Affinage

GRK3

G protein-coupled receptor kinase 3 · UniProt P35626

Length
688 aa
Mass
79.7 kDa
Annotated
2026-06-10
40 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRK3 is a serine/threonine kinase that mediates agonist-dependent (homologous) desensitization of G protein-coupled receptors by phosphorylating activated receptors and recruiting beta-arrestins, a function it serves across diverse receptor systems including olfactory odorant receptors (PMID:9325250), CRF1 (PMID:11247813), opioid receptors (PMID:16648139, PMID:16982618, PMID:33060647), CXCR4 (PMID:18274673), P2X7 (PMID:15728711), ACKR4 (PMID:32391018), and broadly across platelet GPCRs (PMID:39419098). At the opioid receptors, GRK3-catalyzed receptor phosphorylation (e.g. KOR Ser369) is the obligatory upstream step that drives arrestin3 recruitment and downstream activation of p38 MAPK and ERK1/2, in an agonist-efficacy-dependent manner whereby high-efficacy agonists such as fentanyl engage the pathway more strongly than morphine (PMID:16648139, PMID:16982618, PMID:14662727). Loss of GRK3 removes this attenuating brake: knockout platelets show potentiated aggregation, granule secretion, and AKT/ERK signaling to GPCR but not non-GPCR agonists (PMID:39419098), and GRK3 silencing recapitulates the impaired CXCR4 internalization seen in WHIM syndrome (PMID:18274673). The receptor-targeting specificity of GRK3 in vivo is determined by its multidomain architecture: its C-terminal pleckstrin-homology region binds free Gbetagamma dimers (not intact heterotrimers) to drive membrane recruitment (PMID:19258039, PMID:39579957), its N-terminal domain binds RKIP and engages the beta2-adrenoceptor (PMID:31604529), and an isolated C-terminal fragment acts as a competitive inhibitor revealing alpha1-adrenergic receptor selectivity in the heart (PMID:18165681, PMID:9746479). Distinct from its kinase function, the RGS-homology domain of GRK3 binds Gq and suppresses L-DOPA-induced dyskinesia independently of catalytic activity (PMID:26043205). GRK3 also phosphorylates the non-GPCR substrate HDAC2 at Ser394 to enhance epigenetic repression and promote neuroendocrine differentiation and angiogenesis in prostate cancer (PMID:37543278, PMID:27191986).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Established that GRK3 is physiologically required for rapid agonist-induced GPCR desensitization, using odorant receptor signaling as the first in vivo demonstration of its desensitization role.

    Evidence Targeted GRK3 knockout mice with cilia preparation cAMP and electrophysiological assays

    PMID:9325250

    Open questions at the time
    • Direct phosphorylation of odorant receptors not biochemically demonstrated
    • Arrestin involvement not addressed in this system
  2. 1998 Medium

    Showed GRK3 has distinct in vivo substrate selectivity, attenuating thrombin-mediated MAP kinase signaling in heart while sparing beta-adrenergic and angiotensin II receptors, distinguishing it from GRK2 and GRK5.

    Evidence Cardiac-specific transgenic GRK3 overexpression with hemodynamic and MAP kinase assays

    PMID:9746479

    Open questions at the time
    • Molecular basis of substrate selectivity not defined
    • Overexpression may not reflect endogenous specificity
  3. 2001 Medium

    Identified GRK3 as the primary kinase for CRF1 receptor homologous desensitization, distinguishing it from GRK2 and from PKA-mediated heterologous desensitization.

    Evidence Antisense knockdown (ODN and cDNA) with PKA inhibitors and cAMP accumulation in Y-79 cells

    PMID:11247813

    Open questions at the time
    • Direct CRF1 phosphorylation not shown
    • Single cell type
  4. 2003 High

    Demonstrated agonist-efficacy-dependent involvement of GRK3 in opioid tolerance, linking receptor phosphorylation by GRK3 to high-efficacy opioid (fentanyl) but not low-efficacy (morphine) responses.

    Evidence GRK3 knockout mice with antinociception behavior and hippocampal slice electrophysiology

    PMID:14662727

    Open questions at the time
    • Specific phosphorylated residues not mapped here
    • Arrestin step not yet established
  5. 2003 Medium

    Revealed cross-receptor regulation in which beta2-AR-driven upregulation of GRK3 enables chronic alpha2A-adrenoceptor desensitization, placing GRK3 expression itself under receptor control.

    Evidence Pharmacological antagonism, GRK2/3 antisense DNA, and radioligand binding in neuroblastoma cells

    PMID:12642394

    Open questions at the time
    • GRK2 vs GRK3 contributions not fully separated
    • Transcriptional mechanism not defined here
  6. 2005 Medium

    Linked GRK3 to receptor internalization machinery, showing agonist-induced GRK3 binding to P2X7 alongside beta-arrestin-2 and dynamin to drive clathrin-mediated internalization.

    Evidence Co-immunoprecipitation and beta-arrestin-2 redistribution imaging in P2X7-expressing cells

    PMID:15728711

    Open questions at the time
    • No direct phosphorylation assay or mutagenesis
    • Binding correlation rather than catalytic requirement
  7. 2006 High

    Defined the mechanistic chain at opioid receptors: GRK3 phosphorylates KOR at Ser369 to recruit arrestin3 and activate p38, and phosphorylates MOR to enable arrestin3-dependent ERK1/2, with efficacy-dependence resolved by dominant-positive arrestin rescue.

    Evidence GRK3 knockout neurons/astrocytes, KOR-S369A mutant, dominant-positive arrestin3-(R170E) rescue, siRNA in primary striatal cells

    PMID:16648139 PMID:16982618

    Open questions at the time
    • MOR phosphorylation site not mapped
    • In vivo relevance to behavior not directly tested in these studies
  8. 2006 Low

    Observed that mood stabilizers increase membrane translocation of GRK3, providing a candidate link to psychiatric pharmacology.

    Evidence Immunoblotting of membrane/cytosol fractions from lithium/carbamazepine-treated rat cortex

    PMID:16697355

    Open questions at the time
    • Single method, no functional consequence measured
    • Mechanism of translocation unknown
  9. 2007 Medium

    Identified the transcriptional control of GRK3 by CRF1-ERK1/2 signaling via Sp-1 and Ap-2, and a GRK3-GRK2 cross-regulatory loop through inositol phosphates.

    Evidence Pharmacological ERK inhibition and transcription factor assays in CATH.a cells; antisense GRK3 with InsP/GRK2 measurement in U937 cells

    PMID:17433264 PMID:17583697

    Open questions at the time
    • GRK2 cross-regulation is Low confidence and indirect
    • Direct promoter occupancy not shown
  10. 2008 High

    Connected GRK3 to human disease by showing its loss causes WHIM-syndrome-like defective CXCR4 desensitization, with overexpression restoring normal CXCR4 attenuation in patient cells.

    Evidence Bidirectional siRNA/overexpression in patient leukocytes and fibroblasts with internalization and chemotaxis assays

    PMID:18274673

    Open questions at the time
    • Direct CXCR4 phosphorylation by GRK3 not shown
    • Genetic cause of GRK3 dysregulation in patients not defined
  11. 2007 High

    Resolved cardiac receptor selectivity, showing GRK3 specifically desensitizes alpha1-adrenergic receptors and that a competitive C-terminal fragment de-represses alpha1-AR signaling and alters cardiovascular physiology.

    Evidence Cardiac transgenic GRK3ct inhibitor with ERK assays, blood pressure telemetry, and working heart preparations

    PMID:18165681

    Open questions at the time
    • Mechanistic basis of alpha1-AR preference not structurally defined
  12. 2009 High

    Characterized the GRK3 C-terminal domain as a selective sensor of free Gbetagamma versus heterotrimer, explaining how GRK3 is recruited to membranes upon G protein activation and enabling kinetic measurement of heterotrimer dissociation.

    Evidence FRET/BRET with GRK3ct fusion sensors and venus-Gbetagamma in live cells

    PMID:19258039

    Open questions at the time
    • Does not address kinase activation downstream of recruitment
    • Gbeta subtype selectivity not yet examined
  13. 2015 High

    Separated a kinase-independent function of GRK3, showing its RGS-homology domain binds Gq and suppresses L-DOPA-induced dyskinesia without catalytic activity.

    Evidence Striatal viral expression of GRK3 domain variants and microRNA knockdown in hemiparkinsonian rats with behavior, deltaFosB IHC, and Gq co-IP

    PMID:26043205

    Open questions at the time
    • Structural detail of RH-Gq interaction not resolved
    • Endogenous contribution versus overexpression not separated
  14. 2016 Medium

    Placed GRK3 downstream of CREB as a direct transcriptional target driving kinase-dependent neuroendocrine differentiation in prostate cancer.

    Evidence CREB target validation, GRK3 overexpression/siRNA, kinase-dead mutant, NE marker assays in prostate cancer models

    PMID:27191986

    Open questions at the time
    • Relevant kinase substrate not identified in this study
    • Single lab
  15. 2019 Medium

    Defined the GRK3 N-terminal domain as a docking module that binds RKIP and contacts the beta2-adrenoceptor, with a steric-interference fragment blocking receptor phosphorylation and internalization.

    Evidence Reciprocal co-IP/pull-down and beta2-AR phosphorylation/internalization plus cardiomyocyte contractility assays

    PMID:31604529

    Open questions at the time
    • RKIP regulatory role on GRK3 kinase activity not quantified
    • Single lab
  16. 2020 High

    Quantified the relative and partly redundant roles of GRK2 and GRK3 in MOR beta-arrestin recruitment and internalization, and showed GRK3 is recruited to ACKR4 ahead of beta-arrestins to facilitate their recruitment.

    Evidence CRISPR GRK2/3 single and double knockouts with rescue and BRET/FACS assays; BRET recruitment kinetics and beta-arrestin KO cells for ACKR4

    PMID:32391018 PMID:33060647

    Open questions at the time
    • Determinants of GRK2 vs GRK3 preference at each receptor unresolved
    • ACKR4 study is Medium confidence with partial inhibition effects
  17. 2021 Medium

    Linked GRK3 loss to immunomodulatory and dopaminergic dysregulation, with elevated brain IL-1beta, kynurenic acid turnover, dopamine neuron hyperactivity, and disrupted prepulse inhibition.

    Evidence Grk3-/- mice with behavioral, electrophysiological, and biochemical assays

    PMID:33976392

    Open questions at the time
    • Causal GRK3 substrate in these phenotypes not identified
    • Receptor-level mechanism not pinpointed
  18. 2023 Medium

    Established a non-GPCR substrate for GRK3, showing it phosphorylates HDAC2 at Ser394 to enhance epigenetic repression of TSP1 and REST, promoting neuroendocrine differentiation and angiogenesis under androgen deprivation and hypoxia.

    Evidence Co-IP, S394 phosphosite identification, GRK3/HDAC2 KD/OE, and REST/TSP1 reporter and ChIP assays with in vivo validation

    PMID:37543278

    Open questions at the time
    • Direct in vitro kinase assay on HDAC2 not detailed
    • Single lab
  19. 2024 High

    Refined membrane recruitment specificity, showing Gbeta5 selectively activates GRK3 (not GRK2) at MOR through confined membrane domains in a freely diffusible state, engaged by the biased agonist oliceridine, while broadening GRK3's role to general platelet GPCR desensitization.

    Evidence Genome-edited GRK/Gbeta knockout lines with BRET and single-molecule imaging for MOR; GRK3 knockout platelets with aggregation, secretion, phospho-AKT/ERK, and bleeding time assays

    PMID:39419098 PMID:39579957

    Open questions at the time
    • Structural basis of Gbeta5 selectivity unresolved
    • Physiological consequences of the Galphaz-Gbeta5-GRK3 axis in vivo not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GRK3 achieves its receptor-by-receptor substrate selectivity at the molecular level and what governs the choice between its kinase-dependent and RGS/RH-domain-dependent functions in a given tissue.
  • No structural model linking domain architecture to specific receptor recognition
  • Tissue-specific determinants of kinase versus scaffolding function unknown
  • Endogenous non-GPCR substrate repertoire largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-109582 Hemostasis 1 R-HSA-4839726 Chromatin organization 1
Partners
ADRB2ARRB2ARRB3GNAQGNB1GNB5HDAC2RKIP

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 GRK3 is required for agonist-induced desensitization of odorant receptors in the olfactory epithelium; cilia preparations from GRK3-knockout mice lack fast agonist-induced desensitization and show markedly reduced cAMP generation following odorant stimulation. Targeted gene disruption (GRK3 knockout mice), cilia preparation functional assays measuring cAMP and electrophysiological desensitization The Journal of biological chemistry High 9325250
2001 GRK3 mediates homologous desensitization of CRF1 receptors; antisense knockdown of GRK3 (but not GRK2) in Y-79 cells reduced GRK3 mRNA/protein and inhibited CRF1 receptor desensitization by ~55–65%; PKA inhibition did not attenuate desensitization, placing GRK3 as the primary kinase mediating CRF1 homologous desensitization. Antisense oligonucleotide knockdown, antisense cDNA transfection, PKA inhibitors, cAMP accumulation assay American journal of physiology. Regulatory, integrative and comparative physiology Medium 11247813
2003 GRK3-mediated receptor phosphorylation is required for opioid analgesic tolerance; GRK3-knockout mice show significantly reduced tolerance to fentanyl (high-efficacy opioid) both behaviorally (antinociception) and electrophysiologically (hippocampal slices), while morphine tolerance is less affected, demonstrating agonist-efficacy-dependent GRK3 involvement. GRK3 knockout mice, hot-plate antinociception assay, hippocampal slice electrophysiology British journal of pharmacology High 14662727
2003 Chronic adrenaline-induced desensitization of alpha2A-adrenoceptors requires beta2-adrenoceptor-dependent upregulation of GRK3; propranolol (beta-AR antagonist) blocked GRK3 upregulation and alpha2A-AR desensitization/downregulation caused by chronic adrenaline, while GRK2/3 antisense DNA also blocked this effect. Pharmacological antagonism (propranolol), GRK2/3 antisense DNA, radioligand binding, functional assays in BE(2)-C neuroblastoma cells British journal of pharmacology Medium 12642394
2005 ATP stimulation of P2X7 receptor increases binding of GRK3 to the 85-kDa P2X7 receptor form, along with beta-arrestin-2 and dynamin, promoting beta-arrestin-2-dependent receptor internalization into clathrin domains. Western blot, co-immunoprecipitation/binding assay, beta-arrestin-2 redistribution imaging in CaSki and HEK-293-hP2X7-R cells American journal of physiology. Cell physiology Medium 15728711
2006 KOR activation of p38 MAPK requires GRK3-mediated phosphorylation of serine-369 on KOR and subsequent arrestin3 recruitment; p38 activation was absent in GRK3-knockout neurons and astrocytes, and a dominant-positive arrestin3-(R170E) rescued p38 activation even in KOR-S369A mutant cells. GRK3 knockout mice, KOR point mutation (S369A), dominant-positive arrestin3-(R170E) transfection, siRNA knockdown of arrestin3, phospho-p38 immunolabeling in primary striatal neurons and astrocytes The Journal of biological chemistry High 16648139
2006 MOR activation of ERK1/2 in striatal neurons requires GRK3-mediated receptor phosphorylation and arrestin3 association; fentanyl-induced ERK1/2 activation was absent in GRK3-knockout neurons and was rescued by dominant-positive arrestin3-(R170E); morphine (low-efficacy) did not activate ERK1/2 unless dominant-positive arrestin3 was expressed. GRK3 knockout mice, dominant-positive arrestin3-(R170E) transfection, siRNA for arrestin3, MEK inhibitor U0126, phospho-ERK1/2 assays in primary striatal neurons The Journal of biological chemistry High 16982618
1998 Cardiac-specific overexpression of GRK3 in transgenic mice does not desensitize beta-adrenergic or angiotensin II receptors, but significantly attenuates thrombin-mediated p42/p44 MAP kinase activation, demonstrating distinct in vivo substrate specificity for GRK3 compared to GRK2 and GRK5. Cardiac-specific transgenic overexpression, in vivo hemodynamic assessment, MAP kinase activation assays The American journal of physiology Medium 9746479
2007 Cardiac GRK3 specifically desensitizes alpha1-adrenergic receptors; transgenic mice expressing the C-terminal GRK3 inhibitory fragment (GRK3ct) showed enhanced alpha1-AR-mediated ERK1/2 activation, elevated blood pressure, increased cardiac contractility (stroke volume, stroke work), and impaired diastolic relaxation at high preload. Cardiac-specific transgenic expression of GRK3ct competitive inhibitor, ERK1/2 activation assays in cardiomyocytes, radiotelemetric blood pressure, in vivo conductance micromanometry, ex vivo working heart preparations The Journal of biological chemistry High 18165681
2008 GRK3 specifically regulates CXCL12-promoted internalization and desensitization of CXCR4; GRK3 silencing in control cells recapitulated WHIM syndrome phenotypes (impaired CXCR4 internalization, enhanced chemotaxis), and GRK3 overexpression in WHIM patient leukocytes restored normal CXCR4 attenuation and chemotaxis. GRK3 siRNA knockdown, GRK3 overexpression in patient leukocytes and fibroblasts, CXCR4 internalization assays, chemotaxis assays The Journal of clinical investigation High 18274673
2009 The C-terminal domain of GRK3 (GRK3ct) fused to fluorescent proteins binds free Gbetagamma dimers but not intact rearranged heterotrimers, and FRET/BRET measurements using this sensor demonstrated that G protein heterotrimer dissociation occurs in living cells in under 100 ms. FRET and BRET using GRK3ct fusion proteins and venus-labeled Gbetagamma in live cells; freely diffusible probe, temporal resolution <100 ms Cellular signalling High 19258039
2006 Chronic lithium and carbamazepine (but not valproate) treatment increases GRK3 translocation from cytosol to membrane in rat frontal cortex, while GRK2 levels are unchanged, suggesting mood stabilizers act in part by increasing membrane GRK3. Immunoblotting of membrane and cytosol fractions from drug-treated rat frontal cortex Biological psychiatry Low 16697355
2007 GRK3 regulates GRK2 protein levels in U937 cells; antisense-mediated reduction of GRK3 increased inositol phosphate (InsP) levels, which in turn upregulated GRK2, establishing a cross-regulatory mechanism between GRK family members. Antisense knockdown of GRK3, immunoblotting for GRK2, InsP measurement in U937 cells Biochemical pharmacology Low 17433264
2007 CRF1 receptor activation upregulates GRK3 expression via an ERK1/2-mediated mechanism involving Sp-1 and Ap-2 transcription factors in CATH.a (locus coeruleus-derived) cells. Pharmacological ERK1/2 inhibition, transcription factor activation assays (Sp-1, Ap-2), GRK3 mRNA/protein measurement in CATH.a cells FEBS letters Medium 17583697
2015 GRK3 suppresses L-DOPA-induced dyskinesia (LID) through its RGS homology (RH) domain, not its kinase activity; kinase-dead GRK3 and isolated RH domain suppressed LID and ΔFosB accumulation, whereas GRK3 with disabled RH did not; RH domain binds striatal Gq. Viral vector-mediated striatal overexpression of GRK3 variants (WT, kinase-dead, RH domain, RH-dead mutant) and microRNA knockdown in hemiparkinsonian rats; behavioral scoring of abnormal involuntary movements; ΔFosB immunohistochemistry; Gq co-immunoprecipitation Scientific reports High 26043205
2016 GRK3 is a direct transcriptional target of CREB and promotes neuroendocrine differentiation (NED) of prostate cancer cells in a kinase activity-dependent manner; GRK3 overexpression increased NE marker expression, while GRK3 silencing blocked CREB-induced NED. ChIP/CREB target validation, GRK3 overexpression and siRNA knockdown, kinase-dead GRK3 mutant, NE marker expression assays in prostate cancer cell lines and mouse models Oncotarget Medium 27191986
2019 The N-terminal domain of GRK3 (residues 1–185) binds RKIP and directly interacts with beta2-adrenoceptors; overexpression of GRK3(1–185) prevented beta2-AR phosphorylation and internalization, increased receptor signaling in HEK293 cells, and enhanced cardiomyocyte contractility, demonstrating steric interference with GRK3-receptor interaction. Co-immunoprecipitation, pull-down assays, beta2-AR phosphorylation and internalization assays, HEK293 cell signaling, cardiomyocyte contractility measurements Biochemical and biophysical research communications Medium 31604529
2020 GRK2 and GRK3 are both required for mu-opioid receptor beta-arrestin2 recruitment and internalization; CRISPR/Cas9 double knockout of GRK2/3 substantially reduced agonist-induced MOR internalization and beta-arrestin2 recruitment, with GRK2 contributing more than GRK3; rescue expression of each GRK restored respective functions. CRISPR/Cas9 knockout (GRK2-KO, GRK3-KO, double KO), rescue expression, BRET beta-arrestin2 recruitment assay, FACS-based MOR internalization assay, pharmacological inhibition (CMPD101) Scientific reports High 33060647
2020 GRK3 is recruited to chemokine-stimulated ACKR4 prior to beta-arrestins and facilitates beta-arrestin recruitment; GRK2/3 inhibition partially reduced steady-state and chemokine-driven beta-arrestin interaction with ACKR4; beta-arrestin overexpression accelerated ACKR4-mediated CCL19 uptake. Bioluminescence resonance energy transfer (BRET) for GRK and beta-arrestin recruitment kinetics, GRK2/3 pharmacological inhibition, beta-arrestin CRISPR knockout cells, fluorescent chemokine internalization assays Frontiers in immunology Medium 32391018
2023 GRK3 phosphorylates HDAC2 at serine-394, enhancing HDAC2's epigenetic repression of anti-angiogenic factor Thrombospondin-1 (TSP1) and NE-repressor REST, thereby promoting neuroendocrine differentiation and angiogenesis in prostate cancer cells; this pathway is activated by androgen deprivation and hypoxia. Co-immunoprecipitation (GRK3-HDAC2), phosphorylation site identification (S394), GRK3/HDAC2 overexpression and knockdown, REST and TSP1 reporter/ChIP assays, in vitro and in vivo functional assays Cancer letters Medium 37543278
2024 Gβ5 selectively activates GRK3 (but not GRK2) at the mu-opioid receptor; GRK3 is recruited to the plasma membrane by both Gβ1 and Gβ5 upon MOR stimulation, but Gβ5 acts through confined membrane domains in a freely diffusible GRK3 state; this Gαz-Gβ5-GRK3 axis is selectively engaged by the biased agonist oliceridine. Genome-edited cell lines (multiple GRK and Gβ knockouts), BRET functional assays, single-molecule imaging, particle diffusion analysis, pharmacological profiling European journal of pharmacology High 39579957
2024 GRK3 plays a general role in platelet GPCR desensitization; GRK3-knockout platelets show potentiated aggregation and dense granule secretion in response to multiple GPCR agonists (2-MeSADP, U46619, thrombin, AYPGKF, serotonin+epinephrine costimulation) but not to collagen (non-GPCR), with enhanced AKT and ERK phosphorylation; GRK3-KO mice have shorter tail bleeding times. GRK3 knockout mice, platelet aggregation assays, dense granule secretion assays, phospho-AKT/ERK Western blot, tail bleeding time assay, second-challenge agonist re-stimulation paradigm Thrombosis and haemostasis High 39419098
2021 GRK3 deficiency in mice leads to elevated brain IL-1β, increased kynurenic acid (KYNA) turnover, hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disrupted prepulse inhibition, linking GRK3 to immunomodulatory and dopaminergic signaling relevant to psychosis. Grk3-/- mice, behavioral assays (PPI, amphetamine sensitization), electrophysiology (dopamine neuron firing), biochemical measurements (IL-1β, KYNA), molecular imaging Molecular psychiatry Medium 33976392
1994 The human ADRBK2 (GRK3) gene was mapped by FISH to chromosome 22q11. Fluorescence in situ hybridization (FISH) Genomics Low 7695743

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. The Journal of biological chemistry 204 16648139
2009 The c-terminus of GRK3 indicates rapid dissociation of G protein heterotrimers. Cellular signalling 147 19258039
1997 G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization. The Journal of biological chemistry 129 9325250
2008 Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling. The Journal of clinical investigation 109 18274673
2003 G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not opioid withdrawal. British journal of pharmacology 85 14662727
2006 Mu opioid receptor activation of ERK1/2 is GRK3 and arrestin dependent in striatal neurons. The Journal of biological chemistry 65 16982618
2005 ATP stimulates GRK-3 phosphorylation and beta-arrestin-2-dependent internalization of P2X7 receptor. American journal of physiology. Cell physiology 59 15728711
1998 Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs. The American journal of physiology 52 9746479
2001 GRK3 mediates desensitization of CRF1 receptors: a potential mechanism regulating stress adaptation. American journal of physiology. Regulatory, integrative and comparative physiology 46 11247813
2020 ACKR4 Recruits GRK3 Prior to β-Arrestins but Can Scavenge Chemokines in the Absence of β-Arrestins. Frontiers in immunology 45 32391018
2020 Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells. Scientific reports 45 33060647
2016 GRK3 is a direct target of CREB activation and regulates neuroendocrine differentiation of prostate cancer cells. Oncotarget 41 27191986
1994 Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes. Genomics 41 7695743
2014 GRK3 is essential for metastatic cells and promotes prostate tumor progression. Proceedings of the National Academy of Sciences of the United States of America 37 24434559
2002 GRK3 regulation during CRF- and urocortin-induced CRF1 receptor desensitization. Biochemical and biophysical research communications 35 12413940
2007 Cardiac-restricted expression of the carboxyl-terminal fragment of GRK3 Uncovers Distinct Functions of GRK3 in regulation of cardiac contractility and growth: GRK3 controls cardiac alpha1-adrenergic receptor responsiveness. The Journal of biological chemistry 30 18165681
2010 beta-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion. Journal of hypertension 24 20216086
2011 Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: a potential link to stress resilience. Behavioural brain research 23 21333691
2006 Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex. Biological psychiatry 20 16697355
2015 GRK3 suppresses L-DOPA-induced dyskinesia in the rat model of Parkinson's disease via its RGS homology domain. Scientific reports 17 26043205
2007 Further evidence for association of GRK3 to bipolar disorder suggests a second disease mutation. Psychiatric genetics 17 18075471
2003 Desensitization of alpha 2A-adrenoceptor signalling by modest levels of adrenaline is facilitated by beta 2-adrenoceptor-dependent GRK3 up-regulation. British journal of pharmacology 17 12642394
2019 Pharmacological antagonism of histamine H2R ameliorated L-DOPA-induced dyskinesia via normalization of GRK3 and by suppressing FosB and ERK in PD. Neurobiology of aging 16 31306812
2009 Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients. The international journal of neuropsychopharmacology 13 19400979
2007 Activation of the CRF(1) receptor causes ERK1/2 mediated increase in GRK3 expression in CATH.a cells. FEBS letters 12 17583697
2006 Bipolar 1 disorder is not associated with the RGS4, PRODH, COMT and GRK3 genes. Psychiatric genetics 12 17106420
2021 GRK3 deficiency elicits brain immune activation and psychosis. Molecular psychiatry 11 33976392
2011 Activity of β2-adrenergic receptor in oral squamous cell carcinoma is mediated by overexpression of the ADRBK2 gene: a pilot study. Biotechnic & histochemistry : official publication of the Biological Stain Commission 10 21916780
2023 A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression. Cancer letters 9 37543278
2019 The N-termini of GRK2 and GRK3 simulate the stimulating effects of RKIP on β-adrenoceptors. Biochemical and biophysical research communications 8 31604529
2009 Allele specific analysis of the ADRBK2 gene in lymphoblastoid cells from bipolar disorder patients. Journal of psychiatric research 8 19766236
2005 Lymphocyte G-protein receptor kinase (GRK)3 mRNA levels in bipolar disorder. The international journal of neuropsychopharmacology 8 16359584
2024 TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells. Cancer gene therapy 7 38714850
2023 TEAD3 inhibits the proliferation and metastasis of prostate cancer via suppressing ADRBK2. Biochemical and biophysical research communications 6 36907139
2007 Association analysis of GRK3 gene promoter variants in cocaine abuse. Psychiatric genetics 5 17621168
2024 Signal profiles and spatial regulation of β-arrestin recruitment through Gβ5 and GRK3 at the μ-opioid receptor. European journal of pharmacology 2 39579957
2023 Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget's Disease of Bone. Cells 1 37048054
2024 Distinct Role of GRK3 in Platelet Activation by Desensitization of G Protein-Coupled Receptors. Thrombosis and haemostasis 0 39419098
2018 G Protein-Coupled Receptor Kinase 3 (GRK3) in Olfaction. Methods in molecular biology (Clifton, N.J.) 0 29884935
2007 Regulatory mechanisms underlying GKR2 levels in U937 cells: evidence for GRK3 involvement. Biochemical pharmacology 0 17433264

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