Open AccessProlyl hydroxylase 2: a novel regulator of β 2 ‐adrenoceptor internalization
Author(s) -
Yan Biao,
Huo Zhaoxia,
Liu Ying,
Lin Xiaoping,
Li Jun,
Peng Luying,
Zhao Hong,
Zhou ZhaoNian,
Liang Xingqun,
Liu Yi,
Zhu Weidong,
Liang Dandan,
Li Li,
Sun Yunfu,
Cui Jianmin,
Chen YiHan
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01268.x
Subject(s) - internalization , signalling , cytosol , microbiology and biotechnology , arrestin , receptor , intracellular , regulator , downregulation and upregulation , chemistry , g protein coupled receptor , biology , signal transduction , biochemistry , enzyme , gene
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.