The regulatory role of dopamine receptor D1 on PP2A via SUMO-1 modification. 2017

C-Q Yu, and L-Q Yin, and Z-T Tu, and D-W Liu, and W-P Luo
Department of Cardiology, The People's Hospital of Bishan District, Chongqing, China. changqingyu8@sina.com.

OBJECTIVE Renal dopamine receptor D1 played a critical role in the regulation of body blood pressure. Under hypertension, over-phosphorylation of D1 receptor impaired its function. G protein kinase 4 (GRK4) and protein phosphatase 2A (PP2A) exerted the effect to phosphorylate and de-phosphorylate D1 receptor. A current study revealed that the inhibition of GRK4 cannot normalize the phosphorylation level of D1 receptor. Meanwhile, the PP2A was activated under hypertension, indicating abnormal de-phosphorylation function of D1 receptor, the reason for which remains unknown. This study aimed to investigate the effect and mechanism of SUMO-1 modification on the regulation of dopamine receptor D1 to PP2A. METHODS Bioinformatics software predicted SUMO modification site in dopamine receptor D1. Cultured CHO cells were transfected with mutants of renal dopamine receptor D1. Co-immunoprecipitation and Western blot tested the interaction between over-phosphorylated D1 receptor and PP2A. Laser confocal microscopy examined their co-localization. RESULTS Bioinformatics predicted two SUMO modification sites K265 and K402 in dopamine receptor D1. Co-immunoprecipitation assay revealed weakened interaction between PP2A and phosphorylated D1 receptor, impeding the de-phosphorylation and normal function of D1 receptor. CONCLUSIONS Two SUMO modification sites existed in dopamine receptor D1, the phosphorylation of which, due to SUMO modification, can interact with PP2A, leading to the inhibition of D1 de-phosphorylation and normal function, thus providing new insights for treatment and prevention of hypertension.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016466 CHO Cells CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells. CHO Cell,Cell, CHO,Cells, CHO
D017447 Receptors, Dopamine D1 A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES. Dopamine D1 Receptors,Dopamine-D1 Receptor,D1 Receptors, Dopamine,Dopamine D1 Receptor,Receptor, Dopamine-D1
D054648 Protein Phosphatase 2 A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes. PPP2CA Phosphatase,PPP2CB Phosphatase,Protein Phosphatase 2, Catalytic Subunit,Protein Phosphatase 2, Catalytic Subunit, alpha Isoform,Protein Phosphatase 2, Catalytic Subunit, beta Isoform,Protein Phosphatase 2, Regulatory Subunit,Protein Phosphatase 2, Regulatory Subunit A, alpha Isoform,Protein Phosphatase 2, Regulatory Subunit A, beta Isoform,Protein Phosphatase 2, Regulatory Subunit B, alpha Isoform,Protein Phosphatase 2, Regulatory Subunit B, beta Isoform,Protein Phosphatase 2, Regulatory Subunit B, delta Isoform,Protein Phosphatase 2, Regulatory Subunit B, gamma Isoform,Protein Phosphatase 2A, Catalytic Subunit, alpha Isoform,Protein Phosphatase 2A, Catalytic Subunit, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit A , alpha Isoform,Protein Phosphatase 2A, Regulatory Subunit A, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, alpha Isoform,Protein Phosphatase 2A, Regulatory Subunit B, beta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, delta Isoform,Protein Phosphatase 2A, Regulatory Subunit B, gamma Isoform,Protein Phosphatase-2A,Serine Threonine Protein Phosphatase 2A Catalytic Subunit beta Isoform,Serine-Threonine-Protein Phosphatase 2A Catalytic Subunit alpha Isoform,Phosphatase, PPP2CA,Phosphatase, PPP2CB,Protein Phosphatase 2A,Serine Threonine Protein Phosphatase 2A Catalytic Subunit alpha Isoform
D054771 G-Protein-Coupled Receptor Kinase 4 A G-protein-coupled receptor kinase subtype that is primarily expressed in the TESTES and BRAIN. Variants of this subtype exist due to multiple alternative splicing of its mRNA. G-Protein-Coupled Receptor Kinase 4alpha,G-Protein-Coupled Receptor Kinase 4beta,G-Protein-Coupled Receptor Kinase 4delta,G-Protein-Coupled Receptor Kinase 4gamma,GR4K-delta Kinase,GR4K-gamma Kinase,GR4KB Kinase,GRK4 Kinase,GRK4-alpha Kinase,GRK4-beta Kinase,GRK4A Kinase,GRK4C Kinase,GRK4D Kinase,G Protein Coupled Receptor Kinase 4,G Protein Coupled Receptor Kinase 4alpha,G Protein Coupled Receptor Kinase 4beta,G Protein Coupled Receptor Kinase 4delta,G Protein Coupled Receptor Kinase 4gamma,GR4K delta Kinase,GR4K gamma Kinase,GRK4 alpha Kinase,GRK4 beta Kinase
D019295 Computational Biology A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets. Bioinformatics,Molecular Biology, Computational,Bio-Informatics,Biology, Computational,Computational Molecular Biology,Bio Informatics,Bio-Informatic,Bioinformatic,Biologies, Computational Molecular,Biology, Computational Molecular,Computational Molecular Biologies,Molecular Biologies, Computational

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