Separation of the structural requirements for agonist-promoted activation and sequestration of the beta-adrenergic receptor

AH Cheung, RA Dixon, WS Hill, IS Sigal and CD Strader

Department of Molecular Pharmacology and Biochemistry, Merck, Sharp, and Dohme Research Laboratories, Rahway, New Jersey 07065.

The deletion of residues 222-229 from the hamster beta 2-adrenergic receptor (beta AR) resulted in an inability of the mutant receptor to couple to the guanine nucleotide-binding protein (G protein) Gs and to undergo the agonist-mediated sequestration response that is associated with desensitization [Mol. Pharmacol. 34:132-138 (1989)]. Replacement of this region of the beta AR with the analogous region of the M1- muscarinic acetylcholine receptor restored the sequestration response but not the G protein activation. These data suggest that there is a structural, rather than a functional, relationship between these two processes and demonstrate that G protein coupling is not a prerequisite for receptor sequestration.

Volume 37, Issue 6, pp. 775-779, 06/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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