Identification of cDNAs encoding two G protein-coupled receptors for lysosphingolipids.
The structural similarity of lysosphingolipids to lysophosphatidic acid (LPA) prompted a sequence-based search for lysosphingolipid receptors using cDNA sequence of the Edg2 human LPA receptor. Two closely related G protein-coupled receptors, rat H218 and human Edg3, are highly similar to Edg2. When overexpressed in Jurkat cells, H218 and Edg3 activated serum response element-driven transcriptional reporter gene in response to sphingosine 1-phosphate (S1P), dihydro-S1P and sphingosylphosphorylcholine, but not to LPA. H218 and Edg3 expressed in Xenopus oocytes conferred responsiveness to S1P and dihydro-S1P in agonist-triggered 45Ca2+ efflux. Therefore, H218 and Edg3 are functional receptors for S1P and perhaps other closely related lysosphingolipids.
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Department of Medicine, University of California, San Francisco 94143, USA. songzhu@itsa.ucsf.edu
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Coughlin
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013107:Sphingolipids / Q000378:metabolism* / Q000494:pharmacology; D014981:Xenopus
D017931:DNA Primers; D018076:DNA, Complementary; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D011993:Recombinant Fusion Proteins; D013107:Sphingolipids; D008156:Luciferases; D019204:GTP-Binding Proteins