Clathrin Box in G Protein-coupled Receptor Kinase 2

Takako Shiina, Ken Arai, Shihori Tanabe, Norihiro Yoshida, Tatsuya Haga, Taku Nagao, Hitoshi Kurose

研究成果: ジャーナルへの寄稿学術誌査読

52 被引用数 (Scopus)

抄録

β1-Adrenergic receptor (β1AR) shows the resistance to agonist-induced internalization. However, β1AR can internalize as G protein-coupled receptor kinase 2 (GRK2) is fused to its carboxyl terminus. Internalization of the β1AR and GRK2 fusion protein (β1AR/GRK2) is dependent on dynamin but independent of β-arrestin and phosphorylation. The β1AR/GRK2 fusion protein internalizes via clathrin-coated pits and is found to co-localize with the endosome that contains transferrin. The fusion proteins consisting of β1AR and various portions of GRK2 reveal that the residues 498-502 in the carboxyl-terminal domain of GRK2 are critical to promote internalization of the fusion proteins. This domain contains a consensus sequence of a clathrin-binding motif defined as a clathrin box. In vitro binding assays show that the residues 498-502 of GRK2 bind the amino-terminal domain of clathrin heavy chain to almost the same extent as β-arrestin1. The mutation of the clathrin box in the carboxyl-terminal domain of GRK2 results in the loss of the ability to promote internalization of the fusion protein. GRK2 activity increases and then decreases as the concentration of clathrin heavy chain increases. Taken together, these results imply that GRK2 contains a functional clathrin box and directly interacts with clathrin to modulate its function.

本文言語英語
ページ(範囲)33019-33026
ページ数8
ジャーナルJournal of Biological Chemistry
276
35
DOI
出版ステータス出版済み - 8月 31 2001
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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