The carboxyl terminus of the hamster β-adrenergic receptor expressed in mouse L cells is not required for receptor sequestration

Abstract The structural basis for agonist-mediated sequestration and desensitization of the β-adrenergic receptor (βAR) was examined by oligonucleotide-directed mutagenesis of the hamster βAR gene and expression of the mutant genes in mouse L cells. Treatment of these cells with the agonist isoproterenol corresponded to a desensitization of βAR activity. A mutant receptor that bound agonist but did not couple to adenylate cyclase showed a dramatically reduced sequestration response to agonist stimulation. In contrast, βAR mutants in which the C-terminus was truncated and/or in which two regions that have been proposed as phosphorylation substrates for cAMP-dependent protein kinase were removed showed normal sequestration responses. These results demonstrate that agonist-mediated sequestration of the βAR can occur in the absence of the C-terminus of the protein and reveal a strong correlation between effective coupling to G s and sequestration.