Affinage

GRK5

G protein-coupled receptor kinase 5 · UniProt P34947

Length
590 aa
Mass
67.8 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRK5 is a membrane-associated serine/threonine kinase that phosphorylates agonist-occupied G protein-coupled receptors to initiate desensitization, and it doubles as a calcium-gated nuclear transcriptional regulator (PMID:8120045, PMID:8288567, PMID:25332207). Unlike β-adrenergic receptor kinase, GRK5 phosphorylates rhodopsin in a light-dependent manner, is not activated by Gβγ, lacks an isoprenylation site, and instead remains constitutively associated with the plasma membrane (PMID:7685906, PMID:8120045, PMID:8288567, PMID:18034461). Membrane targeting and full catalytic competence depend on a C-terminal amphipathic helix and on phospholipid-stimulated autophosphorylation at Ser484/Thr485, while a hydrophobic dimerization interface in the RGS homology domain further supports plasma membrane localization (PMID:8144599, PMID:14976207, PMID:24807909). GRK5 phosphorylates a broad panel of receptors—β2AR, m2 muscarinic, rhodopsin, neurotensin receptor 1, FPR2, CB1, and PAR1—forming a dynamic complex with agonist-occupied β2AR, and its receptor engagement controls desensitization, internalization, and the balance of β-arrestin-dependent signaling (PMID:8120045, PMID:8288567, PMID:26120872, PMID:28431242, PMID:39706266, PMID:24407588, PMID:41557909). Its activity is negatively tuned by PKC phosphorylation of the C-terminus and by N-terminal actin binding, and is gated by Ca2+/calmodulin, which binds independent helical regions at the N- and C-termini to simultaneously block receptor phosphorylation, disrupt membrane association, and drive nuclear translocation while activating phosphorylation of soluble substrates (PMID:9013639, PMID:9685424, PMID:31337679, PMID:33321095). In the nucleus GRK5 binds DNA directly via an NLS-containing region and acts in a kinase-independent manner as a co-activator of NFAT and NF-κB to drive pathological cardiac hypertrophic gene transcription and cardiac fibroblast activation (PMID:23658733, PMID:25332207, PMID:24174526, PMID:33500351). Beyond GPCRs, GRK5 phosphorylates moesin, the cardiac mineralocorticoid receptor, β-arrestin1, HDAC5, and HDAC6, linking it to cancer cell migration, mineralocorticoid receptor repression, and fibrotic and metabolic programs (PMID:24755472, PMID:32326036, PMID:19661922, PMID:37520700, PMID:38206179, PMID:39779910). A common GRK5 Q41L polymorphism enhances β-adrenergic desensitization and protects against catecholamine-induced cardiomyopathy (PMID:18425130).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1993 High

    Established GRK5 as a distinct GRK family member by showing it phosphorylates rhodopsin light-dependently without Gβγ activation or isoprenylation, distinguishing its membrane-targeting mechanism from βARK.

    Evidence Baculovirus/Sf9 overexpression with in vitro kinase assay and sequence analysis

    PMID:7685906

    Open questions at the time
    • Membrane-association mechanism not yet defined
    • Physiological GPCR substrates beyond rhodopsin not addressed
  2. 1994 High

    Defined GRK5 as a broad receptor kinase acting on β2AR, m2 muscarinic, and rhodopsin, mapped autophosphorylation to Ser484/Thr485, and showed constitutive membrane association rather than agonist-triggered translocation.

    Evidence Sf9 purification, in vitro kinase and autophosphorylation site mapping

    PMID:8120045 PMID:8288567

    Open questions at the time
    • Functional role of autophosphorylation not yet established
    • Membrane-targeting motif unidentified
  3. 1994 High

    Showed phospholipid-stimulated autophosphorylation at Ser484/Thr485 activates the kinase, linking lipid sensing to catalytic competence.

    Evidence In vitro kinase assay with S484A/T485A mutant and phospholipid binding

    PMID:8144599

    Open questions at the time
    • Structural basis of autophosphorylation across the catalytic cleft unknown
  4. 1997 High

    Identified PKC phosphorylation of the C-terminus as a negative regulatory input that lowers receptor phosphorylation and membrane binding without affecting phospholipid binding.

    Evidence In vitro PKC phosphorylation, intact-cell PMA treatment, kinetic and membrane-binding analysis

    PMID:9013639

    Open questions at the time
    • In vivo significance of PKC crosstalk not established
  5. 1998 High

    Revealed N-terminal actin binding as an inhibitory mechanism and calmodulin as a switch that displaces GRK5 from actin to permit soluble-substrate phosphorylation.

    Evidence In vitro binding/kinase assays with N-terminal mutagenesis and measured Kd values

    PMID:9685424

    Open questions at the time
    • Cellular consequence of actin/CaM switching not yet tested
  6. 2002 Medium

    First implicated nuclear GRK5 in disease by showing it accumulates in the nucleus of hypertensive heart-failure-prone cardiomyocytes, hinting at a non-receptor role.

    Evidence Subcellular fractionation and confocal co-localization in SHHF vs WKY myocytes

    PMID:12052842

    Open questions at the time
    • No functional consequence of nuclear localization tested
    • Single rat model, no causal manipulation
  7. 2004 High

    Identified a C-terminal amphipathic helix (aa 546–565) as the determinant of plasma membrane localization and lipid-dependent activity.

    Evidence GFP-fusion live-cell imaging with hydrophobic-residue mutagenesis and autophosphorylation assay

    PMID:14976207

    Open questions at the time
    • Whether other regions contribute to membrane binding not resolved
  8. 2007 Medium

    Established GRK5 as constitutively pre-associated with β2AR at the membrane and extended its desensitization role to GABA(B) receptors.

    Evidence BRET2/FRET co-localization, cell-free membrane phosphorylation, GRK immunodepletion, oocyte electrophysiology

    PMID:17013811 PMID:18034461

    Open questions at the time
    • Pre-coupling stoichiometry and dynamics not quantified
    • GABA(B) interaction not structurally defined
  9. 2008 High

    Linked a GRK5 coding polymorphism (Q41L) to enhanced β-adrenergic desensitization and cardioprotection, demonstrating physiological consequence of GRK5 activity variation.

    Evidence Transfected cell functional assays, transgenic mice, catecholamine challenge

    PMID:18425130

    Open questions at the time
    • Molecular mechanism of the L41 gain-of-function not fully defined
  10. 2009 High

    Expanded GRK5 substrate scope beyond receptors to β-arrestin1 (Ser412) and to selective regulation of presynaptic M2/M4 autoreceptor desensitization in neurons.

    Evidence Co-IP, phosphorylation/mutagenesis with ERK readout; GRK5 KO hippocampal slices with pharmacological rescue

    PMID:19478075 PMID:19661922

    Open questions at the time
    • Generality of β-arrestin1 phosphorylation across receptors unknown
    • Behavioral consequences of cholinergic deficit not addressed
  11. 2011 High

    Defined a kinase-independent cytoskeletal/membrane-remodeling function: GRK5 bundles F-actin and shapes neuronal dendrites and spines, with KO mice showing learning/memory deficits.

    Evidence Domain mutagenesis, in vitro actin bundling, live imaging, GRK5 KO mouse behavior/morphology

    PMID:21930777

    Open questions at the time
    • Relationship between actin function and nuclear/receptor functions unclear
  12. 2013 High

    Established the mechanistic basis of nuclear GRK5 action: an NLS/CaM-dependent DNA-binding region plus an NES enabling Ca2+/CaM-regulated nucleocytoplasmic shuttling, and direct upregulation of NF-κB transcription in cardiomyocytes.

    Evidence Chimera/mutagenesis, in vitro DNA binding, localization imaging; adenoviral/siRNA NF-κB reporter, EMSA, NLS mutant

    PMID:23658733 PMID:24174526

    Open questions at the time
    • DNA sequence specificity of GRK5 binding not defined
    • Direct NF-κB target genes not enumerated
  13. 2014 High

    Demonstrated nuclear GRK5 drives NFAT-dependent hypertrophic transcription via direct DNA binding without phosphorylation, with epistasis through NFATc3 establishing it as a transcriptional co-activator in heart disease.

    Evidence NFAT-luciferase, transgenic/KO mouse TAC, adenoviral transfer, NFATc3 KO epistasis

    PMID:25332207

    Open questions at the time
    • Whether GRK5 contacts NFAT directly or via shared DNA elements not fully resolved
  14. 2014 High

    Extended GRK5 kinase substrates to moesin (Thr66), linking it to cytoskeletal/focal-adhesion regulation and prostate cancer cell motility.

    Evidence MS phosphoproteomics, in vitro kinase, T66 mutagenesis, siRNA, xenograft

    PMID:24755472

    Open questions at the time
    • Upstream signal triggering moesin phosphorylation not defined
  15. 2014 Medium

    Showed RGS-domain dimerization (HDI region) supports membrane localization and PAR1-coupled calcium regulation, adding self-association to GRK5's membrane-targeting repertoire.

    Evidence Chimeras, point mutagenesis (M165E/F166E), co-IP, FRET, calcium release assay

    PMID:24807909

    Open questions at the time
    • Physiological prevalence and regulation of dimerization unknown
  16. 2014 High

    Established a GRK5-dependent, kinase-required CB1 receptor signaling route through β-arrestin to ERK and RGS4 phosphorylation controlling smooth muscle contraction.

    Evidence GRK5 K215R, β-arrestin siRNA epistasis, RGS4 site mutagenesis, contraction assay

    PMID:24407588

    Open questions at the time
    • Tissue generality of the CB1-GRK5-RGS4 axis untested
  17. 2015 High

    Provided structural and biochemical mechanisms: a 1.8 Å full-length structure explaining cis-autophosphorylation, and nanodisc reconstitution showing GRK5 phosphorylates NTSR1 activation-independently with lipid-dependent regiospecificity distinct from GRK2.

    Evidence X-ray crystallography; nanodisc in vitro phosphorylation with MS site mapping and NTSR1 mutants

    PMID:26032409 PMID:26120872

    Open questions at the time
    • Conformational changes during receptor engagement not captured by static structure
  18. 2017 High

    Defined the dynamic GRK5–β2AR engagement, mapping receptor contacts to the RH bundle, membrane-binding surface, and catalytic cleft and revealing large interdomain rearrangements.

    Evidence XL-MS, HDX-MS, EM, mutagenesis, MD simulations, docking

    PMID:28431242

    Open questions at the time
    • High-resolution receptor-bound structure still lacking
  19. 2019 High

    Clarified how Ca2+·CaM allosterically inhibits receptor phosphorylation while activating soluble-substrate phosphorylation, and showed a chemical probe (malbrancheamide) can block GRK5 nuclear translocation and hypertrophy.

    Evidence SAXS, negative-stain EM, natural-product probe, in-cell translocation and hypertrophy assays

    PMID:31337679

    Open questions at the time
    • Selectivity and in vivo efficacy of the probe not established
  20. 2020 High

    Resolved the CaM-GRK5 structure showing independent N- and C-domain engagement that separates membrane disruption (translocation) from kinase activation, unifying the calcium-gated localization switch.

    Evidence Cryo-EM/crystal structure, MD, kinase assays, localization experiments

    PMID:33321095

    Open questions at the time
    • In-cell kinetics of the CaM-driven switch under physiological calcium not measured
  21. 2020 Medium

    Extended GRK5 cardiac substrates and partners to the mineralocorticoid receptor (repression upon β2AR activation) and the β1AR-SAP97-CaMKII complex, broadening its cardiomyocyte signaling roles.

    Evidence CRISPR KO/overexpression, co-IP, MR reporter; cardiac-specific conditional KO with co-IP and CaMKII activity

    PMID:32326036 PMID:32507058

    Open questions at the time
    • MR phosphosites not mapped
    • Direct vs indirect effects on the β1AR-SAP97 complex unresolved
  22. 2021 High

    Demonstrated nuclear GRK5 drives cardiac fibroblast activation and that a CaM-binding peptide inhibitor (GRK5nt) blocks nuclear accumulation and pathological NFAT/NF-κB transcription, providing a therapeutic proof-of-concept.

    Evidence Fibroblast-specific KO with AngII/MI models; GRK5nt adenoviral/transgenic mice, TAC, CaM co-IP, reporters

    PMID:33500351 PMID:33785612

    Open questions at the time
    • Fibroblast nuclear GRK5 transcriptional targets not enumerated
    • GRK5nt pharmacokinetics/specificity untested
  23. 2022 High

    Refined receptor-level selectivity (Gq determines GRK2/3 vs GRK5/6 usage at AT1R) and revealed that catalytic activity is required for cardiac homeostasis, since catalytic-dead K215R mice develop dysfunction and fibrosis.

    Evidence GRK inhibition/KO with β-arrestin recruitment and single-molecule imaging; K215R knock-in mice with echocardiography/histology

    PMID:35078997 PMID:35540100

    Open questions at the time
    • How nuclear-restricted catalytic-dead GRK5 raises p53 mechanistically unclear
    • Generality of Gq-gated selectivity across receptors limited
  24. 2024 Medium

    Broadened GRK5's substrate/regulatory network to HDAC family kinases—HDAC6 in chondrocytes (downstream of KLF9) and HDAC5/Smad3 in renal fibrosis—and to FPR2 endocytic control, linking GRK5 to osteoarthritis, renal fibrosis, and trafficking.

    Evidence ChIP/luciferase, co-IP, phosphorylation and rescue assays (HDAC6); overexpression/knockdown with pathway Western and MEF2A reporter (HDAC5); GRK5/β-arrestin genetic dissection of FPR2 trafficking

    PMID:38206179 PMID:39706266 PMID:39779910

    Open questions at the time
    • Direct HDAC phosphosites not all mapped
    • Whether these are kinase-dependent or nuclear scaffolding roles partly unresolved
  25. 2025 Medium

    Connected GRK5 to CFTR rescue and refined its β-cell metabolic role, identifying GRK5 as a regulator of p.Phe508del-CFTR plasma membrane trafficking and of HDAC5/immediate-early-gene programs supporting β-cell mass.

    Evidence Genome-wide siRNA screen with CFTR functional validation; β-cell-specific Grk5 KO with GTT, β-cell mass, RNA-seq, HDAC5 phosphorylation

    PMID:37520700 PMID:40040803

    Open questions at the time
    • GRK5-CFTR mechanistic pathway undefined
    • Direct β-cell GRK5 substrate driving IEG program not pinned down
  26. 2026 High

    Established a clinically relevant GRK5 role in hemostasis: low platelet GRK5 (via rs10886430) impairs PAR1 desensitization, increasing thrombin responsiveness and thrombus formation.

    Evidence Human platelet quantification, PAR1 internalization/activation assays, microfluidics, GRK5 KO iPSC-megakaryocytes, Grk5-deficient mouse platelets, in vivo thrombosis

    PMID:41557909

    Open questions at the time
    • PAR1 phosphosites targeted by GRK5 in platelets not mapped
    • Selectivity over PAR4 mechanism not fully explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the membrane-receptor kinase, cytoskeletal, and nuclear DNA-binding/transcriptional functions of GRK5 are coordinately partitioned in a given cell, and the DNA sequence specificity of nuclear GRK5, remain unresolved.
  • No genome-wide map of nuclear GRK5 DNA occupancy
  • Quantitative rules governing receptor- vs nuclear-pool allocation unknown
  • Direct vs cofactor-mediated transcriptional contacts for NFAT/NF-κB undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0008289 lipid binding 3 GO:0016740 transferase activity 3 GO:0003677 DNA binding 2 GO:0008092 cytoskeletal protein binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-109582 Hemostasis 1
Partners
ACTBADRB2ARRB1CALM1HDAC5NR3C2PHLPP2SAP97

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 GRK5 phosphorylates rhodopsin in a light-dependent manner and is not activated by G-protein βγ subunits, unlike βARK, and does not contain a consensus sequence for isoprenylation, distinguishing it from other GRK family members. Baculovirus/Sf9 overexpression, in vitro kinase assay, sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 7685906
1994 Purified GRK5 phosphorylates β2-adrenergic receptor, m2 muscarinic receptor, and rhodopsin in an agonist/light-dependent manner; major autophosphorylation sites mapped to Ser484 and Thr485; GRK5 associates with membranes constitutively and does not translocate upon agonist stimulation. Sf9 purification, in vitro kinase assay, peptide phosphorylation, autophosphorylation site mapping The Journal of biological chemistry High 8120045 8288567
1994 Phospholipid-stimulated autophosphorylation of GRK5 at Ser484 and Thr485 (C-terminal region, aa 489–590 mediates phospholipid interaction) activates GRK5; a non-autophosphorylatable S484A/T485A mutant has ~15–20-fold reduced ability to phosphorylate β2AR and rhodopsin. In vitro kinase assay, mutagenesis (S484A/T485A), GST fusion-protein phospholipid binding, phosphoamino acid analysis The Journal of biological chemistry High 8144599
1997 PKC phosphorylates GRK5 at two major sites within the C-terminal 26 amino acids, stoichiometrically reducing its ability to phosphorylate rhodopsin (~5-fold increased Km, ~3-fold decreased Vmax) and decreasing its ability to bind rhodopsin-containing membranes, without altering direct phospholipid binding. In vitro PKC phosphorylation assay, intact-cell PMA treatment of COS-1 cells, kinetic analysis, membrane-binding assay The Journal of biological chemistry High 9013639
1998 Actin binds and inhibits GRK5: monomeric actin binds with Kd ~0.6 μM and filamentous actin with Kd ~0.2 μM; mutation of 6 N-terminal amino acids eliminates actin-mediated inhibition. Calmodulin (which binds the GRK5 N-terminus) displaces GRK5 from actin, selectively permitting phosphorylation of soluble but not membrane-bound GPCR substrates. In vitro binding assay, in vitro kinase assay, N-terminal mutagenesis The Journal of biological chemistry High 9685424
2004 A predicted amphipathic helix (aa 546–565) in the GRK5 C-terminus mediates plasma membrane localization; hydrophobic residues within this helix are necessary for PM targeting of GFP fusion constructs and for phospholipid-dependent autophosphorylation and phosphorylation of membrane-bound rhodopsin. GFP fusion live-cell imaging, mutagenesis of hydrophobic/basic residues, autophosphorylation assay The Journal of biological chemistry High 14976207
2007 GRK5 is constitutively associated with β2AR at the plasma membrane (demonstrated by high basal BRET2 between β2AR-Rluc and GRK5-GFP2 that is not diminished by agonist). Extensively washed plasma membranes retain GRK5 and support agonist-dependent GRK site phosphorylation (pS355/356) of β2AR, while GRK2 is depleted. BRET2 assay, cell-free membrane phosphorylation assay, immunodepletion of GRKs Biochemistry Medium 18034461
2008 GRK5-Leu41 (Q41L polymorphism) uncouples isoproterenol-stimulated β-adrenergic responses more effectively than GRK5-Gln41 in transfected cells and transgenic mice, providing enhanced βAR desensitization ('genetic beta-blockade') and protecting against catecholamine-induced cardiomyopathy. Transfected cell functional assay, transgenic mouse model, catecholamine challenge model Nature medicine High 18425130
2009 GRK5 phosphorylates β-arrestin1 at Ser412 when β-arrestin1 is bound to the phosphorylated 5-HT4 receptor C-terminus; this phosphorylated β-arrestin1 prevents activation of Src constitutively bound to the receptor, thereby inhibiting the G protein-independent Src/ERK signaling pathway. Co-immunoprecipitation, phosphorylation assay, site-directed mutagenesis, ERK activity measurement in HEK-293 cells and neurons The EMBO journal High 19661922
2011 GRK5 promotes F-actin bundling and targets bundles to plasma membrane structures via simultaneous interaction with F-actin and phosphatidylinositol-4,5-bisphosphate; separate domains of GRK5 mediate actin cytoskeleton coupling and membrane remodeling, and this function (not kinase activity) is required for neurite outgrowth, dendrite branching, and spine morphogenesis. GRK5 KO mice display immature spine morphology and deficient learning and memory. Domain deletion/mutagenesis, in vitro F-actin bundling assay, live-cell imaging, GRK5 KO mouse behavioral and morphological analysis The Journal of cell biology High 21930777
2002 In hypertensive heart failure-prone (SHHF) rat cardiomyocytes, GRK5 specifically accumulates in the nucleus (colocalizing with coilin, a component of nuclear substructures involved in RNA synthesis/processing), whereas in normal WKY myocytes it distributes diffusely in the cytoplasm. Subcellular fractionation, fluorescent confocal microscopy, co-localization with nuclear markers Hypertension Medium 12052842
2013 GRK5 contains a nuclear localization sequence (NLS) that also binds DNA in vitro; the DNA-binding ability requires both the NLS and an N-terminal calmodulin-binding site. A functional nuclear export sequence (NES) was identified that mediates Ca2+/CaM-dependent nuclear export. GRK5 nuclear localization is differentially regulated from GRK4 and GRK6 subfamily members. GRK5/GRK4/GRK6 chimera analysis, mutagenesis, in vitro DNA-binding assay, live-cell nuclear localization imaging PloS one Medium 23658733
2013 Nuclear GRK5 increases NF-κB p50 and p65 levels, promotes p65 phosphorylation, increases NF-κB DNA binding activity, and drives NF-κB reporter activity in cardiomyocytes; a nuclear-localization-deficient GRK5 mutant loses these effects, indicating dependence on nuclear translocation. Adenoviral overexpression, siRNA knockdown in NRVMs, NF-κB reporter assay, EMSA, co-immunoprecipitation, nuclear-localization mutant The Journal of biological chemistry High 24174526
2014 Nuclear GRK5 enhances NFAT-mediated hypertrophic gene transcription in cardiomyocytes via direct DNA binding (without a phosphorylation event); GRK5 transgenic mice show elevated NFAT reporter activity basally and after TAC/PE; GRK5 null mice have reduced NFAT activity after TAC; loss of NFATc3 protects GRK5-overexpressing mice from exaggerated hypertrophy. NFAT-luciferase reporter, transgenic and knockout mouse TAC model, adenoviral gene transfer, molecular DNA-binding studies, epistasis via NFATc3 KO Circulation research High 25332207
2014 GRK5 phosphorylates moesin at Thr66 (identified by mass spectrometry and confirmed by mutation), regulates moesin subcellular distribution, colocalizes with moesin at the cell periphery, and controls prostate cancer cell migration, invasion, and focal adhesion formation. Mass spectrometric phosphoproteome, in vitro kinase assay, T66 mutagenesis, co-localization imaging, GRK5 siRNA knockdown, xenograft model Cancer research High 24755472
2009 GRK5 deficiency selectively impairs desensitization of presynaptic M2/M4 muscarinic autoreceptors (not M1 receptors), causing reduced internalization of M2/M4 upon agonist treatment, leading to reduced hippocampal acetylcholine release that is correctable by M2/M4 antagonist methoctramine or pertussis toxin. Dominant-negative GRK5 overexpression in cholinergic cells, GRK5 KO hippocampal slices, ACh release measurement, receptor immunoreactivity assay, pharmacological rescue The Journal of biological chemistry High 19478075
2015 GRK5 and GRK2 differentially phosphorylate neurotensin receptor 1 (NTSR1): GRK2 phosphorylates only C-terminal Ser residues in an agonist-dependent manner, while GRK5 phosphorylates Ser/Thr in intracellular loop 3 and C-terminus in an activation-independent manner; negatively charged lipids in the immediate vicinity of NTSR1 directly affect phosphorylation by GRKs. Nanodisc reconstitution in vitro phosphorylation, mass spectrometry phosphosite mapping, NTSR1 mutant panel Biochemistry High 26120872
2015 Crystal structure of full-length human GRK5 at 1.8 Å resolution reveals that the C-terminal tail (AST segment) forms novel interactions with the nucleotide and N-lobe not previously observed in other GRKs; the NLT is displaced from positions seen in other GRKs; autophosphorylation sites in the NLT can undergo rapid cis-autophosphorylation despite being >20 Å from the catalytic cleft. X-ray crystallography (1.8 Å), ATP-analog/sangivamycin co-crystals, structural comparison with AGC family members The Journal of biological chemistry High 26032409
2017 GRK5 forms a dynamic complex with agonist-occupied β2AR involving large conformational changes at the RH/catalytic domain interface; contacts occur between β2AR intracellular loops 2 and 3 and C-terminus with GRK5 RH bundle subdomain, membrane-binding surface, and kinase catalytic cleft, respectively. Cross-linking mass spectrometry, hydrogen-deuterium exchange MS, electron microscopy, mutagenesis, molecular dynamics simulations, computational docking Cell High 28431242
2014 The RGS domain of GRK5 contains a hydrophobic dimeric interface (HDI) region that mediates GRK5 self-association/dimerization and is critical for plasma membrane localization; disruption of dimerization (M165E/F166E) reduces PM localization and impairs PAR1-induced calcium release regulation, which is rescued by forced dimerization or by adding an extra membrane-binding region. GRK5/GRK4 chimeras, point mutagenesis, co-immunoprecipitation, acceptor photobleaching FRET, calcium release functional assay Molecular biology of the cell Medium 24807909
2019 Ca2+·CaM binds primarily to the small lobe of the GRK5 kinase domain near elements critical for receptor interaction and membrane association, inhibiting receptor phosphorylation while activating the kinase for phosphorylation of soluble substrates; using the natural product malbrancheamide as a probe, the C-terminal lobe of CaM was shown to regulate membrane binding while the N-terminal lobe regulates receptor phosphorylation and kinase activation; in cells, malbrancheamide attenuates GRK5 nuclear translocation and blocks the hypertrophic response. Small-angle X-ray scattering, negative-stain EM, natural product chemical probe (malbrancheamide), in-cell nuclear translocation assay, hypertrophic gene expression Proceedings of the National Academy of Sciences of the United States of America High 31337679
2020 Crystal/cryo structure of GRK5–calmodulin complex reveals that CaM N and C domains bind independently to two helical regions at GRK5 N and C termini: the C domain disrupts membrane association facilitating cytoplasmic translocation, while the N domain activates GRK5 via ordering of the amphipathic αN-helix and allosteric disruption of kinase-RH domain interaction, enabling phosphorylation of cytoplasmic substrates. Cryo-EM/crystal structure, molecular dynamics simulations, biochemical kinase assays, localization experiments Molecular cell High 33321095
2020 GRK5 phosphorylates and inhibits the cardiac mineralocorticoid receptor (MR) upon β2-adrenergic receptor activation in cardiomyocytes, suppressing aldosterone-induced MR transcriptional activity; GRK5 deletion augments MR transcriptional activity and GRK5 is necessary for protective effects of eplerenone against aldosterone-induced apoptosis. CRISPR/Cas9 GRK5 deletion in H9c2 cells, GRK5 overexpression, co-immunoprecipitation, MR luciferase reporter, adult rat ventricular myocytes International journal of molecular sciences Medium 32326036
2020 GRK5 is necessary to promote agonist-induced dissociation of SAP97 from β1AR; cardiac-specific deletion of GRK5 prevents adrenergic-induced dissociation of the β1AR-SAP97 complex and prevents increases in CaMKII activity in hearts. Cardiac-specific GRK5 conditional KO mice, co-immunoprecipitation of β1AR-SAP97 complex, CaMKII activity measurement after isoproterenol challenge Circulation research Medium 32507058
2021 Nuclear translocation of GRK5 is involved in cardiac fibroblast activation; fibroblast-specific GRK5 deletion inhibits angiotensin II-mediated fibroblast activation in vitro and reduces cardiac fibrosis and hypertrophy after chronic AngII infusion or ischemic injury in vivo. Adult cardiac fibroblast GRK5 KO, fibroblast-specific conditional KO mice, AngII infusion model, MI model, nuclear translocation assay Proceedings of the National Academy of Sciences of the United States of America High 33500351
2021 A peptide encoding the GRK5 N-terminal (GRK5nt) CaM-binding domain acts as a competitive inhibitor by binding Ca2+-CaM and preventing its association with endogenous GRK5, thereby blocking GRK5 nuclear accumulation after pressure overload and attenuating pathological NFAT and NF-κB transcription and cardiac hypertrophy. Adenoviral GRK5nt expression in NRVMs, transgenic cardiomyocyte-specific TgGRK5nt mice, TAC model, CaM-binding co-immunoprecipitation, NFAT/NF-κB reporters Science signaling High 33785612
2022 Heterotrimeric Gq acts as a determinant of GRK subtype selectivity: upon Ang II stimulation of AT1R, β-arrestin recruitment depends on both GRK2/3 and GRK5/6; with β-arrestin-biased ligand TRV027 or pharmacological/genetic loss of Gq, GRK selectivity shifts to solely GRK5/6. Single-molecule imaging shows that under Gq-inactive conditions, AT1R and GRK5 (but not GRK2) relocate to an immobile phase. GRK-selective pharmacological inhibition, GRK genetic knockout, β-arrestin recruitment assay (BRET/NanoBiT), single-molecule live-cell imaging Nature communications High 35078997
2022 Catalytic inactivation of GRK5 (K215R knock-in mice) causes marked decline in cardiac function with increased apoptosis and fibrosis at baseline; nuclear restriction of K215R GRK5 in cardiomyocytes enhances cell death with higher p53 levels; K215R mutation promotes fibroblast-to-myofibroblast transition. Knock-in mouse model (K215R catalytic-dead GRK5), echocardiography, histology, in vitro cardiomyocyte and fibroblast studies JACC. Basic to translational science Medium 35540100
2022 GRK5 is essential for finerenone-induced GRK5-dependent MR phosphorylation and inverse agonism in cardiomyocytes; GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity, establishing GRK5 as a co-repressor of the cardiac mineralocorticoid receptor. GRK5 genetic deletion (H9c2 cells), MR luciferase reporter assay, MR phosphorylation assay, finerenone vs. eplerenone comparison World journal of cardiology Medium 35582468
2018 GRK5 regulates phosphorylation of HDAC5 in pancreatic β cells; β cell-specific Grk5 KO mice show impaired glucose tolerance with reduced β cell mass and upregulation of cell cycle inhibitor Cdkn1a, with reduced transcription of immediate-early genes (Nr4a1, Fosb, Junb, Arc, Egr1, Srf) downstream of HDAC5 phosphorylation. β cell-specific Grk5 KO mice, glucose tolerance test, β cell mass quantification, RNA sequencing, HDAC5 phosphorylation assay iScience Medium 37520700
2024 GRK5 phosphorylates HDAC6 in chondrocytes, promoting HDAC6 phosphorylation; KLF9 transcriptionally drives GRK5 expression by directly targeting the GRK5 promoter; GRK5 knockdown eliminates KLF9 overexpression effects on chondrocyte ECM degradation and apoptosis in osteoarthritis. ChIP/luciferase for KLF9-GRK5 promoter binding, GRK5-HDAC6 co-immunoprecipitation, HDAC6 phosphorylation assay, siRNA knockdown, HDAC6 inhibitor rescue Communications biology Medium 39779910
2024 GRK5 phosphorylates HDAC5 and regulates the HDAC5/Smad3 pathway in renal fibrosis; nuclear-translocated GRK5 upregulates HDAC5, which prevents MEF2A transcriptional activity and represses Smad7, leading to Smad3 activation. GRK5 inhibition attenuates renal fibrosis. GRK5 overexpression/knockdown in renal cells, nuclear fractionation, HDAC5 and Smad3 pathway Western blot, MEF2A reporter assay FASEB journal Medium 38206179
2025 GRK5 inhibition rescues p.Phe508del-CFTR plasma membrane traffic and function in human airway cells; GRK5 siRNA knockdown validated in a genome-wide siRNA screen of >9,000 genes as a regulator of p.Phe508del-CFTR plasma membrane rescue. Genome-wide siRNA high-content microscopy screen, siRNA validation, functional CFTR assay in primary and immortalized airway cells iScience Medium 40040803
2024 GRK5 is required for FPR2 endocytosis: GRK5 phosphorylates FPR2 C-terminal sites enabling β-arrestin recruitment; however, β-arrestin recruitment per se is not essential for FPR2 endocytosis—rather, β-arrestin determines postendocytic delivery to subcellular compartments and the magnitude of downstream ERK signaling. GRK5-selective pharmacological/genetic manipulation, β-arrestin KO cells, β-arrestin recruitment BRET assay, internalization assay, subcellular trafficking imaging The Journal of biological chemistry Medium 39706266
2018 PHLPP2 physically interacts with endogenous GRK5 in neonatal rat ventricular myocytes; PHLPP2 knockdown enhances PE-induced nuclear accumulation of GRK5 and potentiates hypertrophic growth, while PHLPP2 overexpression (requiring phosphatase activity) blocks PE-induced GRK5 nuclear accumulation and hypertrophy in a GRK5-dependent manner. Co-immunoprecipitation, siRNA knockdown of PHLPP2, adenoviral overexpression, nuclear fractionation, cell size measurement, fetal gene expression The Journal of biological chemistry Medium 29628444
2026 GRK5 regulates PAR1 desensitization in platelets: GG homozygotes for rs10886430 have ~90% lower GRK5 protein in platelets, leading to reduced PAR1 internalization, elevated platelet responsiveness to thrombin and PAR1 agonist (but not PAR4 agonist), and enhanced thrombus formation in vitro and in vivo. These findings were corroborated in GRK5-/- iPSC-derived megakaryocytes, Grk5-deficient murine platelets, and with GRK5 inhibitor treatment. Human platelet GRK5 protein quantification in GG vs AA donors, PAR1 internalization assay, platelet activation functional assay, microfluidic endothelialized system, GRK5 KO iPSC-megakaryocytes, Grk5-deficient mouse platelets, murine arterial thrombosis model Blood High 41557909
2007 GRK5 forms a protein complex with the GABA(B2) subunit of GABA(B) receptors at the plasma membrane (demonstrated by FRET between GRK5 and GB2R-Venus, confirmed by co-immunoprecipitation), mediating desensitization of GABA(B) receptor-operated K+ currents upon repeated baclofen application. FRET (cerulean/Venus fluorophores), co-immunoprecipitation, Xenopus oocyte electrophysiology, BHK cell coexpression Journal of cellular physiology Medium 17013811
2014 CB1 receptor signaling in smooth muscle proceeds via GRK5 phosphorylation (not Gβγ): kinase-deficient GRK5(K215R) abolishes CB1 receptor internalization and ERK1/2/Src kinase activation; β-arrestin1/2 siRNA abolishes ERK1/2 activity; GRK5/β-arrestin-activated ERK1/2 phosphorylates RGS4 at Ser103/Ser108 to accelerate Gαq inactivation and inhibit muscle contraction. Kinase-deficient GRK5 K215R expression, β-arrestin siRNA, CB1 receptor internalization assay, ERK1/2 activity assay, RGS4 phosphorylation assay, RGS4 mutant (S103A/S108A), contraction assay American journal of physiology. Gastrointestinal and liver physiology High 24407588

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nature medicine 264 18425130
1994 Identification, purification, and characterization of GRK5, a member of the family of G protein-coupled receptor kinases. The Journal of biological chemistry 161 8120045
1993 Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. Proceedings of the National Academy of Sciences of the United States of America 144 7685906
2017 Structural and Functional Analysis of a β2-Adrenergic Receptor Complex with GRK5. Cell 139 28431242
1997 Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C. The Journal of biological chemistry 110 9013639
1994 Expression, purification, and characterization of the G protein-coupled receptor kinase GRK5. The Journal of biological chemistry 95 8288567
1994 Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5. The Journal of biological chemistry 87 8144599
2022 Heterotrimeric Gq proteins act as a switch for GRK5/6 selectivity underlying β-arrestin transducer bias. Nature communications 86 35078997
2001 Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine(2A) receptor desensitization and resensitization reveal an arrestin-, GRK2-, and GRK5-independent mode of regulation in human embryonic kidney 293 cells. Molecular pharmacology 77 11641430
2004 A predicted amphipathic helix mediates plasma membrane localization of GRK5. The Journal of biological chemistry 75 14976207
2014 GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity. Circulation research 70 25332207
2002 Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats. Hypertension (Dallas, Tex. : 1979) 70 12052842
2006 GRK5 deficiency leads to early Alzheimer-like pathology and working memory impairment. Neurobiology of aging 65 17011668
2009 Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling. The EMBO journal 60 19661922
2011 Polymorphisms in genes coding for GRK2 and GRK5 and response differences in antihypertensive-treated patients. Pharmacogenetics and genomics 50 21127457
2021 GRK5 is a regulator of fibroblast activation and cardiac fibrosis. Proceedings of the National Academy of Sciences of the United States of America 49 33500351
2014 G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer. Cancer research 49 24755472
1998 Regulation of G protein-coupled receptor kinase 5 (GRK5) by actin. The Journal of biological chemistry 45 9685424
2016 "Canonical and non-canonical actions of GRK5 in the heart". Journal of molecular and cellular cardiology 44 26829117
2013 Regulation of nuclear factor κB (NF-κB) in the nucleus of cardiomyocytes by G protein-coupled receptor kinase 5 (GRK5). The Journal of biological chemistry 44 24174526
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
2015 G Protein-Coupled Receptor Kinase 2 (GRK2) and 5 (GRK5) Exhibit Selective Phosphorylation of the Neurotensin Receptor in Vitro. Biochemistry 42 26120872
2022 G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure. Cardiovascular research 41 33560342
2018 GRK5 functions as an oncogenic factor in non-small-cell lung cancer. Cell death & disease 38 29463786
2015 Atomic Structure of GRK5 Reveals Distinct Structural Features Novel for G Protein-coupled Receptor Kinases. The Journal of biological chemistry 36 26032409
2009 GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization. The Journal of biological chemistry 35 19478075
2012 Involvement of nuclear factor κB (NF-κB) signaling pathway in regulation of cardiac G protein-coupled receptor kinase 5 (GRK5) expression. The Journal of biological chemistry 33 22389501
2020 GRK5 Inhibition Attenuates Cartilage Degradation via Decreased NF-κB Signaling. Arthritis & rheumatology (Hoboken, N.J.) 32 31696655
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
2020 Structure of a GRK5-Calmodulin Complex Reveals Molecular Mechanism of GRK Activation and Substrate Targeting. Molecular cell 31 33321095
2013 Distinct structural features of G protein-coupled receptor kinase 5 (GRK5) regulate its nuclear localization and DNA-binding ability. PloS one 31 23658733
2010 GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity. The Journal of biological chemistry 30 21041302
2021 Circ_0001821 knockdown suppresses growth, metastasis, and TAX resistance of non-small-cell lung cancer cells by regulating the miR-526b-5p/GRK5 axis. Pharmacology research & perspectives 29 34219377
2020 Antagonistic Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Reveal GRK5-Mediated Cardioprotection via Mineralocorticoid Receptor Inhibition. International journal of molecular sciences 29 32326036
2012 Parallel changes in neuronal AT1R and GRK5 expression following exercise training in heart failure. Hypertension (Dallas, Tex. : 1979) 29 22753221
2018 GRK5 - A Functional Bridge Between Cardiovascular and Neurodegenerative Disorders. Frontiers in pharmacology 28 30618771
2012 GRK5 ablation contributes to insulin resistance. Biochemical and biophysical research communications 28 23111327
2011 GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis. The Journal of cell biology 27 21930777
2007 Phosphorylation of the beta2-adrenergic receptor in plasma membranes by intrinsic GRK5. Biochemistry 27 18034461
2013 G-protein coupled receptor kinase (GRK)-5 regulates proliferation of glioblastoma-derived stem cells. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 25 23693024
2020 GRK5 Controls SAP97-Dependent Cardiotoxic β1 Adrenergic Receptor-CaMKII Signaling in Heart Failure. Circulation research 23 32507058
2019 Perturbation of the interactions of calmodulin with GRK5 using a natural product chemical probe. Proceedings of the National Academy of Sciences of the United States of America 23 31337679
2019 GRK2 and GRK5 as therapeutic targets and their role in maladaptive and pathological cardiac hypertrophy. Expert opinion on therapeutic targets 22 30701991
2014 Overlapping and opposing functions of G protein-coupled receptor kinase 2 (GRK2) and GRK5 during heart development. The Journal of biological chemistry 22 25104355
2008 GRK5 deficiency exaggerates inflammatory changes in TgAPPsw mice. Journal of neuroinflammation 22 18522748
2021 Targeting GRK5 for Treating Chronic Degenerative Diseases. International journal of molecular sciences 21 33671974
2014 GRK5 dysfunction accelerates tau hyperphosphorylation in APP (swe) mice through impaired cholinergic activity. Neuroreport 20 24598771
2009 GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans. Pharmacogenomics 20 19842931
2014 Inhibitory signaling by CB1 receptors in smooth muscle mediated by GRK5/β-arrestin activation of ERK1/2 and Src kinase. American journal of physiology. Gastrointestinal and liver physiology 19 24407588
2005 Chronic beta-adrenergic receptor stimulation enhances the expression of G-Protein coupled receptor kinases, GRK2 and GRK5, in both the heart and peripheral lymphocytes. Circulation journal : official journal of the Japanese Circulation Society 19 16041172
2019 Downregulation of GRK5 hampers the migration of breast cancer cells. Scientific reports 18 31664083
2018 GRK5 influences the phosphorylation of tau via GSK3β and contributes to Alzheimer's disease. Journal of cellular physiology 18 30511419
2018 GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence. The international journal of neuropsychopharmacology 17 30060048
2016 Dual role of GRK5 in cancer development and progression. Translational medicine @ UniSa 17 27326393
2014 The regulator of G protein signaling (RGS) domain of G protein-coupled receptor kinase 5 (GRK5) regulates plasma membrane localization and function. Molecular biology of the cell 17 24807909
2008 Augmented axonal defects and synaptic degenerative changes in female GRK5 deficient mice. Brain research bulletin 16 18955119
1999 Enhanced GRK5 expression in the hearts of cardiomyopathic hamsters, J2N-k. Biochemical and biophysical research communications 16 10448093
2018 The Amino-Terminal Domain of GRK5 Inhibits Cardiac Hypertrophy through the Regulation of Calcium-Calmodulin Dependent Transcription Factors. International journal of molecular sciences 15 29543709
2018 PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) regulates G-protein-coupled receptor kinase 5 (GRK5)-induced cardiac hypertrophy in vitro. The Journal of biological chemistry 15 29628444
2014 GRK5 intronic (CA)n polymorphisms associated with type 2 diabetes in Chinese Hainan Island. PloS one 15 24594703
2012 GRK5 deficiency decreases diet-induced obesity and adipogenesis. Biochemical and biophysical research communications 15 22507984
2020 KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure. Biomolecules & therapeutics 14 32856617
2015 Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 14 26066465
1995 Chromosomal mapping of the genes GPRK5 and GPRK6 encoding G protein-coupled receptor kinases GRK5 and GRK6. Cytogenetics and cell genetics 14 7789183
2018 GRK5 Regulates Social Behavior Via Suppression of mTORC1 Signaling in Medial Prefrontal Cortex. Cerebral cortex (New York, N.Y. : 1991) 13 28334166
2022 Targeting GRK2 and GRK5 for treating chronic degenerative diseases: Advances and future perspectives. European journal of medicinal chemistry 12 36055000
2017 The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk. Oncotarget 12 29069820
2015 Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure. Journal of translational medicine 12 25638254
2022 Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels. JACC. Basic to translational science 11 35540100
2023 TRPA1 deficiency attenuates cardiac fibrosis via regulating GRK5/NFAT signaling in diabetic rats. Biochemical pharmacology 10 37380112
2021 A peptide of the N terminus of GRK5 attenuates pressure-overload hypertrophy and heart failure. Science signaling 10 33785612
2018 A variant of GRK5 is associated with the therapeutic efficacy of repaglinide in Chinese Han patients with type 2 diabetes mellitus. Drug development research 10 29663513
2015 β2- and β1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases. Journal of cardiovascular pharmacology 10 26248277
2003 Endosome sorting of beta 2-adrenoceptors is GRK5 independent. British journal of pharmacology 10 14691047
2025 KLF9-GRK5-HDAC6 axis aggravates osteoarthritis pathogenesis by promoting chondrocyte extracellular matrix degradation and apoptosis. Communications biology 9 39779910
2016 GRK5 deficiency leads to susceptibility to intermittent hypoxia-induced cognitive impairment. Behavioural brain research 9 26778781
2016 GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability. Scientific reports 9 27193825
2024 GRK5 promoted renal fibrosis via HDAC5/Smad3 signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 38206179
2021 Cannabinoid 2 receptors regulate dopamine 2 receptor expression by a beta-arrestin 2 and GRK5-dependent mechanism in neuronal cells. Neuroscience letters 8 33838258
2011 Overlapping and distinct roles of GRK5 in TLR2-, and TLR3-induced inflammatory response in vivo. Cellular immunology 8 22078319
2008 Protective effect of a GRK5 polymorphism on heart failure and its interaction with beta-adrenergic receptor antagonists. Pharmacogenomics 8 18855542
2021 Association between gene polymorphism of GRK5 and breast cancer risk in Chinese population. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 7 34268929
2019 GRK5 promotes tumor progression in renal cell carcinoma. Neoplasma 7 30784280
2015 Involvement of NFκB signaling in mediating the effects of GRK5 on neural stem cells. Brain research 7 25732260
2024 Porphyromonas gingivalis virulence factors induce toxic effects in SH-SY5Y neuroblastoma cells: GRK5 modulation as a protective strategy. Journal of biotechnology 6 39033880
2023 Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic β-cell proliferation via phosphorylation of HDAC5. iScience 6 37520700
2020 Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal. Oncotarget 6 32363002
2015 GRK5 Polymorphisms and Postoperative Atrial Fibrillation following Coronary Artery Bypass Graft Surgery. Scientific reports 6 26235218
2024 GRK5 regulates endocytosis of FPR2 independent of β-arrestins. The Journal of biological chemistry 5 39706266
2022 GRK5 Deficiency Causes Mild Cognitive Impairment due to Alzheimer's Disease. Journal of Alzheimer's disease : JAD 5 34958040
2016 GRK5-Knockout Mice Generated by TALEN-Mediated Gene Targeting. Animal biotechnology 5 27565865
2026 Understanding how a highly prevalent GRK5 polymorphism affects platelets and enhances thrombotic risk. Blood 4 41557909
2023 GRK5-mediated inflammation and fibrosis exert cardioprotective effects during the acute phase of myocardial infarction. FEBS open bio 4 36633120
2022 GRK5 is an essential co-repressor of the cardiac mineralocorticoid receptor and is selectively induced by finerenone. World journal of cardiology 4 35582468
2022 Genetic Arg-304-His substitution in GRK5 protects against sepsis progression by alleviating NF-κB-mediated inflammation. International immunopharmacology 4 36584571
2018 Single Nucleotide Polymorphisms in the G-Protein Coupled Receptor Kinase 5 (GRK5) Gene are associated with Plasma LDL-Cholesterol Levels in Humans. Scientific reports 4 29773828
2016 The analysis of heterotaxy patients reveals new loss-of-function variants of GRK5. Scientific reports 4 27618959
2025 GRK5 is required for adipocyte differentiation through ERK activation. International journal of obesity (2005) 3 39838122
2025 Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators. iScience 3 40040803
2022 GRK5 Deficiency in the Hippocampus Leads to Cognitive Impairment via Abnormal Microglial Alterations. Molecular neurobiology 2 36525154

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