Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.
The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl ... cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.
Mesh Terms:
Adenylate Cyclase, Adrenergic beta-Agonists, Animals, Arrestins, Biological Transport, CHO Cells, Cricetinae, Cyclic AMP-Dependent Protein Kinases, G-Protein-Coupled Receptor Kinase 5, G-Protein-Coupled Receptor Kinases, Humans, Phosphorylation, Protein-Serine-Threonine Kinases, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Recombinant Fusion Proteins, beta-Adrenergic Receptor Kinases
Adenylate Cyclase, Adrenergic beta-Agonists, Animals, Arrestins, Biological Transport, CHO Cells, Cricetinae, Cyclic AMP-Dependent Protein Kinases, G-Protein-Coupled Receptor Kinase 5, G-Protein-Coupled Receptor Kinases, Humans, Phosphorylation, Protein-Serine-Threonine Kinases, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Recombinant Fusion Proteins, beta-Adrenergic Receptor Kinases
J. Biol. Chem.
Date: Sep. 15, 2000
PubMed ID: 10862778
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