Affinage

GRK4

G protein-coupled receptor kinase 4 · UniProt P32298

Length
578 aa
Mass
66.6 kDa
Annotated
2026-04-28
39 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRK4 is a palmitoylated serine/threonine kinase of the GRK4 subfamily that phosphorylates and desensitizes a broad repertoire of G protein-coupled receptors—including dopamine D1R and D3R, mGlu1, GABA(B), LH/CG, ETB, CCKB, and M3-mAChR—as well as non-GPCR substrates such as adiponectin receptor-1, TPI1, and Nedd4L, thereby governing renal sodium handling, vascular tone, insulin sensitivity, and cardiac gap-junction integrity (PMID:8626439, PMID:11099476, PMID:19520868, PMID:32940654, PMID:41407053, PMID:40484036). The kinase exists as four splice isoforms whose activity is differentially regulated by Ca²⁺/calmodulin (which inhibits GRK4α but not β/γ/δ) and whose expression is transcriptionally driven by an angiotensin II→AT1R→c-Myc axis, while post-transcriptionally FMRP represses GRK4 translation in cerebellum and METTL3-mediated m⁶A modification stabilizes GRK4 mRNA in cardiomyocytes (PMID:9092566, PMID:23509080, PMID:26250109, PMID:40484036). Gain-of-function variants (R65L, A142V, A486V) confer constitutive receptor hyperphosphorylation in renal proximal tubule cells, impairing natriuresis and causing salt-sensitive hypertension in transgenic models (PMID:24218433, PMID:32687659, PMID:41407053). GRK4 can also desensitize GABA(B) receptors through a phosphorylation-independent mechanism that involves direct binding to the GB2 subunit (PMID:12881416, PMID:17013811).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Establishing GRK4 as a functional GPCR kinase resolved whether this testis-enriched gene encodes an active enzyme: all four splice variants phosphorylated agonist-occupied β2-adrenergic receptor, desensitized LH/CG receptor, and incorporated palmitate, placing GRK4 in the GRK family with a membrane-anchoring mechanism.

    Evidence In vitro kinase assay with purified β2AR; HEK293 coexpression desensitization; [³H]palmitate labeling

    PMID:8626439

    Open questions at the time
    • Endogenous substrates in testis not identified
    • Palmitoylation site(s) not mapped
    • Contribution to spermatogenesis unknown
  2. 1997 High

    Demonstrating that Ca²⁺/calmodulin selectively inhibits GRK4α (IC₅₀ ~80 nM) but not the other isoforms revealed an isoform-specific regulatory mechanism, while EM localization to sperm acrosomes and mitochondria defined the first subcellular address for endogenous GRK4.

    Evidence Rhodopsin phosphorylation with CaM titration; CaM-Sepharose pulldown; immunoEM of human spermatozoa

    PMID:9092566

    Open questions at the time
    • Calmodulin-binding site on GRK4α not mapped
    • Functional consequence of CaM regulation in spermatozoa not tested
  3. 2000 High

    Identifying mGlu1 as an endogenous GRK4 substrate in cerebellar Purkinje cells established GRK4 as a physiologically relevant kinase outside of testis, with antisense knockdown confirming a non-redundant role in mGlu1 desensitization.

    Evidence HEK293 desensitization/phosphorylation assays; confocal colocalization; antisense oligonucleotide knockdown in cultured Purkinje cells

    PMID:11099476

    Open questions at the time
    • Phosphorylation sites on mGlu1 not mapped
    • In vivo cerebellar phenotype of GRK4 loss not examined
  4. 2003 High

    Showing that GRK4 desensitizes GABA(B) receptor through a phosphorylation-independent mechanism expanded the paradigm beyond kinase activity, indicating GRK4 can function as a scaffolding partner for receptor regulation.

    Evidence Kinase-dead/deletion mutants retain desensitization; siRNA knockdown in cerebellar granule cells; HEK293 electrophysiology

    PMID:12881416

    Open questions at the time
    • Molecular basis of phosphorylation-independent desensitization (e.g., arrestin recruitment) not defined
    • Which GRK4 domain mediates the scaffolding function unknown
  5. 2007 High

    FRET and co-IP identification of a direct GRK4–GB2 subunit complex provided the physical basis for GABA(B) receptor desensitization and showed specificity within the GRK family (GRK2/3/6 did not form this complex).

    Evidence FRET (Cerulean/Venus fusions); co-immunoprecipitation; translocation imaging in BHK cells; Xenopus oocyte electrophysiology

    PMID:17013811

    Open questions at the time
    • GB2 binding interface on GRK4 not mapped
    • Whether GB2 interaction is phosphorylation-dependent or -independent not resolved
  6. 2009 High

    Demonstrating that GRK4γ and GRK4α phosphorylate dopamine D3R in renal proximal tubule cells, with knockdown abolishing D3R-mediated ERK signaling, linked GRK4 to renal dopaminergic signaling and natriuretic regulation.

    Evidence BiFC; co-IP; receptor phosphorylation assay; RNAi in human renal proximal tubule cells

    PMID:19520868

    Open questions at the time
    • D3R phosphorylation sites by GRK4 not mapped
    • In vivo renal D3R desensitization phenotype not tested
  7. 2013 High

    Two parallel studies revealed that GRK4 expression is transcriptionally controlled by angiotensin II→AT1R→c-Myc signaling, and that the gain-of-function GRK4γ 142V variant reciprocally upregulates AT1R via NF-κB, establishing a positive feedback loop in hypertension pathogenesis.

    Evidence ChIP for c-Myc on GRK4 promoter; c-Myc inhibitor; losartan; NF-κB reporter; GRK4γ 142V transgenic mice with vasoconstriction and calcium assays

    PMID:23509080 PMID:24218433

    Open questions at the time
    • Relative contribution of c-Myc versus other transcription factors not quantified
    • Whether AT1R upregulation by 142V occurs in human kidneys not confirmed
  8. 2015 High

    Discovery that FMRP directly binds a G4RIF structural element in GRK4 mRNA and represses its translation connected GRK4 to fragile X syndrome biology and explained elevated GRK4 protein in Fmr1-null cerebellum.

    Evidence In vitro FMRP–RNA binding; RNA structure analysis; Fmr1-KO mouse cerebellum Western/qRT-PCR; reporter translation assay

    PMID:26250109

    Open questions at the time
    • Whether elevated GRK4 protein causes specific GABA(B) or mGlu1 dysfunction in Fmr1-KO not tested
    • Other translational regulators of GRK4 not examined
  9. 2020 High

    Extending GRK4 substrates beyond GPCRs, two studies showed that GRK4 hyperphosphorylates adiponectin receptor-1 and endothelin ETB receptor in hypertensive rat kidneys, with in vivo GRK4 siRNA restoring natriuresis and lowering blood pressure, establishing GRK4 as a master desensitizer of multiple renal antinatriuretic pathways.

    Evidence Co-IP; GRK4γ 142V transgenic mice; renal-targeted siRNA via ultrasound microbubble destruction; Na⁺-K⁺-ATPase activity; natriuresis assays

    PMID:32687659 PMID:32940654

    Open questions at the time
    • Phosphorylation sites on AdipoR1 and ETBR not mapped
    • Whether GRK4 simultaneously targets all these receptors in the same cell not determined
  10. 2023 High

    Identification of CCKBR as another GRK4 renal substrate and demonstration that a ROS/c-Myc/GRK4 axis impairs D1R-mediated insulin sensitivity in skeletal muscle broadened GRK4 function to metabolic regulation beyond kidney.

    Evidence Co-IP (GRK4–CCKBR); GRK4 transgenic and AAV9-shGRK4 mice; glucose/insulin tolerance tests; c-Myc ChIP in skeletal muscle

    PMID:37622333 PMID:37641972

    Open questions at the time
    • Whether GRK4 directly phosphorylates CCKBR intracellular domains not confirmed with site mutagenesis
    • Skeletal muscle-specific GRK4 knockout not performed
  11. 2025 Medium

    Three recent studies expanded the GRK4 substrate repertoire to non-receptor targets: GRK4 phosphorylates TPI1 (promoting its nuclear translocation and epigenetic upregulation of Hao2 in salt-sensitive hypertension), binds M3-mAChR to disrupt Cx43-mediated gap junctions and promote post-MI arrhythmia (with GRK4 stability itself controlled by METTL3/m⁶A/YTHDF1), and phosphorylates Nedd4L to stabilize ENaC and cause sodium retention under PM2.5 exposure.

    Evidence IP-MS (GRK4–TPI1); GRK4 R65L transgenic mice; H3K27ac ChIP; co-IP (GRK4–M3-mAChR, GRK4–Nedd4L); m⁶A-RIP; in vivo arrhythmia and blood pressure assays

    PMID:40484036 PMID:41351606 PMID:41407053

    Open questions at the time
    • TPI1 phosphorylation site(s) and direct kinase assay not reported
    • M3-mAChR and Nedd4L findings each from a single lab, awaiting independent replication
    • Structural basis for GRK4 recognition of non-GPCR substrates entirely unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for GRK4's broad substrate promiscuity across GPCRs and non-GPCR targets, the phosphorylation-independent desensitization mechanism for GABA(B) receptor, identification of phosphorylation sites on most reported substrates, and whether a GRK4 knockout mouse recapitulates the predicted hypotensive/salt-resistant phenotype.
  • No crystal structure of GRK4 or GRK4–substrate complex
  • Full GRK4 knockout mouse phenotype not reported in the literature
  • Phosphorylation sites mapped on very few substrates

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-112316 Neuronal System 4 R-HSA-382551 Transport of small molecules 3
Partners
ADIPOR1AGTR1DRD1DRD3EDNRBGABBR2GRM1TPI1

Evidence

Reading pass · 20 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 β2-adrenergic receptor in vitro, augmenting desensitization of the rat LH/CG receptor upon coexpression in HEK293 cells, and all four splice variants incorporate [3H]palmitate (palmitoylation). In vitro phosphorylation assay with purified β2-adrenergic receptor; coexpression desensitization assay in HEK293 cells; [3H]palmitate metabolic labeling The Journal of biological chemistry High 8626439
1997 GRK4α, but not the β, γ, or δ isoforms, phosphorylates rhodopsin in an agonist-dependent manner; GRK4α kinase activity is inhibited by Ca²⁺/calmodulin (IC50 ~80 nM) through direct interaction, while the other isoforms do not interact with calmodulin. GRK4 protein localizes to acrosomal and outer mitochondrial membranes of human spermatozoa, with GRK4γ being the only detectable isoform in sperm. Rhodopsin phosphorylation assay; CaM-Sepharose pulldown; immunochemistry and ultrastructural (EM) localization in sperm The Journal of biological chemistry High 9092566
1998 Rat GRK4A and GRK4B are both functional protein kinases demonstrated by rhodopsin phosphorylation; GRK4A mRNA is enriched in testicular spermatocytes/spermatids whereas GRK4B is enriched ~20-fold in renal outer medulla, indicating isoform-specific tissue distribution with distinct physiological functions. Rhodopsin phosphorylation assay; in situ hybridization; quantitative RT-PCR Endocrinology High 9607785
1998 GRK4δ facilitates sequestration of muscarinic m2 (and to a lesser extent m4) receptors in BHK-21 cells but not in COS-7 cells, indicating cell-type-dependent modulation of muscarinic receptor internalization. Receptor sequestration assay (loss of [3H]NMS surface binding) with GRK4δ coexpression in COS-7 and BHK-21 cells The Journal of pharmacology and experimental therapeutics Medium 9495886
2000 GRK4 mediates homologous desensitization of the metabotropic glutamate receptor mGlu1 in cerebellar Purkinje cells: GRK4 coexpression in HEK293 cells caused agonist-dependent mGlu1 desensitization, agonist stimulation induced GRK4 redistribution and colocalization with internalized receptor, kinase activity was required, and agonist-dependent phosphorylation of mGlu1 was demonstrated. Antisense reduction of GRK4 in Purkinje cells impaired mGlu1 desensitization. Coexpression desensitization assay in HEK293; receptor phosphorylation assay; confocal colocalization; antisense knockdown in cultured Purkinje cells FASEB journal High 11099476
2003 GRK4 mediates agonist-promoted desensitization of the heterodimeric GABA(B) receptor in cerebellar granule cells through a phosphorylation-independent mechanism: GRK4 kinase-domain deletion mutants still promoted desensitization, siRNA knockdown of GRK4 in granule cells blocked desensitization, and GRK4 transfection into HEK293 cells reconstituted desensitization without detectable ligand-induced receptor phosphorylation. siRNA knockdown in cerebellar granule cells; kinase-dead/deletion mutant transfection; electrophysiological desensitization assay in HEK293 cells The EMBO journal High 12881416
2004 Unlike GRK2, the N-terminal RGS-like domain of GRK4 does not interact with Gαq either in vitro or in cells and cannot inhibit Gαq-dependent signaling, establishing that GRK4 lacks functional Gαq interaction. In vitro Gαq binding assay; cell-based signaling assay comparing GRK2 and GRK4 N-terminal domains Methods in enzymology Medium 15488187
2007 GRK4 desensitizes GABA(B) receptor by forming a direct protein complex with the GB2 subunit: agonist stimulation translocated cytosolic GRK4 to the plasma membrane, and FRET analysis (GRK4-Cerulean/GB2R-Venus) plus co-immunoprecipitation confirmed a physical GRK4–GB2R complex. GRK5 also formed this complex but GRK2, GRK3, and GRK6 did not. FRET (fluorescent fusion proteins); co-immunoprecipitation; live-cell translocation imaging in BHK cells; Xenopus oocyte electrophysiology Journal of cellular physiology High 17013811
2009 GRK4 (specifically GRK4γ and GRK4α isoforms) directly interacts with and phosphorylates the agonist-activated dopamine D3 receptor: bimolecular fluorescence complementation showed agonist-dependent GRK4–D3R interaction at the membrane and intracellularly; GRK4γ and α isoforms caused 3- and 2-fold increases in D3R phosphorylation, respectively; GRK4 knockdown abolished D3R-mediated p44/42 phosphorylation and mitogenesis. Bimolecular fluorescence complementation (BiFC); co-immunoprecipitation; receptor phosphorylation assay; RNAi knockdown with signaling readout in human proximal tubule cells The Journal of biological chemistry High 19520868
2013 GRK4γ directly interacts with angiotensin II type 1 receptor (AT1R); the gain-of-function variant GRK4γ 142V increases AT1R protein expression via NF-κB-mediated transcriptional upregulation, decreases AT1R phosphorylation (reducing degradation), and augments AT1R-mediated calcium signaling. The interaction between GRK4γ and AT1R is decreased by the 142V variant. Co-immunoprecipitation; NF-κB luciferase reporter; chromatin immunoprecipitation; calcium imaging; GRK4γ 142V transgenic mice with aortic vasoconstriction assay Hypertension High 24218433
2013 c-Myc transcription factor binds to the GRK4 promoter and positively regulates GRK4 expression in human renal proximal tubule cells; angiotensin II (via AT1R) activates c-Myc phosphorylation, which in turn increases GRK4 expression and causes dopamine D1 receptor uncoupling from adenylyl cyclase. Chromatin immunoprecipitation; c-Myc inhibitor (10074-G5); AT1R blockade with losartan; adenylyl cyclase coupling assay Hypertension High 23509080
2015 FMRP (fragile X mental retardation protein) binds directly to a structured domain (G4RIF) in GRK4 mRNA via its C-terminal region, repressing GRK4 translation in cerebellar Purkinje cells; in Fmr1-null cerebellum, GRK4 protein is increased without change in mRNA, indicating translational repression by FMRP. In vitro FMRP–mRNA binding assay; RNA secondary structure analysis; Western blot and qRT-PCR in Fmr1-null cerebellum; reporter translational repression assay Nucleic acids research High 26250109
2015 GRK4 subfamily members (GRK5 and GRK6, but not GRK2/3) phosphorylate inactive (non-agonist-occupied) GPCRs including β2-adrenergic and M2 muscarinic receptors; this agonist-independent phosphorylation enhances arrestin recruitment to inactive receptors, and arrestin-3 discriminates between GRK2- and GRK5-mediated phosphorylation patterns. In vitro phosphorylation assay with inactive receptors; arrestin recruitment assay; constitutive activity controls; membrane association controls The Journal of biological chemistry High 25770216
2020 GRK4 directly interacts with and hyperphosphorylates the adiponectin receptor-1 (AdipoR1) in renal proximal tubule cells from spontaneously hypertensive rats (SHRs), uncoupling AdipoR1 from Gαi and impairing adiponectin-mediated inhibition of Na⁺-K⁺-ATPase; GRK4γ 142V transgenic mice replicate this phenotype, and siRNA-mediated GRK4 knockdown in vivo restores adiponectin-induced natriuresis and reduces blood pressure. Co-immunoprecipitation; point mutation abolishing receptor phosphorylation; GRK4γ 142V transgenic mice; renal siRNA knockdown via ultrasound-targeted microbubble destruction; Na⁺-K⁺-ATPase activity assay Clinical science High 32940654
2020 GRK4 co-localizes and co-immunoprecipitates with the endothelin ETB receptor in renal proximal tubule cells; in SHRs and GRK4γ 142V transgenic mice, ETBR is hyperphosphorylated by GRK4, impairing ETBR-mediated natriuresis and diuresis; siRNA knockdown or in vivo GRK4 reduction restores ETBR function. Co-immunoprecipitation; confocal colocalization; GRK4γ 142V transgenic mice; siRNA knockdown via ultrasound-targeted microbubble destruction; in vivo natriuresis assay FASEB journal High 32687659
2023 GRK4 phosphorylates the cholecystokinin B receptor (CCKBR/gastrin receptor) in renal proximal tubule cells; GRK4 and CCKBR co-localize and co-immunoprecipitate; GRK4 siRNA reduces CCKBR phosphorylation and restores gastrin-mediated inhibition of Na⁺-K⁺-ATPase activity in SHR cells. Co-immunoprecipitation; confocal co-localization; siRNA knockdown; Na⁺-K⁺-ATPase activity assay; GRK4 A142V transgenic mice Clinical and experimental hypertension Medium 37641972
2023 GRK4-mediated phosphorylation of dopamine D1R in skeletal muscle is regulated upstream by a ROS/c-Myc pathway: in insulin-resistant/T2DM mice, increased ROS elevates c-Myc expression, which transcriptionally upregulates GRK4, leading to D1R hyperphosphorylation and impaired insulin sensitivity; exercise reverses this axis, and GRK4 transgenic mice show worsened D1R phosphorylation and insulin resistance while AAV9-shGRK4 mice are more insulin sensitive. GRK4 transgenic and AAV9-shGRK4 mice; glucose and insulin tolerance tests; D1R phosphorylation assay; c-Myc ChIP; ROS measurement Clinical science High 37622333
2025 GRK4 promotes arrhythmia after myocardial infarction by binding to and phosphorylating the M3 muscarinic acetylcholine receptor (M3-mAChR), which impedes M3-mAChR–Cx43 association, causing Cx43 downregulation and redistribution; GRK4 mRNA/protein stability is increased via METTL3-mediated m6A modification read by YTHDF1. GRK4 knockdown reduces Cx43 dysregulation and ventricular arrhythmia susceptibility. siRNA and adenoviral overexpression of GRK4 in cardiomyocytes; co-immunoprecipitation (GRK4–M3-mAChR; M3-mAChR–Cx43); m6A RNA methylation assay; METTL3/YTHDF1 interaction; in vivo arrhythmia susceptibility assay post-MI Biochemical pharmacology Medium 40484036
2025 GRK4 R65L variant causes salt-sensitive hypertension via phosphorylation of triosephosphate isomerase 1 (TPI1), which promotes TPI1 nuclear translocation, reduces DHAP levels, increases H3K27ac binding to the Hao2 promoter, and upregulates Hao2-mediated renal oxidative stress. Immunoprecipitation-mass spectrometry identified increased GRK4–TPI1 interaction in kidneys of high-salt-fed GRK4 R65L mice. GRK4 R65L global and renal-targeted transgenic mice; immunoprecipitation–mass spectrometry; TPI1 phosphorylation and nuclear fractionation; H3K27ac ChIP; Hao2 AAV9 knockdown; oxidative stress measurement; pressure-natriuresis assay Free radical biology & medicine Medium 41407053
2025 PM2.5 upregulates renal GRK4 expression via promoter hypomethylation; elevated GRK4 then phosphorylates and interacts with Nedd4L (a ubiquitin ligase), stabilizing Nedd4L phosphorylation; phospho-Nedd4L reduces ENaC ubiquitination, causing ENaC accumulation and sodium retention that drives hypertension. GRK4 overexpression exacerbated and knockdown attenuated these effects. Co-immunoprecipitation (GRK4–Nedd4L); methylation assay; lentiviral GRK4 overexpression/knockdown; ENaC ubiquitination assay; Western blot; in vivo blood pressure measurement Blood pressure Medium 41351606

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 50 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 37 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 25 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
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
2015 Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis. Clinical interventions in aging 17 26730182
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
2004 Analysis of differential modulatory activities of GRK2 and GRK4 on Galphaq-coupled receptor signaling. Methods in enzymology 7 15488187
2023 Dopamine Receptor D1R and D3R and GRK4 Interaction in Hypertension. The Yale journal of biology and medicine 6 37009199
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