein coupled 13

Mus musculus

Synonyms: 2010001L06Rik, G-protein coupled receptor 86, GPCR1, GPR94, Gpr86, ...
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Disease relevance of P2ry13

  • Here we show that the KSHV GPCR enhances the expression of VEGF by stimulating the activity of the transcription factor hypoxia-inducible factor (HIF)-1alpha, which activates transcription from a hypoxia response element within the 5'-flanking region of the VEGF promoter [1].

High impact information on P2ry13

  • GPCR-dependent ROS formation is absent in lipopolysaccharide (LPS)-primed P-Rex1(-/-) neutrophils, but less affected in unprimed or TNFalpha-primed cells [2].
  • In order to investigate the dynamic mechanisms associated with GPCR signaling, the intracellular translocation of a green fluorescent protein-tagged PKD was analyzed by real-time visualization in fibroblasts and epithelial cells stimulated with bombesin, a GPCR agonist [3].
  • Protein kinase D (PKD)/protein kinase C (PKC) mu is a serine/threonine protein kinase that can be activated by physiological stimuli like growth factors, antigen-receptor engagement and G protein-coupled receptor (GPCR) agonists via a phosphorylation-dependent mechanism that requires PKC activity [3].
  • Vasoconstriction elicited by angiotensin II (Ang II) or phenylephrine (PE), G-protein-coupled receptor (GPCR) agonists, but not that elicited by arachidonic acid or KCl, was greater in eNOS KO mice [4].
  • These data show for the first time the role of G protein receptor phosphorylation and internalization per se in the regulatory function of an endocrine system controlled by a GPCR [5].

Biological context of P2ry13

  • The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis [6].
  • Here, the ligand binding, activation, and tissue distribution of the orphan G protein-coupled receptor (GPCR) GPR92 were studied [7].
  • The GPCR-activated PI3Kgamma is weakly expressed in the heart, but the deletion of its expression in mice causes remarkable phenotypes [8].
  • ProHB-EGF is bound to the cell membrane and released after cleavage by metalloproteinases; its action may contribute to effects of GPCR agonists on cell growth [9].
  • This functional cascade requires modulation of agonist-induced calcium transient by EGFR and PI3K with extremely fast kinetics, suggesting a novel paradigm for GPCR-mediated calcium signaling, which may offer future therapeutic targets [9].

Anatomical context of P2ry13

  • We have identified an orphan G protein-coupled receptor, SP174, that shares a high degree of homology with the recently described ADP receptor P2Y(12). mRNA for SP174 is abundant in the brain and in cells of the immune system [10].
  • Rac2-deficient neutrophils cannot chemotax, produce ROS, or degranulate upon G protein-coupled receptor (GPCR) activation [2].
  • Using both a pharmacological approach and small interference RNA, we identified P2Y13 as the main partner in hepatic HDL endocytosis, in cultured cells as well as in situ in perfused mouse livers [6].
  • Only P2Y1 and P2Y13 are present on the membrane of hepatocytes [6].
  • It is the most abundant GPCR activated by LPA found in the small intestinal intraepithelial CD8+ cytotoxic T cells [7].

Associations of P2ry13 with chemical compounds

  • ADP potently stimulates SP174 with an EC(50) of 60 nM, and other related nucleotides are active as well, with a rank order of potency 2-methylthio-ADP tetrasodium = adenosine 5'-O-2-(thio)diphosphate = 2-methylthio-ATP tetrasodium > ADP > AP3A >ATP > IDP [10].
  • We also found a new important action of the antithrombotic agent AR-C69931MX as a strong activator of P2Y13-mediated HDL endocytosis [6].


  1. The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha. Sodhi, A., Montaner, S., Patel, V., Zohar, M., Bais, C., Mesri, E.A., Gutkind, J.S. Cancer Res. (2000) [Pubmed]
  2. P-Rex1 regulates neutrophil function. Welch, H.C., Condliffe, A.M., Milne, L.J., Ferguson, G.J., Hill, K., Webb, L.M., Okkenhaug, K., Coadwell, W.J., Andrews, S.R., Thelen, M., Jones, G.E., Hawkins, P.T., Stephens, L.R. Curr. Biol. (2005) [Pubmed]
  3. Rapid protein kinase D translocation in response to G protein-coupled receptor activation. Dependence on protein kinase C. Rey, O., Young, S.H., Cantrell, D., Rozengurt, E. J. Biol. Chem. (2001) [Pubmed]
  4. The role of the RhoA/Rho-kinase signaling pathway in renal vascular reactivity in endothelial nitric oxide synthase null mice. Williams, J., Bogwu, J., Oyekan, A. J. Hypertens. (2006) [Pubmed]
  5. Impact of Impaired Receptor Internalization on Calcium Homeostasis in Knock-In Mice Expressing a Phosphorylation-Deficient Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor. Bounoutas, G.S., Tawfeek, H., Fröhlich, L.F., Chung, U.I., Abou-Samra, A.B. Endocrinology (2006) [Pubmed]
  6. The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis. Jacquet, S., Malaval, C., Martinez, L.O., Sak, K., Rolland, C., Perez, C., Nauze, M., Champagne, E., Tercé, F., Gachet, C., Perret, B., Collet, X., Boeynaems, J.M., Barbaras, R. Cell. Mol. Life Sci. (2005) [Pubmed]
  7. Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. Kotarsky, K., Boketoft, A., Bristulf, J., Nilsson, N.E., Norberg, A., Hansson, S., Owman, C., Sillard, R., Leeb-Lundberg, L.M., Olde, B. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  8. Phosphoinositide 3-kinase gamma: kinase-dependent and -independent activities in cardiovascular function and disease. Alloatti, G., Montrucchio, G., Lembo, G., Hirsch, E. Biochem. Soc. Trans. (2004) [Pubmed]
  9. Heparin binding EGF is necessary for vasospastic response to endothelin. Chansel, D., Ciroldi, M., Vandermeersch, S., Jackson, L.F., Gomez, A.M., Henrion, D., Lee, D.C., Coffman, T.M., Richard, S., Dussaule, J.C., Tharaux, P.L. FASEB J. (2006) [Pubmed]
  10. P2Y(13): identification and characterization of a novel Galphai-coupled ADP receptor from human and mouse. Zhang, F.L., Luo, L., Gustafson, E., Palmer, K., Qiao, X., Fan, X., Yang, S., Laz, T.M., Bayne, M., Monsma, F. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
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