1997
DOI: 10.1074/jbc.272.3.1822
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Mutation of Asn111 in the Third Transmembrane Domain of the AT1A Angiotensin II Receptor Induces Its Constitutive Activation

Abstract: Constitutive activation of G protein-coupled receptors, initially reported by Cotecchia et al. (1) for the ␣ 1 -adrenergic receptor, is now well documented and has been extended to many other members of this large family (2-21). Moreover, mutations inducing receptor constitutive activation have been found to be associated with human diseases (13-16). Data on the ␤ 2 -adrenergic receptors have prompted their authors to propose an extended version of the ternary complex model, based on the existence of active a… Show more

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Cited by 154 publications
(139 citation statements)
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References 29 publications
(38 reference statements)
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“…Partial agonist activity of antagonists has been reported (Cho et al, 1996;Groblewski et al, 1997) induction of partial agonist properties of the AT 2 -speci®c peptide ligand CGP 42112A [27% of the response to the agonist (Sar 1 )AII] is associated with an increased a nity for the mutant AT 1A angiotensin II receptor (Groblewski et al, 1997). Thus, with the exception of CGP 42112A, partial agonist activity was not accompanied by an increased binding a nity at this latter receptor.…”
Section: Partial Agonist Activity Of Antagonists At Mutant G-protein-mentioning
confidence: 77%
“…Partial agonist activity of antagonists has been reported (Cho et al, 1996;Groblewski et al, 1997) induction of partial agonist properties of the AT 2 -speci®c peptide ligand CGP 42112A [27% of the response to the agonist (Sar 1 )AII] is associated with an increased a nity for the mutant AT 1A angiotensin II receptor (Groblewski et al, 1997). Thus, with the exception of CGP 42112A, partial agonist activity was not accompanied by an increased binding a nity at this latter receptor.…”
Section: Partial Agonist Activity Of Antagonists At Mutant G-protein-mentioning
confidence: 77%
“…The marked amplification of the response to the agonist and the moderate changes of K d and K act values are less common, but they were reported for some GPCRs with constitutive activity, such as the Asn-111 mutant of the AT 1A receptor (17).…”
Section: Discussionmentioning
confidence: 99%
“…B a s e d o n a n u m b e r o f pharmacological, mutagenesis and computer-oriented modeling studies [63][64][65][66][67][68][69][70][71][72][73][74][75][76], the general agreement is that a positively-charged residue of Lys199 on transmembrane domain (TM)-5 of the AT1 receptor interacts with the -carboxyl group of Phe8 in Ang II. This interaction is crucial for high affinity binding of Ang II to the receptor.…”
Section: Functional Domains Of the At1 Receptormentioning
confidence: 99%