Abstract
p2y5 is an orphan G protein-coupled receptor that is closely related to the fourth lysophosphatidic acid (LPA) receptor, LPA4. Here we report that p2y5 is a novel LPA receptor coupling to the G13-Rho signaling pathway. "LPA receptor-null" RH7777 and B103 cells exogenously expressing p2y5 showed [3H]LPA binding, LPA-induced [35S]guanosine 5'-3-O-(thio)triphosphate binding, Rho-dependent alternation of cellular morphology, and Gs/13 chimeric protein-mediated cAMP accumulation. LPA-induced contraction of human umbilical vein endothelial cells was suppressed by small interfering RNA knockdown of endogenously expressed p2y5. We also found that 2-acyl-LPA had higher activity to p2y5 than 1-acyl-LPA. A recent study has suggested that p2y5 is an LPA receptor essential for human hair growth. We confirmed that p2y5 is a functional LPA receptor and propose to designate this receptor LPA6.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Calcium / metabolism*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Membrane / metabolism
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Cells, Cultured
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Cloning, Molecular
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Cyclic AMP / metabolism*
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism
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GTP-Binding Protein alpha Subunits, G12-G13 / genetics
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GTP-Binding Protein alpha Subunits, G12-G13 / metabolism*
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Humans
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Liver Neoplasms, Experimental / metabolism
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Liver Neoplasms, Experimental / pathology
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Lysophospholipids / metabolism*
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Radioligand Assay
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Rats
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism*
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Umbilical Veins / cytology
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Umbilical Veins / metabolism
Substances
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LPAR4 protein, human
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Lysophospholipids
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Receptors, Purinergic P2
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Guanosine 5'-O-(3-Thiotriphosphate)
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Cyclic AMP
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GTP-Binding Protein alpha Subunits, G12-G13
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lysophosphatidic acid
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Calcium