Ubiquitination of GRK2 Is Required for the β-Arrestin-Biased Signaling Pathway of Dopamine D2 Receptors to Activate ERK Kinases
Abstract
:1. Introduction
2. Results
2.1. GRK2-Mediated Receptor Phosphorylation Directs D2R β-Arrestin Signaling-Pathway-Mediated ERK Activation
2.2. Ubiquitination of GRK2 Is Required for D2R β-Arrestin-Dependent Signaling-Pathway-Mediated ERK Activation
2.3. Activation of the D2R β-Arrestin Signaling Pathway Promotes GRK2 Ubiquitination
2.4. Activation of D2R β-Arrestin Signaling-Pathway-Mediated Mdm2 Nuclear Export
2.5. Src-Mediated GRK2 Tyrosine Phosphorylation Is Required for Mdm2-Mediated GRK2 Ubiquitination
2.6. The Ubiquitination of GRK2 Is Needed for Its Translocation to the Plasma Membrane and Interaction with D2R
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Cell Culture
4.3. Plasmid Constructs
4.4. Immunoprecipitation
4.5. Immunocytochemistry
4.6. ERK1/2 Phosphorylation
4.7. Reporter Gene Assay
4.8. Subcellular Fractionation
4.9. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Liu, H.; Ma, H.; Zeng, X.; Wu, C.; Acharya, S.; Sudan, S.K.; Zhang, X. Ubiquitination of GRK2 Is Required for the β-Arrestin-Biased Signaling Pathway of Dopamine D2 Receptors to Activate ERK Kinases. Int. J. Mol. Sci. 2023, 24, 10031. https://doi.org/10.3390/ijms241210031
Liu H, Ma H, Zeng X, Wu C, Acharya S, Sudan SK, Zhang X. Ubiquitination of GRK2 Is Required for the β-Arrestin-Biased Signaling Pathway of Dopamine D2 Receptors to Activate ERK Kinases. International Journal of Molecular Sciences. 2023; 24(12):10031. https://doi.org/10.3390/ijms241210031
Chicago/Turabian StyleLiu, Haiping, Haixiang Ma, Xingyue Zeng, Chengyan Wu, Srijan Acharya, Sarabjeet Kour Sudan, and Xiaohan Zhang. 2023. "Ubiquitination of GRK2 Is Required for the β-Arrestin-Biased Signaling Pathway of Dopamine D2 Receptors to Activate ERK Kinases" International Journal of Molecular Sciences 24, no. 12: 10031. https://doi.org/10.3390/ijms241210031