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Comparative analysis of three murine g-protein coupled receptors activated by sphingosine-1-phosphate

Academic Article
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Overview

authors

  • Zhang, G. F.
  • Contos, J. J. A.
  • Weiner, J. A.
  • Fukushima, N.
  • Chun, Jerold

publication date

  • February 1999

journal

  • Gene  Journal

abstract

  • The cloning and analysis of the first identified lysophosphatidic acid (LPA) receptor gene, lpA1 (also referred to as vzg-1 or edg-2), led us to identify homologous murine genes that might also encode receptors for related lysophospholipid ligands. Three murine genomic clones (designated lpB1, lpB2, and lpB3) were isolated, corresponding to human/rat Edg-1, rat H218/AGR16, and human edg-3, respectively. Based on the amino acid similarities of their predicted proteins (44-52% identical), the three lpB genes could be grouped into a separate G-protein coupled receptor subfamily, distinct from that containing the LPA receptor genes lpA1 and lpA2. Unlike lpA1 and lpA2, which contain multiple coding exons, all lpB members contained a single coding exon. Heterologous expression of individual lpB members in a hepatoma cell line (RH7777), followed by 35S-GTPgammaS incorporation assays demonstrated that each of the three LPB receptors conferred sphingosine-1-phosphate-dependent, but not lysophosphatidic acid-dependent, G-protein activation. Northern blot and in situ hybridization analyses revealed overlapping as well as distinct expression patterns in both embryonic and adult tissues. This comparative characterization of multiple sphingosine-1-phosphate receptor genes and their spatiotemporal expression patterns will aid in understanding the biological roles of this enlarging lysophospholipid receptor family.

subject areas

  • Amino Acid Sequence
  • Animals
  • Gene Expression Regulation
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Humans
  • In Situ Hybridization
  • Lysophospholipids
  • Mice
  • Molecular Sequence Data
  • Rats
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid
  • Sequence Homology, Amino Acid
  • Sphingosine
  • Tissue Distribution
  • Tumor Cells, Cultured
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Research

keywords

  • GPCR
  • edg
  • lysophosphatidic acid
  • lysophospholipid
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Identity

International Standard Serial Number (ISSN)

  • 0378-1119

Digital Object Identifier (DOI)

  • 10.1016/s0378-1119(98)00589-7

PubMed ID

  • 9931453
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Additional Document Info

start page

  • 89

end page

  • 99

volume

  • 227

issue

  • 1

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