A truncation mutation in the avian β-adrenergic receptor causes agonist-induced internalization and GTP-sensitive agonist binding characteristic of mammalian receptors

Cornelia Hertel, Mary H. Nunnally, Stephen K F Wong, Elizabeth A. Murphy, Elliott M. Ross, John P. Perkins

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Abstract

Recombinant turkey erythrocyte β-adrenergic receptors expressed in murine L cells exhibited characteristic avian subtype selectivity for agonists and antagonists. In 10 of the 11 clones studies, no agonist-induced internalization of receptor was observed, although agonist-induced uncoupling of receptor and adenylyl cyclase occurred rapidly. GTP caused little or no decrease in affinity for β-adrenergic agonists. Such behavior is commonly observed in avian erythrocytes. In contrast, one clone was susceptible to agonist-induced receptor internalization and down-regulation even though it exhibited characteristic avian β-adrenergic ligand-binding properties. The affinity of this variant receptor for agonists was also notably reduced by GTP. Electrophoresis of affinity-labeled receptor from this clone indicated an apparent size of about 33 kDa, about 12 kDa less than that of the native or recombinant turkey β-adrenergic receptor. Genomic DNA from this cell line that encodes the receptor was cloned and partially sequenced. The coding region of the original receptor cDNA was interrupted after codon 412 (out of 483) and was followed by 36 base pairs of novel sequence prior to the first in-frame stop codon. These results suggest that the lack of both hormone-induced internalization and GTP-sensitive, high affinity binding of agonists that is characteristic of the β-adrenergic receptor in avian erythrocytes is due to intrinsic properties of the receptor. The restoration of these phenomena in a C-terminally truncated mutant receptor suggests the importance of the C-terminal domain in determining these processes.

Original languageEnglish (US)
Pages (from-to)17988-17994
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number29
StatePublished - Nov 12 1990

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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