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Research ArticleArticle

Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors

Bo Cen, Ying Xiong, Lan Ma and Gang Pei
Molecular Pharmacology April 2001, 59 (4) 758-764; DOI: https://doi.org/10.1124/mol.59.4.758
Bo Cen
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Ying Xiong
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Lan Ma
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Gang Pei
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Abstract

β-arrestins have been shown to play important roles in regulation of signaling and desensitization of opioid receptors in many in vivo studies. The current study was carried out to measure the direct interaction of β-arrestins with two functional intracellular domains, the third intracellular loop (I3L) and the carboxyl terminus (CT), of δ-, μ-, and κ-opioid receptors (DOR, MOR, and KOR, respectively). Results from the pull-down assay using glutathioneS-transferase fusion proteins demonstrated that β-arrestins (1 and 2) were able to bind to the I3L of DOR and to the CT of DOR and KOR. Surface plasmon resonance measurement gave similar results with typical dissociation equilibrium constant (K D) values in the micromolar range. The site-directed mutagenesis experiment further revealed that certain specific serine/threonine residues in these receptor domains play a critical role in their interaction with β-arrestins. Taken together, our data clearly indicated that β-arrestins interact differentially with the functional domains of different opioid receptors; this may provide a possible molecular basis for differential regulation of opioid receptors by β-arrestins.

Footnotes

    • Received October 11, 2000.
    • Accepted December 27, 2000.
  • Send reprint requests to: Dr. Gang Pei, Shanghai Institute of Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031. E-mail:gangpei{at}sunm.shcnc.ac.cn

  • This work was supported by the Grants from the National Natural Science Foundation of China (39625015 and 39825110), Chinese Academy of Sciences (KJ951-B1), Ministry of Science and Technology (G1999053907 and G1999054003), National Laboratory of Medical Neurobiology, and the German Max-Planck Society.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 59 (4)
Molecular Pharmacology
Vol. 59, Issue 4
1 Apr 2001
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Research ArticleArticle

Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors

Bo Cen, Ying Xiong, Lan Ma and Gang Pei
Molecular Pharmacology April 1, 2001, 59 (4) 758-764; DOI: https://doi.org/10.1124/mol.59.4.758

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Research ArticleArticle

Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors

Bo Cen, Ying Xiong, Lan Ma and Gang Pei
Molecular Pharmacology April 1, 2001, 59 (4) 758-764; DOI: https://doi.org/10.1124/mol.59.4.758
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