title: Role of epidermal growth factor receptor transactivation in alpha1B-adrenoceptor phosphorylation.
abstract: Phosphorylation of G protein-coupled receptors is one of the earliest events that regulate their function. Current evidence indicates that homologous desensitization of these receptors mainly involves G protein-coupled receptor kinases whereas in heterologous desensitization second messenger-activated kinases play key roles. Recent data show that transactivation of EGF (epidermal growth factor) receptors may also play a role in receptor phosphorylation. The role of this process was studied for the alpha1B-adrenoceptor phosphorylation induced by agents acting through different processes using inhibitors to block the EGF receptor transactivation process at different levels. Experiments were performed using transfected rat-1 fibroblasts that express alpha1B-adrenoceptors in a stably fashion. A metalloproteinase inhibitor, an anti-heparin-binding-EGF-selective antibody, and a selective EGF-receptor kinase inhibitor blocked the alpha1B-adrenoceptor phosphorylation induced by noradrenaline or endothelin-1. Our results indicate that shedding of heparin-binding-EGF, transactivation of EGF receptors plays a more general role in alpha1B-adrenoceptor phosphorylation than previously anticipated. It is possible that other receptors/channels could be modulated through a similar pathway.
authors.affiliation: Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado postal 70-248, México, DF 04510, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Casas-González
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009638:Norepinephrine / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: C547718:Adra1b protein, rat; D000316:Adrenergic alpha-Agonists; D000730:Androstadienes; D000906:Antibodies; D019332:Endothelin-1; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D013876:Thiophenes; D020032:Tyrphostins; C101044:RTKI cpd; D010649:Phenylalanine; D004815:Epidermal Growth Factor; C080985:batimastat; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine; D000077191:Wortmannin