Affinage

GRK4

G protein-coupled receptor kinase 4 · UniProt P32298

Length
578 aa
Mass
66.6 kDa
Annotated
2026-06-10
39 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRK4 is a palmitoylated G protein-coupled receptor kinase that phosphorylates agonist-occupied GPCRs to drive their desensitization, established initially against the purified beta2-adrenergic receptor and luteinizing hormone/chorionic gonadotropin receptor (PMID:8626439). It exists as multiple splice isoforms with distinct properties: GRK4alpha is uniquely inhibited by direct Ca2+/calmodulin binding (IC50 ~80 nM), whereas the beta, gamma, and delta isoforms do not bind calmodulin, and the isoforms differ in tissue distribution between testis and renal outer medulla (PMID:9092566, PMID:9607785). Across neuronal systems GRK4 desensitizes the mGlu1 metabotropic glutamate receptor in Purkinje cells via kinase-dependent phosphorylation (PMID:11099476) and the heterodimeric GABA(B) receptor through a phosphorylation-independent mechanism requiring direct complex formation with the GB2 subunit and agonist-triggered translocation to the plasma membrane (PMID:12881416, PMID:17013811). In the kidney, GRK4 acts as a central regulator of sodium handling by phosphorylating and uncoupling natriuretic receptors—dopamine D3R, adiponectin receptor-1, endothelin receptor type B, and the gastrin receptor CCKBR—from their G proteins, thereby impairing sodium excretion (PMID:19520868, PMID:32940654, PMID:32687659, PMID:37641972). GRK4 simultaneously enhances pressor signaling: it interacts with AT1R, and the hyperactive GRK4gamma A142V variant increases AT1R expression through the NF-kappaB pathway to potentiate angiotensin II-mediated vasoconstriction (PMID:24218433). GRK4 expression is itself controlled transcriptionally by c-Myc downstream of AT1R signaling, which uncouples D1R from adenylyl cyclase, and post-transcriptionally repressed by FMRP binding to GRK4 mRNA in cerebellum (PMID:23509080, PMID:26250109). Beyond receptor desensitization, GRK4 phosphorylates non-receptor substrates including TPI1 and Nedd4L to drive renal oxidative stress and ENaC-dependent sodium reabsorption (PMID:41407053), and in cardiomyocytes it phosphorylates M3-mAChR to disrupt its association with connexin43, increasing post-infarction arrhythmia susceptibility (PMID:40484036).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Establishing whether GRK4 is a catalytically functional receptor kinase and how it is membrane-targeted defined its basic biochemical identity.

    Evidence In vitro kinase assay against purified beta2-adrenergic receptor, [3H]palmitate labeling of all four splice variants, and receptor desensitization upon coexpression in HEK293 cells

    PMID:8626439

    Open questions at the time
    • Physiological substrates beyond model receptors not yet identified
    • Functional consequence of palmitoylation for localization untested
  2. 1997 High

    Determining isoform-specific catalytic and regulatory differences explained why GRK4 splice variants behave differently, particularly the unique Ca2+/calmodulin inhibition of GRK4alpha.

    Evidence Rhodopsin phosphorylation assays comparing isoforms, CaM-Sepharose pulldown, and ultrastructural localization in spermatozoa

    PMID:9092566

    Open questions at the time
    • Physiological role of calmodulin inhibition in sperm or other tissues unclear
    • Structural basis of GRK4alpha-specific calmodulin binding not resolved
  3. 1998 Medium

    Mapping isoform tissue distribution placed GRK4 catalytic activity in defined cellular contexts (spermatocytes vs renal outer medulla).

    Evidence Rhodopsin phosphorylation assay, in situ hybridization, and quantitative RT-PCR in rat tissues

    PMID:9607785

    Open questions at the time
    • Functional substrate in each tissue not identified
    • Human isoform distribution may differ from rat
  4. 2000 High

    Identifying mGlu1 as a GRK4 substrate in Purkinje cells demonstrated a kinase-dependent physiological desensitization role in neurons.

    Evidence Phosphorylation assay, antisense knockdown in primary Purkinje cells with desensitization rescue, and confocal colocalization upon agonist exposure

    PMID:11099476

    Open questions at the time
    • Phosphorylation sites on mGlu1 not mapped
    • Isoform responsible not defined
  5. 2003 High

    Discovery of phosphorylation-independent GABA(B) desensitization revealed that GRK4 can act as a scaffold/adaptor, not only a kinase.

    Evidence siRNA knockdown in cerebellar granule cells with transfection rescue and kinase-domain-deleted mutants retaining activity

    PMID:12881416

    Open questions at the time
    • Mechanism of kinase-independent desensitization not defined at the molecular level
    • Domain mediating effect not pinpointed in this study
  6. 2004 Medium

    Showing GRK4 does not bind Galphaq distinguished its regulatory repertoire from GRK2, clarifying which signaling modules it does not intercept.

    Evidence In vitro binding and cell-based Galphaq signaling assays using GRK N-terminal constructs

    PMID:15488187

    Open questions at the time
    • Negative result; other G protein interactions not surveyed
  7. 2007 High

    Resolving the direct GRK4-GB2 complex and agonist-triggered membrane translocation provided the physical basis for the earlier phosphorylation-independent GABA(B) effect.

    Evidence Reciprocal FRET and co-IP, live-cell translocation imaging, and Xenopus oocyte electrophysiology

    PMID:17013811

    Open questions at the time
    • Structural interface of GRK4-GB2 not determined
    • Trigger for cytosol-to-membrane translocation not defined
  8. 2009 High

    Linking GRK4 to dopamine D3R desensitization in renal proximal tubule established its role in the dopaminergic control of sodium handling.

    Evidence Reciprocal co-IP, BiFC interaction, RNAi knockdown with signaling/mitogenesis readouts, and isoform-specific phosphorylation in human RPT cells and rat kidney

    PMID:19520868

    Open questions at the time
    • D3R phosphorylation sites not mapped
    • Relative in vivo contribution of GRK4-gamma vs -alpha unclear
  9. 2013 High

    Defining the AT1R axis and c-Myc transcriptional control showed GRK4 both responds to and amplifies pressor signaling, mechanistically connecting GRK4 variants to hypertension.

    Evidence Co-IP, NF-kappaB ChIP/reporter, GRK4gamma 142V transgenic mice, calcium imaging, and ChIP for c-Myc at the GRK4 promoter with pharmacological rescue

    PMID:23509080 PMID:24218433

    Open questions at the time
    • Whether variant effects on AT1R are kinase-dependent not fully resolved
    • Human genetic causality not established by these mechanistic studies
  10. 2015 Medium

    Identifying FMRP-mediated translational repression and agonist-independent phosphorylation by the GRK4 subfamily expanded the regulatory and catalytic understanding of GRK4.

    Evidence In vitro/in vivo RNA binding (RIP) and Fmr1-null cerebellum protein/mRNA discordance; in vitro phosphorylation of inactive receptors using GRK5/6 as subfamily proxies

    PMID:25770216 PMID:26250109

    Open questions at the time
    • GRK4 itself not directly tested for inactive-receptor phosphorylation
    • Physiological relevance of FMRP repression outside cerebellum unknown
  11. 2023 Medium

    Extending GRK4 desensitization to AdipoR1, ETBR, CCKBR, and skeletal-muscle D1R generalized its role across natriuretic and metabolic receptors.

    Evidence Co-IP and confocal colocalization, GRK4 transgenic and siRNA/AAV knockdown models, Na+-K+-ATPase activity assays, and metabolic tolerance tests

    PMID:32687659 PMID:32940654 PMID:37622333 PMID:37641972

    Open questions at the time
    • Receptor phosphorylation sites largely unmapped
    • Most evidence from a single lab's transgenic models
  12. 2025 Medium

    Discovery of non-receptor substrates (TPI1, Nedd4L) and the cardiac M3-mAChR/Cx43 axis broadened GRK4 function beyond GPCR desensitization into metabolic, ion-transport, and arrhythmic mechanisms.

    Evidence IP-MS, co-IP, transgenic/knockdown mouse and cardiomyocyte models, H3K27ac ChIP, ENaC ubiquitination assays, and arrhythmia susceptibility testing

    PMID:40484036 PMID:41351606 PMID:41407053

    Open questions at the time
    • Direct phosphorylation of TPI1/Nedd4L/M3-mAChR sites needs mapping
    • Nedd4L finding is low-confidence and single-lab
    • Generalizability beyond disease models untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GRK4 isoform selection, palmitoylation, and translocation are coordinated to choose between kinase-dependent and kinase-independent desensitization across its many receptor and non-receptor substrates remains unresolved.
  • No structural model of GRK4 with any substrate
  • Determinants of substrate selectivity among isoforms unknown
  • In vivo phosphosite maps for most substrates absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0016740 transferase activity 4 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-382551 Transport of small molecules 4
Partners
ADIPOR1AGTR1CCKBRCHRM3DRD3EDNRBGB2 (GABBR2)NEDD4L

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 GRK4 is a functional protein kinase capable of phosphorylating agonist-occupied, purified beta2-adrenergic receptor in vitro, and all four splice variants incorporate [3H]palmitate (palmitoylation). GRK4 augments desensitization of the rat luteinizing hormone/chorionic gonadotropin receptor upon coexpression in HEK293 cells. In vitro kinase assay with purified beta2-adrenergic receptor; [3H]palmitate incorporation; coexpression in HEK293 cells with functional desensitization readout The Journal of biological chemistry High 8626439
1997 GRK4alpha, but not GRK4beta, -gamma, or -delta, phosphorylates rhodopsin in an agonist-dependent manner. GRK4alpha kinase activity is inhibited by Ca2+/calmodulin (IC50 ~80 nM) via a direct interaction; the other three isoforms do not interact with calmodulin. GRK4gamma is the only detectable isoform in human sperm. GRK4 is localized to acrosomal membranes and outer mitochondrial membranes of spermatozoa. Rhodopsin phosphorylation assay; CaM-Sepharose 4B pulldown; immunochemical and ultrastructural (electron microscopy) localization The Journal of biological chemistry High 9092566
1998 Rat GRK4A and GRK4B are both functional protein kinases, as demonstrated by rhodopsin phosphorylation. GRK4A mRNA predominates in leptotene to late pachytene primary spermatocytes and round spermatids; GRK4B mRNA is enriched ~20-fold in renal outer medulla compared to testis, indicating isoform-specific tissue distribution. Rhodopsin phosphorylation assay; in situ hybridization; quantitative RT-PCR Endocrinology Medium 9607785
1998 GRK4 delta (but not GRK2) did not significantly facilitate sequestration of muscarinic m1–m5 receptors in COS-7 cells, with the partial exception that GRK4 delta tended to facilitate m2 receptor sequestration. In BHK-21 cells, GRK4 delta facilitated sequestration of m2 but not m3 receptors. Radioligand binding ([3H]N-methylscopolamine) sequestration assay in COS-7 and BHK-21 cells with GRK coexpression The Journal of pharmacology and experimental therapeutics Medium 9495886
2000 GRK4 mediates homologous desensitization of the mGlu1 metabotropic glutamate receptor in cerebellar Purkinje cells. GRK4 kinase activity is required: agonist-dependent phosphorylation of mGlu1a was demonstrated, and antisense reduction of GRK4 in Purkinje cells impaired receptor desensitization. GRK4 redistributes and colocalizes with mGlu1 receptor upon agonist exposure and internalization. Coexpression in HEK293 cells with functional signaling assay; receptor phosphorylation assay; antisense knockdown in primary Purkinje cells; confocal colocalization imaging FASEB journal High 11099476
2003 GRK4 mediates agonist-promoted desensitization of the heterodimeric GABA(B) receptor in cerebellar granule cells via a phosphorylation-independent mechanism. siRNA knockdown of GRK4 strongly inhibited desensitization; GRK4 mutants deleted of their kinase domain could still promote desensitization; no ligand-induced receptor phosphorylation was detected. siRNA knockdown in cerebellar granule cells; transfection of kinase-dead/domain-deleted GRK4 mutants in HEK293 cells; functional desensitization assay The EMBO journal High 12881416
2004 GRK4, unlike GRK2, does not interact with Galphaq (neither in vitro nor in cells) and therefore does not inhibit Galphaq-dependent signaling, distinguishing the modulatory activities of these two kinase subfamilies. In vitro binding assay; cell-based signaling assay measuring Galphaq-dependent activity with GRK N-terminal domain constructs Methods in enzymology Medium 15488187
2007 GRK4 desensitizes GABA(B) receptor-mediated signaling by forming a direct protein complex with the GB2 subunit at the plasma membrane. Upon GABA(B) receptor activation, GRK4 translocates from cytosol to plasma membrane. FRET analysis and co-immunoprecipitation confirmed GRK4–GB2R complex formation. GRK5 also forms this complex; GRK2, GRK3, and GRK6 do not. FRET (GRK4-Cerulean / GB2R-Venus); co-immunoprecipitation/Western blot; live-cell imaging of GRK4 translocation; Xenopus oocyte electrophysiology; BHK cell transfection Journal of cellular physiology High 17013811
2009 GRK4 (specifically GRK4-gamma and GRK4-alpha isoforms) co-immunoprecipitates and co-localizes with the dopamine D3 receptor in human proximal tubule cells and rat kidney. Agonist activation initiates GRK4–D3R interaction at the cell membrane and promotes it intracellularly. GRK4-gamma and GRK4-alpha mediate 3- and 2-fold increases in phosphorylation of agonist-activated D3R, respectively. GRK4 knockdown abolished D3R-stimulated p44/42 phosphorylation and mitogenesis. Co-immunoprecipitation; bimolecular fluorescence complementation (BiFC) + confocal microscopy; RNAi knockdown; kinase activity inhibition with heparin; receptor phosphorylation assay The Journal of biological chemistry High 19520868
2013 GRK4 interacts directly with the angiotensin II type 1 receptor (AT1R) in vascular smooth muscle cells. The GRK4gamma A142V variant increases AT1R mRNA and protein expression via the NF-κB pathway (with greater NF-κB binding to the AT1R promoter), decreases AT1R phosphorylation (reducing degradation), and enhances AT1R-mediated intracellular calcium responses and angiotensin II-mediated vasoconstriction in transgenic mice. Co-immunoprecipitation; heterologous expression of GRK4γ 142V in A10 cells; NF-κB reporter/ChIP assay; calcium imaging; transgenic mouse model; aortic vasoconstriction assay Hypertension High 24218433
2013 The transcription factor c-Myc binds the GRK4 promoter and positively regulates GRK4 protein expression in human renal proximal tubule cells. Angiotensin II (via AT1R) increases phospho-c-Myc and subsequently GRK4 expression, which then uncouples D1R from adenylyl cyclase. c-Myc inhibitor 10074-G5 or AT1R blockade with losartan restored D1R coupling. Chromatin immunoprecipitation (ChIP) for c-Myc at GRK4 promoter; pharmacological inhibition; Western blot for phospho-c-Myc and GRK4; adenylyl cyclase coupling assay Hypertension Medium 23509080
2015 FMRP (Fragile X Mental Retardation Protein) binds GRK4 mRNA via a specific stem-loop domain (G4RIF) in the 3' region through its C-terminal domain, and negatively regulates GRK4 translation in cerebellum. GRK4 protein (but not mRNA) is increased in Fmr1-null cerebellum, indicating translational repression. In vitro RNA binding assay; in vivo RIP (RNA immunoprecipitation); Western blot and qPCR in Fmr1 knockout mouse cerebellum; reporter assay with G4RIF domain Nucleic acids research Medium 26250109
2015 GRK4 subfamily members (GRK5/6, closely related to GRK4) phosphorylate inactive (unactivated) GPCRs, including beta2-adrenergic and M2 muscarinic receptors, in an agonist-independent manner, and this phosphorylation enhances arrestin recruitment. GRK4 subfamily differs from GRK2/3 subfamily in this respect. In vitro phosphorylation assay; arrestin recruitment assay; mutagenesis to exclude constitutive receptor activity; membrane-association controls The Journal of biological chemistry Medium 25770216
2020 GRK4 phosphorylates and desensitizes the adiponectin receptor-1 (AdipoR1) in renal proximal tubule cells, uncoupling it from Gαi and impairing adiponectin-mediated inhibition of Na+-K+-ATPase activity. GRK4 transgenic (hyperphosphorylating variant) mice replicate impaired adiponectin-mediated natriuresis; siRNA-mediated GRK4 knockdown in SHR restores adiponectin-mediated sodium excretion. GRK4 transgenic mouse model; siRNA knockdown by renal ultrasound-directed delivery; Na+-K+-ATPase activity assay; co-immunoprecipitation; point mutation of AdipoR1 phosphorylation site Clinical science Medium 32940654
2020 GRK4 co-localizes and co-immunoprecipitates with the endothelin receptor type B (ETBR) in renal proximal tubule cells. Hyperphosphorylation of ETBR by GRK4 (as in SHR or GRK4γ 142V transgenic mice) impairs ETBR-mediated natriuresis and diuresis. siRNA knockdown of GRK4 restores inhibitory ETBR effect on Na+-K+-ATPase activity in SHR RPT cells. Co-immunoprecipitation; confocal colocalization; transgenic mouse model (GRK4γ 142V); ultrasound-targeted siRNA delivery; Na+-K+-ATPase activity assay; receptor phosphorylation assay FASEB journal Medium 32687659
2023 GRK4 co-localizes and co-immunoprecipitates with the renal gastrin receptor (CCKBR) in renal proximal tubule cells. GRK4 phosphorylates CCKBR; siRNA-mediated GRK4 knockdown reduces CCKBR phosphorylation and restores gastrin-mediated inhibition of Na+-K+-ATPase activity in SHR RPT cells. Co-immunoprecipitation; laser confocal microscopy; siRNA knockdown; Na+-K+-ATPase activity assay; GRK4 A142V transgenic mice Clinical and experimental hypertension Medium 37641972
2023 GRK4 phosphorylates and desensitizes the dopamine D1 receptor (D1R) in skeletal muscle, contributing to insulin resistance. In T2DM mice, GRK4 expression is increased (via ROS/c-Myc pathway), D1R phosphorylation is elevated, and insulin sensitivity is impaired. GRK4 transgenic mice show higher D1R phosphorylation and lower insulin sensitivity; AAV9-shGRK4 knockdown increases insulin sensitivity. GRK4 transgenic mouse model; AAV9-shRNA knockdown; receptor phosphorylation assay; glucose/insulin tolerance tests; pharmacological D1R agonism/antagonism Clinical science Medium 37622333
2025 GRK4 binds to M3 muscarinic acetylcholine receptor (M3-mAChR), increases its phosphorylation, and thereby impedes the M3-mAChR/Cx43 association, leading to connexin43 (Cx43) downregulation and redistribution in cardiomyocytes, increasing susceptibility to ventricular arrhythmias after myocardial infarction. GRK4 mRNA stability is enhanced by METTL3-mediated m6A modification via YTHDF1, increasing GRK4 expression in ischemic hearts. siRNA/adenovirus overexpression of GRK4 in cardiomyocytes under hypoxia; co-immunoprecipitation (GRK4–M3-mAChR; M3-mAChR–Cx43); Western blot; in vivo arrhythmia susceptibility assay; m6A modification analysis Biochemical pharmacology Medium 40484036
2025 In high-salt-fed GRK4 R65L mice, GRK4 interacts with triosephosphate isomerase 1 (TPI1) (identified by immunoprecipitation-mass spectrometry), increasing TPI1 phosphorylation and nuclear translocation, which decreases DHAP levels and increases H3K27ac binding to the Hao2 promoter, elevating renal Hao2-mediated oxidative stress and causing salt-sensitive hypertension. Immunoprecipitation-mass spectrometry (GRK4–TPI1 interaction); GRK4 R65L transgenic and global overexpression mice; AAV9-mediated renal knockdown; H3K27ac ChIP; DHAP measurement; antioxidant rescue (tempol) Free radical biology & medicine Medium 41407053
2025 PM2.5 upregulates renal GRK4 expression via promoter hypomethylation. GRK4 interacts with and phosphorylates Nedd4L (ubiquitin ligase); phosphorylated Nedd4L reduces ENaC ubiquitination, leading to ENaC accumulation and increased sodium reabsorption. GRK4 knockdown attenuates this effect. Co-immunoprecipitation (GRK4–Nedd4L); Western blot; promoter methylation assay; lentiviral GRK4 overexpression/knockdown; ENaC ubiquitination assay Blood pressure Low 41351606
2025 Omentin-1 suppresses GRK4 expression via the ROS/c-Myc signaling pathway in the kidney; GRK4 overexpression abolishes omentin-1's antihypertensive effects, confirming GRK4 as a downstream mediator of the ROS/c-Myc/GRK4/AT1R axis in salt-sensitive hypertension. GRK4 overexpression rescue experiment; Western blot; DOCA-salt hypertensive rat model; pharmacological ROS manipulation Biochemical pharmacology Low 41161545

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants. The Journal of biological chemistry 160 8626439
2000 The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 115 11099476
2003 Phosphorylation-independent desensitization of GABA(B) receptor by GRK4. The EMBO journal 100 12881416
1997 G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells. The Journal of biological chemistry 80 9092566
2006 Mechanisms of disease: the role of GRK4 in the etiology of essential hypertension and salt sensitivity. Nature clinical practice. Nephrology 73 17066056
1999 The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation. The Journal of biological chemistry 70 10506199
2009 G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. The Journal of biological chemistry 55 19520868
2015 G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs). The Journal of biological chemistry 51 25770216
2008 Blood pressure and renal sodium handling in relation to genetic variation in the DRD1 promoter and GRK4. Hypertension (Dallas, Tex. : 1979) 50 18413491
1998 Rat G protein-coupled receptor kinase GRK4: identification, functional expression, and differential tissue distribution of two splice variants. Endocrinology 48 9607785
1998 Sequestration of human muscarinic acetylcholine receptor hm1-hm5 subtypes: effect of G protein-coupled receptor kinases GRK2, GRK4, GRK5 and GRK6. The Journal of pharmacology and experimental therapeutics 44 9495886
2013 Role of GRK4 in the regulation of arterial AT1 receptor in hypertension. Hypertension (Dallas, Tex. : 1979) 41 24218433
2006 Patterns of genetic variation in the hypertension candidate gene GRK4: ethnic variation and haplotype structure. Annals of human genetics 41 16441255
2012 Abnormalities in renal dopamine signaling and hypertension: the role of GRK4. Current opinion in nephrology and hypertension 38 22123211
2007 Desensitization of GABA(B) receptor signaling by formation of protein complexes of GABA(B2) subunit with GRK4 or GRK5. Journal of cellular physiology 32 17013811
2015 The importance of G protein-coupled receptor kinase 4 (GRK4) in pathogenesis of salt sensitivity, salt sensitive hypertension and response to antihypertensive treatment. International journal of molecular sciences 27 25775155
2012 Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk. International journal of medical sciences 21 22639547
2015 The FMRP/GRK4 mRNA interaction uncovers a new mode of binding of the Fragile X mental retardation protein in cerebellum. Nucleic acids research 20 26250109
2015 Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis. Clinical interventions in aging 18 26730182
2020 GRK4-mediated adiponectin receptor-1 phosphorylative desensitization as a novel mechanism of reduced renal sodium excretion in hypertension. Clinical science (London, England : 1979) 17 32940654
2022 Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics. Pharmacology & therapeutics 16 35487286
2013 A novel role for c-Myc in G protein-coupled receptor kinase 4 (GRK4) transcriptional regulation in human kidney proximal tubule cells. Hypertension (Dallas, Tex. : 1979) 13 23509080
2020 Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population. Journal of diabetes and its complications 12 33127268
2020 Role of GRK4 in the regulation of the renal ETB receptor in hypertension. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 32687659
2022 LncRNA 148400 Promotes the Apoptosis of Renal Tubular Epithelial Cells in Ischemic AKI by Targeting the miR-10b-3p/GRK4 Axis. Cells 9 36552750
2024 Exosomal miR-122-3p represses the growth and metastasis of MCF-7/ADR cells by targeting GRK4-mediated activation of the Wnt/β-catenin pathway. Cellular signalling 7 38365112
2023 Dopamine Receptor D1R and D3R and GRK4 Interaction in Hypertension. The Yale journal of biology and medicine 7 37009199
2004 Analysis of differential modulatory activities of GRK2 and GRK4 on Galphaq-coupled receptor signaling. Methods in enzymology 7 15488187
2023 Exercise ameliorates skeletal muscle insulin resistance by modulating GRK4-mediated D1R expression. Clinical science (London, England : 1979) 5 37622333
2021 Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients. Clinical and experimental hypertension (New York, N.Y. : 1993) 5 33899625
2022 GRK4, A Potential Link between Hypertension and Breast Cancer. Journal of cell science & therapy 3 37994311
2021 Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang. PloS one 3 34297769
2023 Effect of GRK4 on renal gastrin receptor regulation in hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993) 2 37641972
2025 Inhibition of GRK4 reduces arrhythmia susceptibility and alleviates connexin43 dysregulation after myocardial infarction. Biochemical pharmacology 1 40484036
2024 Chronic exercise improves renal AT1 and ETB receptor functions via modulating GRK4 expression in obese Zucker rats. Clinical and experimental hypertension (New York, N.Y. : 1993) 1 38471134
2024 A cross-tissue transcriptome-wide association study reveals GRK4 as a novel susceptibility gene for COPD. Scientific reports 1 39558015
2025 Omentin-1 attenuates salt-sensitive hypertension via GRK4/AT1R downregulation mediated by the ROS/c-Myc pathway. Biochemical pharmacology 0 41161545
2025 PM2.5-induced hypertension via renal GRK4/Nedd4L/ENaC axis: epigenetic and post-translational mechanisms. Blood pressure 0 41351606
2025 GRK4 R65L causes salt-sensitive hypertension by augmenting renal Hao2-mediated oxidative stress via increasing the phosphorylation of TPI1 and promoting H3K27ac expression. Free radical biology & medicine 0 41407053

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