Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Cloning, Molecular
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DNA Primers
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DNA, Complementary
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GTP-Binding Proteins / metabolism
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Humans
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Jurkat Cells
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Luciferases / biosynthesis
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Molecular Sequence Data
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Oocytes / drug effects
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Oocytes / physiology
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Polymerase Chain Reaction
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Rats
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Receptors, Cell Surface / biosynthesis*
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / physiology
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Receptors, G-Protein-Coupled*
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Receptors, Lysophosphatidic Acid
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Receptors, Lysophospholipid
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / chemistry
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Sequence Alignment
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Sequence Homology, Amino Acid
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Sphingolipids / metabolism*
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Sphingolipids / pharmacology
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Xenopus
Substances
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DNA Primers
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DNA, Complementary
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, Lysophosphatidic Acid
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Receptors, Lysophospholipid
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Recombinant Fusion Proteins
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Sphingolipids
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Luciferases
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GTP-Binding Proteins
Associated data
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GENBANK/AF022137
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GENBANK/AF022138
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GENBANK/AF022139