Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1.
The sphingolipid metabolite sphingosine-1-phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation Gene-1. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.
Lee
M J
MJ
Department of Physiology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Van Brocklyn
J R
JR
Thangada
S
S
Liu
C H
CH
Hand
A R
AR
Menzeleev
R
R
Spiegel
S
S
Hla
T
T
D015820:Cadherins / Q000096:biosynthesis*; D002449:Cell Aggregation; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D017781:Genes, Immediate-Early; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007365:Intercellular Junctions / Q000648:ultrastructure*; D008024:Ligands; D008246:Lysophospholipids; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009024:Morphogenesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014162:Transfection; D020741:rho GTP-Binding Proteins
D015820:Cadherins; D017874:Immediate-Early Proteins; D008024:Ligands; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D019950:Mitogen-Activated Protein Kinase 1; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D013110:Sphingosine