Interaction with β-arrestin determines the difference in internalization behavior between β1- and β2-adrenergic receptors

T. Shiina, A. Kawasaki, T. Nagao, H. Kurose

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Abstract

The β1-adrenergic receptor (β1AR) shows the resistance to agonist-induced internalization. As β-arrestin is important for internalization, we examine the interaction of β-arrestin with β1AR with three different methods: intracellular trafficking of β-arrestin, binding of in vitro translated β-arrestin to intracellular domains of β1- and β2ARs, and inhibition of βAR-stimulated adenylyl cyclase activities by β-arrestin. The green fluorescent protein-tagged β-arrestin 2 translocates to and stays at the plasma membrane by β2AR stimulation. Although green fluorescent protein-tagged β-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after β1AR stimulation. The binding of in vitro translated β-arrestin 1 and β-arrestin 2 to the third intracellular loop and the carboxyl tail of β1AR is lower than that of β2AR. The fusion protein of β-arrestin 1 with glutathione S-transferase inhibits the β1- and β2AR-stimulated adenylyl cyclase activities, although inhibition of the β1AR-stimulated activity requires a higher concentration of the fusion protein than that of the β2AR-stimulated activity. These results suggest that weak interaction of β1AR with β-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that β-arrestin can induce internalization of β1AR when β-arrestin 1 does not dissociate from β1AR by fusing to the carboxyl tail of β1AR.

Original languageEnglish
Pages (from-to)29082-29090
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number37
DOIs
Publication statusPublished - Sep 15 2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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