title: The sequence Pro295-Thr311 of the hinge region of oestrogen receptor α is involved in ERK1/2 activation via GPR30 in leiomyoma cells.
abstract: The ERα (oestrogen receptor α)-derived peptide ERα17p activates rapid signalling events in breast carcinoma cells under steroid-deprived conditions. In the present study, we investigated its effects in ELT3 leiomyoma cells under similar conditions. We show that it activates ERK1/2 (extracellular-signal-regulated kinase 1/2), the Gαi protein, the trans-activation of EGFR (epidermal growth factor receptor) and, finally, cell proliferation. It is partially internalized in cells and induces membrane translocation of β-arrestins. The activation of ERK1/2 is abolished by the GPR30 (G-protein-coupled receptor 30) antagonist G15 and GPR30 siRNA. When ERα is down-regulated by prolonged treatment with E2 (oestradiol) or specific ERα siRNA, the peptide response is blunted. Thus the simultaneous presence of GPR30 and ERα is required for the action of ERα17p. In addition, its PLM sequence, which interferes with the formation of the ERα-calmodulin complex, appears to be requisite for the phosphorylation of ERK1/2 and cell proliferation. Hence ERα17p is, to our knowledge, the first known peptide targeting ERα-GPR30 membrane cross-talk and the subsequent receptor-mediated biological effects.
authors.affiliation: Laboratoire Signalisation et Régulations Cellulaires, Institut de Biochimie et de Biologie Moléculaire et Cellulaire, CNRS UMR 8619, Université Paris-Sud, Bâtiment 430, 91405 Orsay Cedex, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Leiber
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, École Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, Tour 23-33, 4 place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burlina
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, École Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, Tour 23-33, 4 place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Cillian
authors.initials: C
authors.lastname: Byrne
authors.affiliation: Laboratoire Signalisation et Régulations Cellulaires, Institut de Biochimie et de Biologie Moléculaire et Cellulaire, CNRS UMR 8619, Université Paris-Sud, Bâtiment 430, 91405 Orsay Cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
authors.affiliation: Institut de Biologie Intégrative (IFR 83), Sorbonne Universités - UPMC Univ Paris 06, IFR83, Case Courrier 25, 7 quai Saint-Bernard, 75252 Paris Cedex 05, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Piesse
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, École Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, Tour 23-33, 4 place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Gonzalez
authors.affiliation: Laboratoire de Cancérologie Mammaire, Institut Jules Bordet, 1 rue Héger Bordet, Brussels 1000, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Leclercq
authors.affiliation: Laboratoire Signalisation et Régulations Cellulaires, Institut de Biochimie et de Biologie Moléculaire et Cellulaire, CNRS UMR 8619, Université Paris-Sud, Bâtiment 430, 91405 Orsay Cedex, France.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Tanfin
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, École Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, Tour 23-33, 4 place Jussieu, 75252 Paris Cedex 05, France yves.jacquot@upmc.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D015153:Blotting, Western; D002147:Calmodulin / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D020239:Receptor Cross-Talk / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D002147:Calmodulin; D047628:Estrogen Receptor alpha; C520305:Gper1 protein, rat; D009842:Oligopeptides; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D004958:Estradiol; C483803:Egfr protein, rat; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: EGFR; ERK1/2; ERα hinge region; GPR30; calmodulin; β-arrestins