AGAP2 [Arf (ADP-ribosylation factor) GAP (GTPase-activating protein) with GTP-binding-protein-like, ankyrin repeat and PH (pleckstrin homology) domains] is a multidomain Arf GAP that was shown to promote the fast recycling of transferrin receptors. In the present study we tested the hypothesis that AGAP2 regulates the trafficking of β2-adrenergic receptors. We found that AGAP2 formed a complex with β-arrestin1 and β-arrestin2, proteins that are known to regulate β2-adrenergic receptor signalling and trafficking. AGAP2 co-localized with β-arrestin2 on the plasma membrane, and knockdown of AGAP2 expression reduced plasma membrane association of β-arrestin2 upon β2-adrenergic receptor activation. AGAP2 also co-localized with internalized β2-adrenergic receptors on endosomes, and overexpression of AGAP2 slowed accumulation of β2-adrenergic receptor in the perinuclear recycling endosomes. In contrast, knockdown of AGAP2 expression prevented the recycling of the β2-adrenergic receptor back to the plasma membrane. In addition, AGAP2 formed a complex with endogenous ERK (extracellular-signal-regulated kinase) and overexpression of AGAP2 potentiated ERK phosphorylation induced by β2-adrenergic receptors. Taken together, these results support the hypothesis that AGAP2 plays a role in the signalling and recycling of β2-adrenergic receptors.
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Research Article|
May 31 2013
The Arf GAP AGAP2 interacts with β-arrestin2 and regulates β2-adrenergic receptor recycling and ERK activation
Yuanjun Wu;
Yuanjun Wu
*Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
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Yu Zhao;
Yu Zhao
*Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
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Xiaojie Ma;
Xiaojie Ma
*Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
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Yunjuan Zhu;
Yunjuan Zhu
†Department of Urology, Tianjin Medical University, Tianjin, 300070 China
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Jaimin Patel;
Jaimin Patel
*Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
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Zhongzhen Nie
Zhongzhen Nie
1
*Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
‡Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
1To whom correspondence should be addressed (email znie@ufl.edu).
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Publisher: Portland Press Ltd
Received:
June 21 2012
Revision Received:
March 07 2013
Accepted:
March 26 2013
Accepted Manuscript online:
March 26 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 452 (3): 411–421.
Article history
Received:
June 21 2012
Revision Received:
March 07 2013
Accepted:
March 26 2013
Accepted Manuscript online:
March 26 2013
Citation
Yuanjun Wu, Yu Zhao, Xiaojie Ma, Yunjuan Zhu, Jaimin Patel, Zhongzhen Nie; The Arf GAP AGAP2 interacts with β-arrestin2 and regulates β2-adrenergic receptor recycling and ERK activation. Biochem J 15 June 2013; 452 (3): 411–421. doi: https://doi.org/10.1042/BJ20121004
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