Prolyl hydroxylase 2: a novel regulator of β2 -adrenoceptor internalization.
Bottom Line: 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.
Affiliation: Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China.Show MeSH
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Mentions: To determine the role for PHDs in the regulation of β2-AR internalization, PHD1, PHD2, PHD3 or the vector plasmid was transfected into β2-AR-293 cells, respectively. After 48 hrs of expression, these cells were treated with ISO (10 μM) to activate β2-AR. In PHD1- or PHD3-overexpressing cells, ISO stimulation resulted in the loss of surface receptors with a t1/2 of approximately 8 min., similar to the cells expressing β2-AR only (Control). In contrast, PHD2 overexpression resulted in a dramatic decrease in β2-AR internalization rate (t1/2 of approximately 12 min.; Fig. 1A) in response to receptor activation, suggesting a substantial role of PHD2 in the regulation of β2-AR internalization.
Affiliation: Key Laboratory of Arrhythmias, Ministry of Education, China (East Hospital, Tongji University School of Medicine), Shanghai, China.