Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1.
Sphingosylphosphorylcholine (SPC) is a bioactive lipid that acts as an intracellular and extracellular signalling molecule in numerous biological processes. Many of the cellular actions of SPC are believed to be mediated by the activation of unidentified G-protein-coupled receptors. Here we show that SPC is a high-affinity ligand for an orphan receptor, ovarian cancer G-protein-coupled receptor 1 (OGR1). In OGR1-transfected cells, SPC binds to OGR1 with high affinity (Kd = 33.3 nM) and high specificity and transiently increases intracellular calcium. The specific binding of SPC to OGR1 also activates p42/44 mitogen-activated protein kinases (MAP kinases) and inhibits cell proliferation. In addition, SPC causes internalization of OGR1 in a structurally specific manner.
Xu
Y
Y
Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195, USA. xuy@ccf.org
Zhu
K
K
Hong
G
G
Wu
W
W
Baudhuin
L M
LM
Xiao
Y
Y
Damron
D S
DS
D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008164:Luminescent Proteins / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
C486281:GPR68 protein, human; D007202:Indicators and Reagents; D008024:Ligands; D008164:Luminescent Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D049452:Green Fluorescent Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine; D002118:Calcium