Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein.
We report here that apelin (65-77) induces activation of extracellular-regulated kinases (ERKs) in Chinese hamster ovary (CHO) cells expressing the msr/apj receptor. This concentration-dependent activation was transient, peaking at 5 min. Pretreatment of CHO cells with pertussis toxin fully abrogated ERK phosphorylation, whereas overexpression of the beta-adrenergic receptor kinase-1 C-terminal fragment did not alter ERK activation. Transfection with a dominant-negative mutant of Ras was without effect on ERK activation, whereas an inhibitor of many protein kinase C isoforms, GF109203X, strongly decreased it. These results demonstrate that stimulation of the murine msr/apj receptor promotes ERK activation via the alpha subunit of a pertussis toxin-sensitive protein in a Ras-independent pathway.
Masri
Bernard
B
Unité INSERM U-397, CHU Rangueil, Bât. L3, 1 avenue Jean-Poulhès, 31403-Toulouse, France.
Lahlou
Hicham
H
Mazarguil
Honoré
H
Knibiehler
Bernard
B
Audigier
Yves
Y
D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005799:Genes, Dominant; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry; D037342:Pertussis Toxin; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D008301:Maleimides; D010446:Peptide Fragments; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; C114043:BARKct protein, recombinant; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one