• Open Access

Prolyl hydroxylase 2: a novel regulator of β2-adrenoceptor internalization

Authors

  • Biao Yan,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
    3. Department of Biochemistry and Molecular Biology, School of Life Science and Technology, Tongji University, Shanghai, China
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    • These authors contributed equally to this paper.

  • Zhaoxia Huo,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Department of Biochemistry and Molecular Biology, School of Life Science and Technology, Tongji University, Shanghai, China
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    • These authors contributed equally to this paper.

  • Ying Liu,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Department of Biochemistry and Molecular Biology, School of Life Science and Technology, Tongji University, Shanghai, China
    3. Heilongjiang Province Blood Center, Harbin, China
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    • These authors contributed equally to this paper.

  • Xiaoping Lin,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
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    • These authors contributed equally to this paper.

  • Jun Li,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
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  • Luying Peng,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
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  • Hong Zhao,

    1. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
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  • Zhao-Nian Zhou,

    1. Laboratory of Hypoxic Cardiovascular Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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  • Xingqun Liang,

    1. School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego (UCSD), San Diego, CA, USA
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  • Yi Liu,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
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  • Weidong Zhu,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China
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  • Dandan Liang,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China
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  • Li Li,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
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  • Yunfu Sun,

    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China
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  • Jianmin Cui,

    1. Department of Biomedical Engineering and Cardiac Bioelectricity and Arrhythmia Centre, Washington University, St. Louis, MO, USA
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  • Yi-Han Chen

    Corresponding author
    1. Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China
    2. Institute of Medical Genetics, Tongji University (Tongji Hospital, Tongji University School of Medicine), Shanghai, China
    3. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China
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Yi-Han CHEN, Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), 150 Jimo Road, 200120 Shanghai, China. Tel.: +086-21-65989086 Fax: +086-21-56370868 E-mail: yihanchen@hotmail.com

Abstract

Adrenergic receptor (AR)-mediated signalling is modulated by oxygen levels. Prolyl hydroxylases (PHDs) are crucial for intracellular oxygen sensing and organism survival. However, it remains to be clarified whether or how PHDs are involved in the regulation of β2-adrenoceptor (β2-AR) signalling. Here we show that PHD2 can modulate the rate of β2-AR internalization through interactions with β-arrestin 2. PHD2 hydroxylates β-arrestin 2 at the proline (Pro)176, Pro179 and Pro181 sites, which retards the recruitment of β-arrestin 2 to the plasma membrane and inhibits subsequent co-internalization with β2-AR into the cytosol. β2-AR internalization is critical to control the temporal and spatial aspects of β2-AR signalling. Identifying novel regulators of β2-AR internalization will enable us to develop new strategies to manipulate receptor signalling and provide potential targets for drug development in the prevention and treatment of diseases associated with β2-AR signalling dysregulation.

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