Abstract
Mutations in an intracellular region of the alpha 1B-adrenergic receptor constitutively activate the receptor, resulting in G protein coupling in the absence of agonist, as evidenced by elevated levels of polyphosphoinositide hydrolysis. Remarkably, all 19 possible amino acid substitutions at a single site in this region (alanine 293) confer constitutive activity. This set of mutated receptors exhibits a graded range of elevated biological activities, apparently representing a spectrum of receptor conformations which mimic the "active" state of the wild type receptor. In addition to their constitutive activities, these mutated receptors all demonstrate a higher affinity for agonists, another primary characteristic of the "active" conformation of G protein-coupled receptors. The fact that all possible mutations at this particular site result in increased activity suggests that this region may function to constrain the G protein coupling of the receptor, a constraint which is normally relieved by agonist occupancy.
Keywords
Alpha (finance)ReceptorAdrenergic receptorAmino acidChemistryBiochemistryMedicine
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Publication Info
- Year
- 1992
- Type
- article
- Volume
- 267
- Issue
- 3
- Pages
- 1430-1433
- Citations
- 599
- Access
- Closed
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Michael A. Kjelsberg,
Susanna Cotecchia,
Jerzy Ostrowski
et al.
(1992).
Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation..
Journal of Biological Chemistry
, 267
(3)
, 1430-1433.
https://doi.org/10.1016/s0021-9258(18)45962-5
Identifiers
- DOI
- 10.1016/s0021-9258(18)45962-5