Truncation of the extended carboxyl-terminal domain increases the expression and regulatory activity of the avian β-adrenergic receptor

Eric M. Parker, Elliott M. Ross

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Abstract

A series of mutant avian β-adrenergic receptors with progressively truncated carboxyl termini have been expressed in insect and mammalian cells. Removal of 18-124 amino acid residues caused multiple phenotypic changes in the receptor. Membranes from cells that expressed the truncated receptors displayed elevated basal (2- to 3-fold) and agonist-stimulated adenylylcyclase activities. Adenylylcyclase activity in these membranes also displayed greater stimulation in response to partial agonists. Activity was also markedly stimulated by β-adrenergic ligands that are usually considered to be antagonists (alprenolol, >4-fold; propranolol, ∼2-fold). Wild type receptor did not mediate a response to these classical antagonists. After purification and reconstitution with G., the truncated receptors did not appear to be more active than the wild type. Guanine nucleotides modulated the affinity of agonist for the truncated receptors, whereas the affinity of agonist for the wild type receptor was not altered by guanine nucleotides. The truncated receptors were solubilized from the membrane more efficiently and were more susceptible to amino-terminal proteolysis than was the wild type protein. These results suggest interaction of the carboxyl terminus of the avian β-adrenergic receptor with cellular regulatory or structural elements.

Original languageEnglish (US)
Pages (from-to)9987-9996
Number of pages10
JournalJournal of Biological Chemistry
Volume266
Issue number15
StatePublished - 1991

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Guanine Nucleotides
Adrenergic Receptors
Alprenolol
Membranes
Propranolol
Adrenergic Agents
Proteolysis
Insects
Cell Membrane
Ligands
Amino Acids
Purification
Cells
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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abstract = "A series of mutant avian β-adrenergic receptors with progressively truncated carboxyl termini have been expressed in insect and mammalian cells. Removal of 18-124 amino acid residues caused multiple phenotypic changes in the receptor. Membranes from cells that expressed the truncated receptors displayed elevated basal (2- to 3-fold) and agonist-stimulated adenylylcyclase activities. Adenylylcyclase activity in these membranes also displayed greater stimulation in response to partial agonists. Activity was also markedly stimulated by β-adrenergic ligands that are usually considered to be antagonists (alprenolol, >4-fold; propranolol, ∼2-fold). Wild type receptor did not mediate a response to these classical antagonists. After purification and reconstitution with G., the truncated receptors did not appear to be more active than the wild type. Guanine nucleotides modulated the affinity of agonist for the truncated receptors, whereas the affinity of agonist for the wild type receptor was not altered by guanine nucleotides. The truncated receptors were solubilized from the membrane more efficiently and were more susceptible to amino-terminal proteolysis than was the wild type protein. These results suggest interaction of the carboxyl terminus of the avian β-adrenergic receptor with cellular regulatory or structural elements.",
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AU - Ross, Elliott M.

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N2 - A series of mutant avian β-adrenergic receptors with progressively truncated carboxyl termini have been expressed in insect and mammalian cells. Removal of 18-124 amino acid residues caused multiple phenotypic changes in the receptor. Membranes from cells that expressed the truncated receptors displayed elevated basal (2- to 3-fold) and agonist-stimulated adenylylcyclase activities. Adenylylcyclase activity in these membranes also displayed greater stimulation in response to partial agonists. Activity was also markedly stimulated by β-adrenergic ligands that are usually considered to be antagonists (alprenolol, >4-fold; propranolol, ∼2-fold). Wild type receptor did not mediate a response to these classical antagonists. After purification and reconstitution with G., the truncated receptors did not appear to be more active than the wild type. Guanine nucleotides modulated the affinity of agonist for the truncated receptors, whereas the affinity of agonist for the wild type receptor was not altered by guanine nucleotides. The truncated receptors were solubilized from the membrane more efficiently and were more susceptible to amino-terminal proteolysis than was the wild type protein. These results suggest interaction of the carboxyl terminus of the avian β-adrenergic receptor with cellular regulatory or structural elements.

AB - A series of mutant avian β-adrenergic receptors with progressively truncated carboxyl termini have been expressed in insect and mammalian cells. Removal of 18-124 amino acid residues caused multiple phenotypic changes in the receptor. Membranes from cells that expressed the truncated receptors displayed elevated basal (2- to 3-fold) and agonist-stimulated adenylylcyclase activities. Adenylylcyclase activity in these membranes also displayed greater stimulation in response to partial agonists. Activity was also markedly stimulated by β-adrenergic ligands that are usually considered to be antagonists (alprenolol, >4-fold; propranolol, ∼2-fold). Wild type receptor did not mediate a response to these classical antagonists. After purification and reconstitution with G., the truncated receptors did not appear to be more active than the wild type. Guanine nucleotides modulated the affinity of agonist for the truncated receptors, whereas the affinity of agonist for the wild type receptor was not altered by guanine nucleotides. The truncated receptors were solubilized from the membrane more efficiently and were more susceptible to amino-terminal proteolysis than was the wild type protein. These results suggest interaction of the carboxyl terminus of the avian β-adrenergic receptor with cellular regulatory or structural elements.

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