These authors contributed equally to this paper.
Prolyl hydroxylase 2: a novel regulator of β2-adrenoceptor internalization
Article first published online: 28 NOV 2011
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Journal of Cellular and Molecular Medicine
Volume 15, Issue 12, pages 2712–2722, December 2011
How to Cite
Yan, B., Huo, Z., Liu, Y., Lin, X., Li, J., Peng, L., Zhao, H., Zhou, Z.-N., Liang, X., Liu, Y., Zhu, W., Liang, D., Li, L., Sun, Y., Cui, J. and Chen, Y.-H. (2011), Prolyl hydroxylase 2: a novel regulator of β2-adrenoceptor internalization. Journal of Cellular and Molecular Medicine, 15: 2712–2722. doi: 10.1111/j.1582-4934.2011.01268.x
- Issue published online: 28 NOV 2011
- Article first published online: 28 NOV 2011
- Accepted manuscript online: 21 JAN 2011 09:09AM EST
- Received: August 27, 2010; Accepted: January 19, 2011
- prolyl hydroxylase;
- β-arrestin 2;
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.