Prolyl hydroxylase 2: A novel regulator of β 2-adrenoceptor internalization

Biao Yan; Zhaoxia Huo; Ying Liu; Xiaoping Lin; Jun Li; Luying Peng; Hong Zhao; Zhao Nian Zhou; Xingqun Liang; Yi Liu; Weidong Zhu; Dandan Liang; Li Li; Yunfu Sun; Jianmin Cui; Yi Han Chen

doi:10.1111/j.1582-4934.2011.01268.x

Prolyl hydroxylase 2: A novel regulator of β ₂-adrenoceptor internalization

Biao Yan, Zhaoxia Huo, Ying Liu, Xiaoping Lin, Jun Li, Luying Peng, Hong Zhao, Zhao Nian Zhou, Xingqun Liang, Yi Liu, Weidong Zhu, Dandan Liang, Li Li, Yunfu Sun, Jianmin Cui, Yi Han Chen

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 β ₂-adrenoceptor (β ₂-AR) signalling. Here we show that PHD2 can modulate the rate of β ₂-AR internalization through interactions with β-arrestin 2. PHD2 hydroxylates β-arrestin 2 at the proline (Pro) ¹⁷⁶, Pro ¹⁷⁹ and Pro ¹⁸¹ sites, which retards the recruitment of β-arrestin 2 to the plasma membrane and inhibits subsequent co-internalization with β ₂-AR into the cytosol. β ₂-AR internalization is critical to control the temporal and spatial aspects of β ₂-AR signalling. Identifying novel regulators of β ₂-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 β ₂-AR signalling dysregulation.

Original language	English
Pages (from-to)	2712-2722
Number of pages	11
Journal	Journal of Cellular and Molecular Medicine
Volume	15
Issue number	12
DOIs	https://doi.org/10.1111/j.1582-4934.2011.01268.x
State	Published - Dec 2011

Keywords

Hydroxylation
Internalization
Prolyl hydroxylase
β -adrenoceptor
β-arrestin 2

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10.1111/j.1582-4934.2011.01268.x

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title = "Prolyl hydroxylase 2: A novel regulator of β 2-adrenoceptor internalization",

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 β 2-adrenoceptor (β 2-AR) signalling. Here we show that PHD2 can modulate the rate of β 2-AR internalization through interactions with β-arrestin 2. PHD2 hydroxylates β-arrestin 2 at the proline (Pro) 176, Pro 179 and Pro 181 sites, which retards the recruitment of β-arrestin 2 to the plasma membrane and inhibits subsequent co-internalization with β 2-AR into the cytosol. β 2-AR internalization is critical to control the temporal and spatial aspects of β 2-AR signalling. Identifying novel regulators of β 2-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 β 2-AR signalling dysregulation.",

keywords = "Hydroxylation, Internalization, Prolyl hydroxylase, β -adrenoceptor, β-arrestin 2",

author = "Biao Yan and Zhaoxia Huo and Ying Liu and Xiaoping Lin and Jun Li and Luying Peng and Hong Zhao and Zhou, {Zhao Nian} and Xingqun Liang and Yi Liu and Weidong Zhu and Dandan Liang and Li Li and Yunfu Sun and Jianmin Cui and Chen, {Yi Han}",

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language = "English",

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T2 - A novel regulator of β 2-adrenoceptor internalization

AU - Yan, Biao

AU - Huo, Zhaoxia

AU - Liu, Ying

AU - Lin, Xiaoping

AU - Li, Jun

AU - Peng, Luying

AU - Zhao, Hong

AU - Zhou, Zhao Nian

AU - Liang, Xingqun

AU - Liu, Yi

AU - Zhu, Weidong

AU - Liang, Dandan

AU - Li, Li

AU - Sun, Yunfu

AU - Cui, Jianmin

AU - Chen, Yi Han

PY - 2011/12

Y1 - 2011/12

N2 - 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 β 2-adrenoceptor (β 2-AR) signalling. Here we show that PHD2 can modulate the rate of β 2-AR internalization through interactions with β-arrestin 2. PHD2 hydroxylates β-arrestin 2 at the proline (Pro) 176, Pro 179 and Pro 181 sites, which retards the recruitment of β-arrestin 2 to the plasma membrane and inhibits subsequent co-internalization with β 2-AR into the cytosol. β 2-AR internalization is critical to control the temporal and spatial aspects of β 2-AR signalling. Identifying novel regulators of β 2-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 β 2-AR signalling dysregulation.

AB - 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 β 2-adrenoceptor (β 2-AR) signalling. Here we show that PHD2 can modulate the rate of β 2-AR internalization through interactions with β-arrestin 2. PHD2 hydroxylates β-arrestin 2 at the proline (Pro) 176, Pro 179 and Pro 181 sites, which retards the recruitment of β-arrestin 2 to the plasma membrane and inhibits subsequent co-internalization with β 2-AR into the cytosol. β 2-AR internalization is critical to control the temporal and spatial aspects of β 2-AR signalling. Identifying novel regulators of β 2-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 β 2-AR signalling dysregulation.

KW - Hydroxylation

KW - Internalization

KW - Prolyl hydroxylase

KW - β -adrenoceptor

KW - β-arrestin 2

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SN - 1582-1838

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JO - Journal of Cellular and Molecular Medicine

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ER -

Prolyl hydroxylase 2: A novel regulator of β ₂-adrenoceptor internalization

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