The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor.
In CHO cells stably expressing the GPR87 fused with a G16alpha protein, lysophosphatidic acid (LPA) evoked an intracellular Ca(2+) increase in a high affinity manner. The Ca(2+) increase was reversibly blocked by the LPA receptor antagonists and inhibited by pretreatment of the cells with GPR87-specific siRNAs. GPR87 was shown to be closer to the P2Y and P2Y-related receptors than LPA receptors by ClustalW analyses. However, none of nucleotides and their derivatives activated GPR87. The human gpr87 is located on the chromosome 3q25 in a cluster containing p2y12,13,14. RT-PCR analysis showed that the mouse GPR87 was expressed in placenta, ovary, testis, prostate, brain, and skeletal muscle. The 3D model of GPR87-LPA complex indicated that the ligand interacted with R115 and K296 of GPR87, which are well conserved in the P2Y receptors. These results suggest that the GPR87 is a LPA receptor which evolved from a common ancestor of P2Y receptors.
Tabata
Ken-ichi
K
Laboratory of Pharmcoinformatics, Department of Bioscience and Bioinformatics, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
Baba
Kiyoshi
K
Shiraishi
Akira
A
Ito
Masahiro
M
Fujita
Norihisa
N
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D011422:Propionates / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014544:Uridine Triphosphate / Q000494:pharmacology
C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; C526276:GPR87 protein, human; C526277:GPR87 protein, mouse; D044385:GTP-Binding Protein alpha Subunits; D007555:Isoxazoles; D008246:Lysophospholipids; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D011993:Recombinant Fusion Proteins; C032881:lysophosphatidic acid; D002118:Calcium; D014544:Uridine Triphosphate