Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist.
EDG-1, an inducible G-protein-coupled receptor from vascular endothelial cells, is a high affinity receptor for sphingosine 1-phosphate (SPP) (Lee, M-J., van Brocklyn, J. R., Thangada, S., Liu, C. H., Hand, A. R., Menzeleev, R., Spiegel, S., and Hla, T. (1998) Science 279, 1552-1555). In this study, we show that lysophosphatidic acid (LPA), a platelet-derived bioactive lipid structurally related to SPP, is an agonist for EDG-1. LPA binds to EDG-1 receptor with an apparent Kd of 2.3 microM. In addition, LPA binding to EDG-1 induces receptor phosphorylation, mitogen-activated protein kinase activation, as well as Rho-dependent morphogenesis and P-cadherin expression. These data suggest that LPA is a low-affinity agonist for EDG-1. Activation of the endothelial receptor EDG-1 by platelet-derived lipids LPA and SPP may be important in thrombosis and angiogenesis, conditions in which critical platelet-endothelial interactions occur.
Lee
M J
MJ
Department of Physiology, University of Connecticut School of Medicine, Farmington, Connecticut 06030, USA.
Thangada
S
S
Liu
C H
CH
Thompson
B D
BD
Hla
T
T
D002454:Cell Differentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000819:agonists*; D007700:Kinetics; D008024:Ligands; D008246:Lysophospholipids / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D014162:Transfection
D017874:Immediate-Early Proteins; D008024:Ligands; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid