Low affinity of β 1 -adrenergic receptor for β-arrestins explains the resistance to agonist-induced internalization

Takako Shiina, Taku Nagao, Hitoshi Kurose

研究成果: ジャーナルへの寄稿学術誌査読

13 被引用数 (Scopus)

抄録

It has been reported that β-arrestin is essential for the internalization of many G protein-coupled receptors. Since β 1 -adrenergic receptor (β 1 AR) shows the resistance to agonist-induced internalization, we examine the interaction of β-arrestin with β 1 AR with three different approaches: translocation of β-arrestin to the plasma membrane, direct binding of in vitro translated β-arrestin to intracellular domains of β 1 - and β 2 ARs, inhibition of β 1 - and β 2 AR-stimulated adenylyl cyclase activities by β-arrestin. The enhanced green fluorescent protein (EGFP)-tagged β-arrestin 2 (β-arrestin 2-GFP) translocates to and stays at the plasma membrane by β 2 AR stimulation. β-Arrestin 2-GFP also translocates to the plasma membrane upon β 1 AR stimulation. However, it returns to the cytoplasm 10 - 30 min after agonist stimulation. The amount of β-arrestin bound to the third intracellular loop and the carboxyl tail of β 1 AR is lower than that of β 2 AR. The fusion protein of β-arrestin 1 with glutathione-S-transferase inhibits the β 1 - and β 2 AR-stimulated adenylyl cyclase activities. However, inhibition of the β 1 AR-stimulated activity requires a higher amount of the fusion protein than that of the β 2 AR-stimulated activity. These results suggest that affinity of β 1 AR for β-arrestins is lower than that of β 2 AR, and explains the resistance to agonist-induced internalization. This conclusion is further supported by the finding that β-arrestin can induce internalization of β 1 AR when β-arrestin 1 fused to the carboxyl tail of β 1 AR.

本文言語英語
ページ(範囲)2251-2257
ページ数7
ジャーナルLife Sciences
68
19-20
DOI
出版ステータス出版済み - 4月 6 2001
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 薬理学、毒性学および薬学一般
  • 生化学、遺伝学、分子生物学一般

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