RETRACTED: Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A.
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.
Kabarowski
J H
JH
Department of Microbiology, Immunology, and Molecular Genetics, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Zhu
K
K
Le
L Q
LQ
Witte
O N
ON
Xu
Y
Y
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018797:Cell Cycle Proteins; C115270:G2A receptor; D008024:Ligands; D008244:Lysophosphatidylcholines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium