Agonist occupancy of a single monomeric element is sufficient to cause internalization of the dimeric beta2-adrenoceptor

Cell Signal. 2007 Sep;19(9):1928-38. doi: 10.1016/j.cellsig.2007.05.002. Epub 2007 May 18.


A range of studies have indicated that many rhodopsin-like, family A G protein-coupled receptors, including the beta(2)-adrenoceptor, exist and probably function as dimers. It is less clear if receptors internalize as dimers and if agonist occupancy of only one element of a dimer is sufficient to cause internalization of a receptor dimer into the cell. We have used a chemogenomic approach to demonstrate that this is the case. Following expression of the wild type beta(2)-adrenoceptor, isoprenaline but not 1-(3''4'-dihydroxyphenyl)-3-methyl-1-butanone, which does not have significant affinity for the wild type receptor, caused receptor internalization. By contrast, 1-(3'4'-dihydroxyphenyl)-3-methyl-1-butanone, but not isoprenaline that does not have high affinity for the mutated receptor, caused internalization of Asp(113)Serbeta(2)-adrenoceptor. Following co-expression of wild type and Asp(113)Serbeta(2)-adrenoceptors each of isoprenaline and 1-(3'4'-dihydroxyphenyl)-3-methyl-1-butanone caused the co-internalization of both of these two forms of the receptor. Co-expressed wild type and Asp(113)Serbeta(2)-adrenoceptors were able to be co-immunoprecipitated and 1-(3'4'-dihydroxyphenyl)-3-methyl-1-butanone produced internalization of the wild type receptor that was not prevented by the beta-adrenoceptor antagonist propranolol that binds with high affinity only to the wild type receptor. These results demonstrate that agonist occupancy of either single binding site of the beta(2)-adrenoceptor dimer is sufficient to cause internalization of the dimer and that antagonist occupation of one of the two ligand binding sites is unable to prevent agonist-mediated internalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists*
  • Adrenergic beta-Agonists / pharmacology*
  • Cell Line
  • Dimerization
  • Doxycycline / pharmacology
  • Endocytosis / drug effects*
  • Humans
  • Isoproterenol / pharmacology
  • Membrane Glycoproteins / metabolism
  • Mutant Proteins / metabolism
  • Propranolol / pharmacology
  • Viral Envelope Proteins / metabolism


  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • G protein, vesicular stomatitis virus
  • Membrane Glycoproteins
  • Mutant Proteins
  • Viral Envelope Proteins
  • Propranolol
  • Isoproterenol
  • Doxycycline