Role of epidermal growth factor receptor transactivation in alpha1B-adrenoceptor phosphorylation

Eur J Pharmacol. 2006 Aug 7;542(1-3):31-6. doi: 10.1016/j.ejphar.2006.05.031. Epub 2006 May 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Androstadienes / pharmacology
  • Animals
  • Antibodies / pharmacology
  • Cell Line
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Endothelin-1 / pharmacology
  • Epidermal Growth Factor / immunology
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • ErbB Receptors / physiology*
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Norepinephrine / pharmacology
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Quinazolines
  • Rats
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thiophenes / pharmacology
  • Tyrphostins / pharmacology
  • Wortmannin


  • Adra1b protein, rat
  • Adrenergic alpha-Agonists
  • Androstadienes
  • Antibodies
  • Endothelin-1
  • Hbegf protein, rat
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Quinazolines
  • Receptors, Adrenergic, alpha-1
  • Thiophenes
  • Tyrphostins
  • RTKI cpd
  • Phenylalanine
  • Epidermal Growth Factor
  • batimastat
  • ErbB Receptors
  • Tetradecanoylphorbol Acetate
  • Norepinephrine
  • Wortmannin