title: The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway.
abstract: The edg-1 gene encodes an inducible G protein-coupled receptor (GPR) homologue that is induced during the in vitro differentiation of human endothelial cells. The aim of this study was to investigate the G protein-coupling and -signaling properties of the edg-1 polypeptide. The third cytosolic loop (i3) of edg-1 associates with G(i) alpha and G(o) alpha polypeptides in a guanosine 5'-O-(thiotriphosphate)-sensitive manner. Immunoprecipitation of the edg-1 polypeptide in transfected cells results in the co-precipitation of G(i) alpha 1 and G(i) alpha 3 polypeptides. These data strongly suggest that edg-1 is capable of coupling to the Gi pathway. Overexpression of the edg-1 GPR in human embryonic kidney 293 cells results in the sustained activation of the MAP kinase activity that is blocked by pertussis toxin treatment. Moreover, NIH3T3 cells permanently transfected with edg-1 exhibit enhanced MAP kinase and phospholipase A2 activities. These data suggest that the G(i)/mitogen-activated protein kinase pathway is a major signaling pathway regulated by the orphan receptor edg-1.
authors.affiliation: Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Evans
authors.forename: T
authors.initials: T
authors.lastname: Hla
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology*; D004789:Enzyme Activation; D000939:Epitopes; D016193:G1 Phase; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D007668:Kidney; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D016324:Sequence Tagged Sites; D015398:Signal Transduction; D014162:Transfection; D014471:Umbilical Veins; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D000939:Epitopes; D017874:Immediate-Early Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D005982:Glutathione Transferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins