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A growing family of receptor genes for lysophosphatidic acid (LPA) and other lysophospholipids (LPs)

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Abstract

A missing component in the experimental analysis of cell signaling by extracellular lysophospholipids such as lysophosphatidic acid (LPA) or sphingosine-1-phosphate (S1P) has been cloned receptors. Through studies on the developing brain, the first such receptor gene (referred to asvzg-1) was identified, representing a member of the G-protein coupled receptor (GPCR) super family(1). Here we review the neurobiological approach that led to both its cloning and identification as a receptor for LPA, along with related expression data. Summarized sequence and genomic structure analyses indicate that this first, functionally identified receptor is encoded by a member of a growing gene family that divides into at least two subgroups: genes most homologous to the high-affinity LPA receptor encoded byvzg-1, and those more homologous to an orphan receptor geneedg-1 that has recently been identified as a S1P receptor. A provisional nomenclature is proposed, based on published functional ligand actions, amino acid composition and genomic structure whereby the receptors encoded by these genes are referred to as lysophospholipid (LP) receptors, with subgroups distinguished by letter and number subscripts (e.g., LPA1 for Vzg-1, and LPB1 for Edg-1). Presented expression data support the recently published work indicating that members of the LPB1 subgroup are receptors for the structurally-related molecule, S1P. The availability of cloned LP receptors will enhance the analysis of the many documented LP effects, while their prominent expression in the nervous system indicates significant but as yet unknown roles in development, normal function, and neuropathology.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, University of California, San Diego, CA

    Jerold Chun & James J. A. Contos

  2. Neurosciences Program, School of Medicine, University of California, San Diego, CA

    Jerold Chun & James J. A. Contos

  3. Biomedical Sciences Program, School of Medicine, University of California, San Diego, CA

    Jerold Chun

  4. Allelix Biopharmaceuticals, Mississauga, Canada

    Donald Munroe

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Chun, J., Contos, J.J.A. & Munroe, D. A growing family of receptor genes for lysophosphatidic acid (LPA) and other lysophospholipids (LPs). Cell Biochem Biophys 30, 213–242 (1999). https://doi.org/10.1007/BF02738068

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