Article abstract
Nature Cell Biology 2, 261 - 267 (2000)
Published online: 4 April 2000 | doi:10.1038/35010529
There is a Retraction (March 2006) associated with this Article.
Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1
Yan Xu1,2,6, Kui Zhu1,6, Guiying Hong1, Weihua Wu, Linnea M. Baudhuin1,4, Yi-jin Xiao1 & Derek S. Damron3
Abstract
Sphingosylphosphorylcholine (SPC) is a bioactive lipid that acts as an intracellular and extracellular signalling molecule in numerous biological processes. Many of the cellular actions of SPC are believed to be mediated by the activation of unidentified G-protein-coupled receptors. Here we show that SPC is a high-affinity ligand for an orphan receptor, ovarian cancer G-protein-coupled receptor 1 (OGR1). In OGR1-transfected cells, SPC binds to OGR1 with high affinity (Kd = 33.3 nM) and high specificity and transiently increases intracellular calcium. The specific binding of SPC to OGR1 also activates p42/44 mitogen-activated protein kinases (MAP kinases) and inhibits cell proliferation. In addition, SPC causes internalization of OGR1 in a structurally specific manner.
- Department of Cancer Biology, Division of Anesthesiology and Critical Care Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
- Department of Gynecology and Obstetrics, Division of Anesthesiology and Critical Care Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
- Center for Anesthesiology Research, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
- Current address: Department of Medicine, University of California, Irvine, California 92697, USA
- Department of Chemistry, Cleveland State University, 24th and Euclid Avenue, Cleveland, Ohio 44115, USA
- These authors contributed equally to this work
Correspondence to: Yan Xu1,2,6 e-mail: xuy@ccf.org
