Details

Autor(en) / Beteiligte

• Kjelsberg, M A
• Cotecchia, S
• Ostrowski, J
• Caron, M G
• Lefkowitz, R J

Titel

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

Ist Teil von

• The Journal of biological chemistry, 1992-01, Vol.267 (3), p.1430-1433

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1992

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.