Article: article from journal or magazin.
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
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.
Adrenergic beta-Agonists/metabolism, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Cell Line, Cell Membrane/metabolism, DNA/genetics, Epinephrine/metabolism, Epinephrine/pharmacology, Inositol Phosphates/metabolism, Kinetics, Models, Structural, Molecular Sequence Data, Mutagenesis, Site-Directed, Phenethylamines/metabolism, Protein Conformation, Receptors, Adrenergic, beta/genetics, Receptors, Adrenergic, beta/metabolism, Tetralones, Transfection
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