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].

References