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

Patricia Casas-González1, J Adolfo García-Sáinz

  • 1Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado postal 70-248, México, DF 04510, Mexico.

European Journal of Pharmacology
|July 11, 2006
PubMed

Insights

Epidermal growth factor (EGF) receptor transactivation plays a key role in alpha1B-adrenoceptor phosphorylation. This process, involving heparin-binding-EGF shedding, is more widespread than previously understood for G protein-coupled receptor regulation.

Area of Science:

  • Cellular signaling
  • Molecular pharmacology
  • G protein-coupled receptor regulation

Background:

  • Receptor phosphorylation is crucial for G protein-coupled receptor (GPCR) function.
  • Homologous desensitization involves GPCR kinases, while heterologous desensitization involves second messenger-activated kinases.
  • Recent findings suggest epidermal growth factor (EGF) receptor transactivation may contribute to GPCR phosphorylation.

Purpose of the Study:

  • To investigate the role of EGF receptor transactivation in alpha1B-adrenoceptor phosphorylation.
  • To determine if EGF receptor transactivation is involved in phosphorylation induced by various signaling agents.
  • To elucidate the mechanism of alpha1B-adrenoceptor phosphorylation via EGF receptor transactivation.

Main Methods:

  • Utilized transfected rat-1 fibroblasts stably expressing alpha1B-adrenoceptors.
  • Employed specific inhibitors: metalloproteinase inhibitor, anti-heparin-binding-EGF antibody, and EGF receptor kinase inhibitor.
  • Assessed alpha1B-adrenoceptor phosphorylation induced by noradrenaline and endothelin-1.

Main Results:

  • Inhibition of metalloproteinase, heparin-binding-EGF, or EGF receptor kinase blocked alpha1B-adrenoceptor phosphorylation.
  • Noradrenaline and endothelin-1 induced alpha1B-adrenoceptor phosphorylation via EGF receptor transactivation.
  • Shedding of heparin-binding-EGF is a critical step in this signaling pathway.

Conclusions:

  • EGF receptor transactivation, mediated by heparin-binding-EGF shedding, plays a significant role in alpha1B-adrenoceptor phosphorylation.
  • This pathway is more general in regulating alpha1B-adrenoceptor phosphorylation than previously recognized.
  • Similar mechanisms may modulate other receptors and ion channels.

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