Abstract
The molecular basis for the desensitization of beta 2-adrenergic receptors was investigated by oligonucleotide-directed mutagenesis. beta-Adrenergic receptor mutants containing deletions within the sixth hydrophilic domain that failed to couple to Gs and stimulate adenylyl cyclase did not undergo agonist-mediated sequestration. In contrast, all receptor mutants that displayed Gs coupling were sequestered away from the cell surface in response to isoproterenol. Progressive truncation of the C-terminus of the receptor resulted in decreases in the initial rates of receptor sequestration and functional uncoupling, although the final extent of these desensitization processes was not affected by the mutations. These data suggest that structural features of the beta 2-adrenergic receptor that are involved in receptor activation are also essential for mediating the subsequent inactivation caused by the sequestration of the receptor from the cell surface.
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