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Science 293 (5530): 702-705

Copyright © 2001 by the American Association for the Advancement of Science

Lysophosphatidylcholine as a Ligand for the Immunoregulatory Receptor G2A

Janusz H. S. Kabarowski,1* Kui Zhu,2* Lu Q. Le,1 Owen N. Witte,13dagger Yan Xu24dagger

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.

1 Department of Microbiology, Immunology, and Molecular Genetics;
2 Department of Cancer Biology, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
3 Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA 90095-1662, USA.
4 Department of Gynecology and Obstetrics, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: owenw{at}microbio.ucla.edu (O.N.W.); xuy{at}ccf.org (Y.X.)



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