Separation of the structural requirements for agonist-promoted activation and sequestration of the beta-adrenergic receptor.
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.
Cheung
A H
AH
Department of Molecular Pharmacology and Biochemistry, Merck, Sharp, and Dohme Research Laboratories, Rahway, New Jersey 07065.
Dixon
R A
RA
Hill
W S
WS
Sigal
I S
IS
Strader
C D
CD
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D007545:Isoproterenol