Abstract
Although the biological actions of the cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis and systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor. We show that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity. Activation of G2A by LPC increased intracellular calcium concentration, induced receptor internalization, activated ERK mitogen-activated protein kinase, and modified migratory responses of Jurkat T lymphocytes. This finding implicates a role for LPC-G2A interaction in the etiology of inflammatory autoimmune disease and atherosclerosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
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Retracted Publication
MeSH terms
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Animals
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Arteriosclerosis / immunology
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Arteriosclerosis / metabolism
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Calcium / metabolism
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Cell Cycle Proteins / metabolism*
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Cell Line
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Chemotaxis, Leukocyte
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Humans
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Jurkat Cells
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Ligands
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Lupus Erythematosus, Systemic / immunology
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Lupus Erythematosus, Systemic / metabolism
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Lymphocyte Activation
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Lysophosphatidylcholines / metabolism*
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Lysophosphatidylcholines / pharmacology
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Mitogen-Activated Protein Kinases / metabolism
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Phosphorylcholine / analogs & derivatives
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Phosphorylcholine / metabolism
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Phosphorylcholine / pharmacology
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Radioligand Assay
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Receptors, Cell Surface / metabolism*
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Receptors, G-Protein-Coupled*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Sphingosine / analogs & derivatives
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Sphingosine / metabolism
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Sphingosine / pharmacology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes / physiology
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Tetradecanoylphorbol Acetate / pharmacology
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Transfection
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Virulence Factors, Bordetella / pharmacology
Substances
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Cell Cycle Proteins
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G2A receptor
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Ligands
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Lysophosphatidylcholines
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Recombinant Fusion Proteins
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Virulence Factors, Bordetella
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sphingosine phosphorylcholine
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Phosphorylcholine
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Mitogen-Activated Protein Kinases
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Sphingosine
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Tetradecanoylphorbol Acetate
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Calcium