ArticleBritish journal of pharmacology2013
ARF6 and GASP-1 are post-endocytic sorting proteins selectively involved in the intracellular trafficking of dopamine D₂ receptors mediated by GRK and PKC in transfected cells.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- A systematic review and integrative approach to decode the common molecular link between levodopa response and Parkinson's disease.BMC medical genomics · 2017Pooled it
- The Potential Target Value of ADP-Ribosylation Factor 6 in Insulin Secretion Regulation and the Treatment of Metabolic Disorders.Metabolites · 2026Review
- FDA Drug Repurposing Uncovers Modulators of Dopamine DJournal of medicinal chemistry · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- G Protein-Coupled Receptor Kinase 2 Selectively Enhances β-Arrestin Recruitment to the DBiomolecules · 2023Article
- Unveiling the Differences in Signaling and Regulatory Mechanisms between Dopamine DInternational journal of molecular sciences · 2023Review
- GASP1 enhances malignant phenotypes of breast cancer cells and decreases their response to paclitaxel by forming a vicious cycle with IGF1/IGF1R signaling pathway.Cell death & disease · 2022Article
- New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine DScientific reports · 2021Article
- Anaplastic Lymphoma Kinase Regulates Internalization of the Dopamine D2 Receptor.Molecular pharmacology · 2020Article
- Residues and residue pairs of evolutionary importance differentially direct signaling bias of D2 dopamine receptors.The Journal of biological chemistry · 2019Article
- Endo-lysosomal sorting of G-protein-coupled receptors by ubiquitin: Diverse pathways for G-protein-coupled receptor destruction and beyond.Traffic (Copenhagen, Denmark) · 2019Review
- Effects of social defeat stress on dopamine D2 receptor isoforms and proteins involved in intracellular trafficking.Behavioral and brain functions : BBF · 2018Article
- Delta opioid receptors recycle to the membrane after sorting to the degradation path.Cellular and molecular life sciences : CMLS · 2018Article
- GPCR sorting at multivesicular endosomes.Methods in cell biology · 2015Article
- Mutation of three residues in the third intracellular loop of the dopamine D2 receptor creates an internalization-defective receptor.The Journal of biological chemistry · 2014Article
- Gαs regulates the post-endocytic sorting of G protein-coupled receptors.Nature communications · 2014Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeGPCRs undergo both homologous and heterologous regulatory processes in which receptor phosphorylation plays a critical role. The protein kinases responsible for each pathway are well established; however, other molecular details that characterize each pathway remain unclear. In this study, the molecular mechanisms that determine the differences in the functional roles and intracellular trafficking between homologous and PKC-mediated heterologous internalization pathways for the dopamine D₂ receptor were investigated. EXPERIMENTAL APPROACH: All of the S/T residues located within the intracellular loops of D₂ receptor were mutated, and the residues responsible for GRK- and PKC-mediated internalization were determined in HEK-293 cells and SH-SY5Y cells. The functional role of receptor internalization and the cellular components that determine the post-endocytic fate of internalized D₂ receptors were investigated in the transfected cells. KEY
resultsT134, T225/S228/S229 and S325 were involved in PKC-mediated D₂ receptor desensitization. S229 and adjacent S/T residues mediated the PKC-dependent internalization of D₂ receptors, which induced down-regulation and desensitization. S/T residues within the second intracellular loop and T225 were the major residues involved in GRK-mediated internalization of D₂ receptors, which induced receptor resensitization. ARF6 mediated the recycling of D₂ receptors internalized in response to agonist stimulation. In contrast, GASP-1 mediated the down-regulation of D₂ receptors internalized in a PKC-dependent manner. CONCLUSIONS AND IMPLICATIONS: GRK- and PKC-mediated internalizations of D₂ receptors occur through different intracellular trafficking pathways and mediate distinct functional roles. Distinct S/T residues within D₂ receptors and different sorting proteins are involved in the dissimilar regulation of D₂ receptors by GRK2 and PKC.
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