Gene Symbol: Grk3
Description: G protein-coupled receptor kinase 3
Alias: Adrbk2, beta-adrenergic receptor kinase 2, adrenergic receptor kinase, beta 2 (G-protein-linked receptor kinase), adrenergic, beta, receptor kinase 2, beta ARK2, beta-ARK-2
Species: rat
Products:     Grk3

Top Publications

  1. Dent M, Tappia P, Dhalla N. Gender differences in ?-adrenoceptor system in cardiac hypertrophy due to arteriovenous fistula. J Cell Physiol. 2011;226:181-6 pubmed publisher
    ..Although GRK2 gene expression was increased in both sexes, an increase in GRK3 mRNA was seen only in AV shunt female rats...
  2. Salim S, Hite B, Eikenburg D. Activation of the CRF(1) receptor causes ERK1/2 mediated increase in GRK3 expression in CATH.a cells. FEBS Lett. 2007;581:3204-10 pubmed
    G-protein coupled receptor kinase 3 (GRK3) mediates desensitization of alpha(2)-adrenergic (alpha(2)-AR) and CRF(1) receptors...
  3. Vinge L, Andressen K, Attramadal T, Andersen G, Ahmed M, Peppel K, et al. Substrate specificities of g protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function. Mol Pharmacol. 2007;72:582-91 pubmed
    The closely related G protein-coupled receptor kinases GRK2 and GRK3 are both expressed in cardiac myocytes...
  4. Schutzer W, Reed J, Bliziotes M, Mader S. Upregulation of G protein-linked receptor kinases with advancing age in rat aorta. Am J Physiol Regul Integr Comp Physiol. 2001;280:R897-903 pubmed
    ..This increase likely results in enhanced phosphorylation and desensitization of beta-ARs. These biochemical changes are consistent with observed aging physiology...
  5. Benovic J, Onorato J, Arriza J, Stone W, Lohse M, Jenkins N, et al. Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. J Biol Chem. 1991;266:14939-46 pubmed
    ..a bovine brain cDNA library we have isolated a clone encoding a beta ARK-related enzyme which we have termed beta ARK2. Overall, this enzyme has 85% amino acid identity with beta ARK, with the protein kinase catalytic domain having ..
  6. Hillhouse E, Grammatopoulos D. The molecular mechanisms underlying the regulation of the biological activity of corticotropin-releasing hormone receptors: implications for physiology and pathophysiology. Endocr Rev. 2006;27:260-86 pubmed
    ..The type of activating agonist, receptor, and target cell appears to play a major role in determining the overall signaling and biological responses in health and disease. ..
  7. Marion S, Robert F, Crepieux P, Martinat N, Troispoux C, Guillou F, et al. G protein-coupled receptor kinases and beta arrestins are relocalized and attenuate cyclic 3',5'-adenosine monophosphate response to follicle-stimulating hormone in rat primary Sertoli cells. Biol Reprod. 2002;66:70-6 pubmed
    ..These results highlight the relationship existing between the GRK/beta-arrestin regulatory system and the FSH-R signaling machinery in a physiological model. ..
  8. Yi X, Gerdes A, Li F. Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats. Hypertension. 2002;39:1058-63 pubmed
    ..The results suggest different roles for GRK2 and GRK5 in G-protein signaling and RNA biogenesis. Subcellular redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting from chronic hypertension. ..
  9. Taneja M, Salim S, Saha K, Happe H, Qutna N, Petty F, et al. 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. Behav Brain Res. 2011;221:25-33 pubmed publisher
    ..factor 1 receptor (CRF(1)-R) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (..

More Information


  1. Beaulieu J, Gainetdinov R. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011;63:182-217 pubmed publisher
  2. Sedaghat K, Tiberi M. Cytoplasmic tail of D1 dopaminergic receptor differentially regulates desensitization and phosphorylation by G protein-coupled receptor kinase 2 and 3. Cell Signal. 2011;23:180-92 pubmed publisher
    ..Interestingly, CT truncations have no effect on the basal and DA-induced association of receptors with GRK3. Furthermore, we demonstrate that desensitization of D1R is considerably more robust in cells expressing GRK3...
  3. Arriza J, Dawson T, Simerly R, Martin L, Caron M, Snyder S, et al. The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain. J Neurosci. 1992;12:4045-55 pubmed
    ..The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron ..
  4. Menco B. The fine-structural distribution of G-protein receptor kinase 3, beta-arrestin-2, Ca2+/calmodulin-dependent protein kinase II and phosphodiesterase PDE1C2, and a Cl(-)-cotransporter in rodent olfactory epithelia. J Neurocytol. 2005;34:11-36 pubmed
    ..Is this also true for molecules of olfactory signal-termination and -regulation? G-protein receptor kinase 3 (GRK3) supposedly aids in signal desensitization at the level of odor receptors, whereas beta-arrestin-2, Ca2+/calmodulin-..
  5. Kuwasako K, Kitamura K, Nagata S, Hikosaka T, Kato J. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2. Biochem Biophys Res Commun. 2010;392:380-5 pubmed publisher
    ..Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling. ..
  6. Hejnova L, Skrabalova J, Novotny J. Prolonged Morphine Treatment Alters Expression and Plasma Membrane Distribution of ?-Adrenergic Receptors and Some Other Components of Their Signaling System in Rat Cerebral Cortex. J Mol Neurosci. 2017;63:364-376 pubmed publisher
    ..Morphine treatment resulted in a significant upregulation of ?-ARs, GRK3, and some AC isoforms (AC-I, -II, and -III)...
  7. Walensky L, Roskams A, Lefkowitz R, Snyder S, Ronnett G. Odorant receptors and desensitization proteins colocalize in mammalian sperm. Mol Med. 1995;1:130-41 pubmed
    ..conserved among odorant receptors and using fusion protein antibodies to G-protein receptor kinase 3 (GRK3/beta ARK2) and beta-arrestin2...
  8. Vinge L, Øie E, Andersson Y, Grøgaard H, Andersen G, Attramadal H. Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats. Am J Physiol Heart Circ Physiol. 2001;281:H2490-9 pubmed
    ..Myocardial GRK2, GRK5, beta-arrestin-1, and beta-arrestin-2 mRNA levels, but not that of GRK3, were induced in the failing hearts...
  9. Ahmed M, Bychkov E, Li L, Gurevich V, Gurevich E. GRK3 suppresses L-DOPA-induced dyskinesia in the rat model of Parkinson's disease via its RGS homology domain. Sci Rep. 2015;5:10920 pubmed publisher
    ..Here we demonstrate that LID is attenuated by overexpression of GRK3 in the striatum, whereas knockdown of GRK3 by microRNA exacerbated it...
  10. Tarrant T, Billard M, Timoshchenko R, McGinnis M, Serafin D, Foreman O, et al. G protein-coupled receptor kinase-3-deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses. J Leukoc Biol. 2013;94:1243-51 pubmed publisher
    ..Recently, GRK3 was identified as a negative regulator of CXCL12/CXCR4 signaling that is defective in human WHIM syndrome...
  11. Boekhoff I, Inglese J, Schleicher S, Koch W, Lefkowitz R, Breer H. Olfactory desensitization requires membrane targeting of receptor kinase mediated by beta gamma-subunits of heterotrimeric G proteins. J Biol Chem. 1994;269:37-40 pubmed the cAMP dependent protein kinase and a specialized G protein-coupled receptor kinase originally termed beta ARK2 (GRK3)...
  12. Montó F, Oliver E, Vicente D, Rueda J, Aguero J, Almenar L, et al. Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure etiology and correlates to clinical variables. Am J Physiol Heart Circ Physiol. 2012;303:H368-76 pubmed publisher
    ..the mRNA/protein expressions of six ARs (?(1A), ?(1B), ?(1D), ?(1), ?(2), and ?(3)) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), ..
  13. Arioglu E, Guner S, Ozakca I, Altan V, Ozcelikay A. The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors. Mol Cell Biochem. 2010;335:59-66 pubmed publisher
    ..other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions...
  14. Pi M, Oakley R, Gesty Palmer D, Cruickshank R, Spurney R, Luttrell L, et al. Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization. Mol Endocrinol. 2005;19:1078-87 pubmed
    ..We conclude that GRKs and beta-arrestins play key roles in regulating CASR responsiveness in parathyroid glands. ..
  15. Yi X, Zhou J, Baker J, Wang X, Gerdes A, Li F. Myocardial expression and redistribution of GRKs in hypertensive hypertrophy and failure. Anat Rec A Discov Mol Cell Evol Biol. 2005;282:13-23 pubmed
    ..In this study, we determined the expression and subcellular distribution of GRK2, GRK3, GRK5, and GRK6 in cardiac myocytes of 2- to 24-month-old spontaneously hypertensive heart failure (SHHF) rats...
  16. Hynes T, Mervine S, Yost E, Sabo J, Berlot C. Live cell imaging of Gs and the beta2-adrenergic receptor demonstrates that both alphas and beta1gamma7 internalize upon stimulation and exhibit similar trafficking patterns that differ from that of the beta2-adrenergic receptor. J Biol Chem. 2004;279:44101-12 pubmed
    ..Because Rab11 regulates traffic through recycling endosomes, co-localization of alphas and beta1gamma7 on these endosomes may indicate a means of recycling specific alphasbetagamma combinations to the plasma membrane. ..
  17. Spurney R, Flannery P, Garner S, Athirakul K, Liu S, Guilak F, et al. Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts. J Clin Invest. 2002;109:1361-71 pubmed
    ..The predominant effect of the transgene, however, was anabolic, as evidenced by an increase in bone density and trabecular bone volume in the transgenic mice compared with nontransgenic littermate controls. ..
  18. Ahmed M, Bychkov E, Gurevich V, Benovic J, Gurevich E. Altered expression and subcellular distribution of GRK subtypes in the dopamine-depleted rat basal ganglia is not normalized by l-DOPA treatment. J Neurochem. 2008;104:1622-36 pubmed
    ..The decrease in GRK proteins in globus pallidus, but not cCPu, was mirrored by reduction in mRNA. GRK3 protein was reduced in the rostral caudate-putamen (rCPu), whereas other isoforms were either unchanged or up-..
  19. Schleicher S, Boekhoff I, Arriza J, Lefkowitz R, Breer H. A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination. Proc Natl Acad Sci U S A. 1993;90:1420-4 pubmed
    ..These data suggest that a sequential interplay of second-messenger-dependent and receptor-specific kinases is functionally involved in olfactory desensitization. ..
  20. Ertley R, Bazinet R, Lee H, Rapoport S, Rao J. Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex. Biol Psychiatry. 2007;61:246-9 pubmed
    ..Chronic Li+ (24%) and CBZ (44%) significantly increased GRK3 in the membrane but not cytosol fractions. Chronic VPA had no effect on GRK3...
  21. Wang J, Liu X. A G protein-coupled receptor kinase induces Xenopus oocyte maturation. J Biol Chem. 2003;278:15809-14 pubmed
    ..test the existence and function of this putative GpCR, we utilized a mammalian G-protein-coupled receptor kinase (GRK3) and beta-arrestin-2, which together are known to cause GpCR desensitization...
  22. Shenoy S, Lefkowitz R. Angiotensin II-stimulated signaling through G proteins and beta-arrestin. Sci STKE. 2005;2005:cm14 pubmed
  23. Montó F, Oliver E, Vicente D, Buendía F, Rueda J, Agüero J, et al. β2- and β1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases. J Cardiovasc Pharmacol. 2015;66:478-86 pubmed publisher
    ..or β(2)-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal ..