GRK5

Summary

Gene Symbol: GRK5
Description: G protein-coupled receptor kinase 5
Alias: GPRK5, G protein-coupled receptor kinase 5, FP2025, g protein-coupled receptor kinase GRK5
Species: human
Products:     GRK5

Top Publications

  1. Kunapuli P, Gurevich V, Benovic J. Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5. J Biol Chem. 1994;269:10209-12 pubmed
    ..b>GRK5, a recently identified member of the GRK family, undergoes a rapid phospholipid-stimulated autophosphorylation to a ..
  2. Thiyagarajan M, Stracquatanio R, Pronin A, Evanko D, Benovic J, Wedegaertner P. A predicted amphipathic helix mediates plasma membrane localization of GRK5. J Biol Chem. 2004;279:17989-95 pubmed
    ..Previous studies demonstrated the presence of a membrane binding domain in the C terminus of GRK5. Here we define a mechanism by which this short C-terminal stretch of amino acids of GRK5 mediates PM localization...
  3. Tran T, Jorgensen R, Clark R. Phosphorylation of the beta2-adrenergic receptor in plasma membranes by intrinsic GRK5. Biochemistry. 2007;46:14438-49 pubmed
    ..washed plasma membrane fractions retained the 10-15-fold ISO stimulation of GRK site phosphorylation and GRK5 levels while being depleted of GRK2 and GRK6...
  4. Sorriento D, Ciccarelli M, Santulli G, Campanile A, Altobelli G, Cimini V, et al. The G-protein-coupled receptor kinase 5 inhibits NFkappaB transcriptional activity by inducing nuclear accumulation of IkappaB alpha. Proc Natl Acad Sci U S A. 2008;105:17818-23 pubmed publisher
    ..Indeed, GRK5 can translocate to the nucleus by means of a nuclear localization sequence, suggesting that this kinase regulates ..
  5. Cai X, Wu J, Exum S, Oppermann M, Premont R, Shenoy S, et al. Reciprocal regulation of the platelet-derived growth factor receptor-beta and G protein-coupled receptor kinase 5 by cross-phosphorylation: effects on catalysis. Mol Pharmacol. 2009;75:626-36 pubmed publisher
    ..is diminished when the PDGFRbeta is phosphorylated on seryl residues by G protein-coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFRbeta remain obscure...
  6. So C, Michal A, Mashayekhi R, Benovic J. G protein-coupled receptor kinase 5 phosphorylates nucleophosmin and regulates cell sensitivity to polo-like kinase 1 inhibition. J Biol Chem. 2012;287:17088-99 pubmed publisher
    ..Here, we attempted to identify potential nuclear substrates for GRK5. Our studies reveal that GRK5 is able to interact with and phosphorylate nucleophosmin (NPM1) both in vitro and in ..
  7. Li H, Gan W, Lu L, Dong X, Han X, Hu C, et al. A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. Diabetes. 2013;62:291-8 pubmed publisher
    ..at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3...
  8. Kunapuli P, Benovic J. Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. Proc Natl Acad Sci U S A. 1993;90:5588-92 pubmed
    ..Here we report the isolation of a cDNA that encodes a 590-amino acid protein kinase, termed GRK5, which has 34.8% and 47.2% amino acid identities with beta ARK and rhodopsin kinase, respectively...
  9. Pronin A, Carman C, Benovic J. Structure-function analysis of G protein-coupled receptor kinase-5. Role of the carboxyl terminus in kinase regulation. J Biol Chem. 1998;273:31510-8 pubmed
    ..Recent studies have revealed that the GRKs are also subject to post-translational regulation. For example, GRK5 activity is strongly inhibited by protein kinase C phosphorylation and by Ca2+-calmodulin binding...

More Information

Publications131 found, 100 shown here

  1. Johnson L, Scott M, Pitcher J. G protein-coupled receptor kinase 5 contains a DNA-binding nuclear localization sequence. Mol Cell Biol. 2004;24:10169-79 pubmed
    ..Here we report that GRK5 contains a DNA-binding nuclear localization sequence (NLS) and that its nuclear localization is regulated by GPCR ..
  2. Wang W, Mihlbachler K, Bleecker E, Weiss S, Liggett S. A polymorphism of G-protein coupled receptor kinase5 alters agonist-promoted desensitization of beta2-adrenergic receptors. Pharmacogenet Genomics. 2008;18:729-32 pubmed publisher
    ..b>GRK5 was found to be highly expressed in airway smooth muscle, the tissue target for beta-agonists...
  3. Chen M, Philipp M, Wang J, Premont R, Garrison T, Caron M, et al. G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway. J Biol Chem. 2009;284:35040-8 pubmed publisher
    ..We found that G protein-coupled receptor kinases 5 and 6 (GRK5/6), traditionally known to phosphorylate and desensitize 7TM G protein-coupled receptors, directly phosphorylate ..
  4. Baameur F, Morgan D, Yao H, Tran T, Hammitt R, Sabui S, et al. Role for the regulator of G-protein signaling homology domain of G protein-coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor and rhodopsin phosphorylation. Mol Pharmacol. 2010;77:405-15 pubmed publisher
    ..To define its function, a panel of GRK5 and -6 mutants was generated and screened by intact-cell assay of constitutive GRK phosphorylation of the beta(2)-..
  5. Chen X, Zhu H, Yuan M, Fu J, Zhou Y, Ma L. G-protein-coupled receptor kinase 5 phosphorylates p53 and inhibits DNA damage-induced apoptosis. J Biol Chem. 2010;285:12823-30 pubmed publisher
    ..Knockdown GRK5 in osteosarcoma cells inhibits DNA damage-induced apoptosis via a p53-mediated mechanism...
  6. Barker B, Benovic J. G protein-coupled receptor kinase 5 phosphorylation of hip regulates internalization of the chemokine receptor CXCR4. Biochemistry. 2011;50:6933-41 pubmed publisher
    ..An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro...
  7. Bychkov E, Ahmed M, Gurevich V, Benovic J, Gurevich E. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis. 2011;44:248-58 pubmed publisher
    ..The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder. ..
  8. Malach E, Shaul M, Peri I, Huang L, Spielman A, Seger R, et al. Membrane-permeable tastants amplify β2-adrenergic receptor signaling and delay receptor desensitization via intracellular inhibition of GRK2's kinase activity. Biochim Biophys Acta. 2015;1850:1375-88 pubmed publisher
    Amphipathic sweet and bitter tastants inhibit purified forms of the protein kinases GRK2, GRK5 and PKA activities...
  9. Serafin D, Allyn B, Sassano M, Timoshchenko R, Mattox D, Brozowski J, et al. Chemerin-activated functions of CMKLR1 are regulated by G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory macrophages. Mol Immunol. 2019;106:12-21 pubmed publisher
    ..The ubiquitously expressed GRK family members include GRK2, GRK3, GRK5, and GRK6, but it is unknown which GRK regulates CMKLR1 cellular and signaling functions...
  10. Johnson A, Hanley Yanez K, Yancy C, Taylor A, Feldman A, McNamara D. Adrenergic Polymorphisms and Survival in African Americans with Heart Failure: Results from A-HeFT. J Card Fail. 2019;: pubmed publisher
    ..The β1 adrenergic receptor (ADRB1) Arg389Gly, G-protein receptor kinase type 5 (GRK5) Gln41Leu, G-protein β-3 subunit (GNB3) 825 C/T, and α2c deletion affect adrenergic tone, impact heart failure ..
  11. Ohba Y, Nakaya M, Watari K, Nagasaka A, Kurose H. GRK6 phosphorylates IκBα at Ser(32)/Ser(36) and enhances TNF-α-induced inflammation. Biochem Biophys Res Commun. 2015;461:307-13 pubmed publisher
    ..To date, several intracellular substrates for GRK2 and GRK5 have been reported. However, those for GRK6 are poorly understood...
  12. Kohli U, Diedrich A, Kannankeril P, Muszkat M, Sofowora G, Hahn M, et al. Genetic variation in alpha2-adrenoreceptors and heart rate recovery after exercise. Physiol Genomics. 2015;47:400-6 pubmed publisher
    ..genetic variants in autonomic pathways (6 ADRA2A, 1 ADRA2B, 4 ADRA2C, 2 ADRB1, 3 ADRB2, 2 NET, 2 CHT, and 1 GRK5) on the outcomes before and after adjustment for potential confounders...
  13. Franklin J, Carrasco G. Cocaine potentiates multiple 5-HT2A receptor signaling pathways and is associated with decreased phosphorylation of 5-HT2A receptors in vivo. J Mol Neurosci. 2015;55:770-7 pubmed publisher
    ..This phenomenon was associated with reduced levels of G-protein receptor kinase 5 (GRK5), but not GRK2 or RSK2, proteins...
  14. Arraes S, Freitas M, da Silva S, de Paula Neto H, Alves Filho J, Auxiliadora Martins M, et al. Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation. Blood. 2006;108:2906-13 pubmed
    ..High expression of G protein-coupled receptor kinase 2 (GRK2) and GRK5 was detected in septic neutrophils and control cells treated with cytokines plus LPS...
  15. Li L, Homan K, Vishnivetskiy S, Manglik A, Tesmer J, Gurevich V, et al. G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs). J Biol Chem. 2015;290:10775-90 pubmed publisher
    ..Here, we show that although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of several GPCRs, including β2-adrenergic and M2 muscarinic receptors,..
  16. Figtree G, Bagnall R, Abdulla I, Buchholz S, Galougahi K, Yan W, et al. No association of G-protein-coupled receptor kinase 5 or β-adrenergic receptor polymorphisms with Takotsubo cardiomyopathy in a large Australian cohort. Eur J Heart Fail. 2013;15:730-3 pubmed publisher
    ..small studies have reported association of TC with functional variants in the G-protein-coupled receptor kinase 5 (GRK5) gene, as well as in the β1-adrenergic receptor (β1AR) and β2AR...
  17. Shahpasandzadeh H, Popova B, Kleinknecht A, Fraser P, Outeiro T, Braus G. Interplay between sumoylation and phosphorylation for protection against α-synuclein inclusions. J Biol Chem. 2014;289:31224-40 pubmed publisher
    ..sumoylation could be suppressed by serine 129 phosphorylation by the human G protein-coupled receptor kinase 5 (GRK5) in yeast...
  18. Hullmann J, Grisanti L, Makarewich C, Gao E, Gold J, Chuprun J, et al. GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity. Circ Res. 2014;115:976-85 pubmed publisher
    ..Both GRK2 and GRK5, the predominant GRKs expressed in the heart, have been shown to be upregulated in failing human myocardium...
  19. Do D, Strathe A, Ostersen T, Pant S, Kadarmideen H. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake. Front Genet. 2014;5:307 pubmed publisher
    ..29 (TTC29),suppressor of glucose, autophagy associated 1 (SOGA1),MAS1,G-protein-coupled receptor (GPCR) kinase 5 (GRK5),prospero-homeobox protein 1 (PROX1),GPCR 155 (GPR155), and FYVE domain containing the 26 (ZFYVE26) were identified ..
  20. Homan K, Wu E, Cannavo A, Koch W, Tesmer J. Identification and characterization of amlexanox as a G protein-coupled receptor kinase 5 inhibitor. Molecules. 2014;19:16937-49 pubmed publisher
    ..Far fewer selective inhibitors have been reported for GRK5, a target for the treatment of cardiac hypertrophy, and the mechanism of action of reported compounds is unknown...
  21. Shang Z, Han F, Zhou X, Bao Z, Zhu J, Wang T, et al. A variant of GRK5 is associated with the therapeutic efficacy of repaglinide in Chinese Han patients with type 2 diabetes mellitus. Drug Dev Res. 2018;79:129-135 pubmed publisher
    Post-Market Research We aimed to investigate the impact of G protein-coupled receptor kinase 5 (GRK5) rs10886471 polymorphism on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM)...
  22. Oda T, Yamamoto T, Kato T, Uchinoumi H, Fukui G, Hamada Y, et al. Nuclear translocation of calmodulin in pathological cardiac hypertrophy originates from ryanodine receptor bound calmodulin. J Mol Cell Cardiol. 2018;125:87-97 pubmed publisher
    ..CaM lacks a nuclear localization signal (NLS), but G-protein coupled receptor kinase 5 (GRK5) binds CaM, has a NLS and translocates like CaM in response to AngII or PE...
  23. Bouley R, Waldschmidt H, Cato M, Cannavo A, Song J, Cheung J, et al. Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors. Mol Pharmacol. 2017;92:707-717 pubmed publisher
    ..GRK2 and GRK5 are overexpressed in the failing heart and thus have become therapeutic targets...
  24. 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
    ..There was no change in quantity of G proteins and some other signaling molecules (AC-IV, AC-V/VI, GRK2, GRK5, GRK6, and ?-arrestin) compared with controls...
  25. Yeh S, Zambrano C, Koch W, Purcell N. PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) regulates G-protein-coupled receptor kinase 5 (GRK5)-induced cardiac hypertrophy in vitro. J Biol Chem. 2018;293:8056-8064 pubmed publisher
    ..G-protein-coupled receptor kinase 5 (GRK5) is an AGC kinase that regulates phenylephrine (PE)-induced cardiac hypertrophy through its noncanonical function ..
  26. Rodríguez Serrano M, Rueda Soriano J, Buendía Fuentes F, Osa Sáez A, Montó Guillot F, D Ocon Navaza P, et al. Changes in Adrenoceptor and GRK Expression in Patients With Chronic Pulmonary Regurgitation. Rev Esp Cardiol (Engl Ed). 2018;: pubmed publisher
    ..Lymphocyte expression of adrenoceptors (?1 and ?2) and kinases (GRK2, GRK3, and GRK5) reflects the neurohumoral changes that occur in heart failure (HF)...
  27. Dellon E, Selitsky S, Genta R, Lash R, Parker J. Gene expression-phenotype associations in adults with eosinophilic esophagitis. Dig Liver Dis. 2018;50:804-811 pubmed publisher
    ..01). Genes associated with esophageal narrowing included CCL26 (q-value=0.028), ALOX15 (q=0.011), GRK5 (q=0.029), CPA3 (q=0.012), and TRIM2 (q=0.0027). TRIM2 was also associated with the fibrostenotic phenotype (q=0...
  28. Sorriento D, Santulli G, Ciccarelli M, Maione A, Illario M, Trimarco B, et al. The Amino-Terminal Domain of GRK5 Inhibits Cardiac Hypertrophy through the Regulation of Calcium-Calmodulin Dependent Transcription Factors. Int J Mol Sci. 2018;19: pubmed publisher
    We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NF?B activity in cardiac cells leading to a significant amelioration of LVH...
  29. Mushegian A, Gurevich V, Gurevich E. The origin and evolution of G protein-coupled receptor kinases. PLoS ONE. 2012;7:e33806 pubmed publisher
    ..one including GRK2 and GRK3, and the other consisting of all remaining GRKs, split into GRK1-GRK7 lineage and GRK4-GRK5-GRK6 lineage in vertebrates...
  30. Zhang Y, Shen G, Shangguan L, Yu Y, He M. Involvement of NFκB signaling in mediating the effects of GRK5 on neural stem cells. Brain Res. 2015;1608:31-9 pubmed publisher
    ..G protein-coupled receptor kinase 5 (GRK5) can protect neurons from degeneration...
  31. Lutz S, Falcenberg M, Machicao F, Peter A, Kächele M, Randrianarisoa E, et al. Single Nucleotide Polymorphisms in the G-Protein Coupled Receptor Kinase 5 (GRK5) Gene are associated with Plasma LDL-Cholesterol Levels in Humans. Sci Rep. 2018;8:7745 pubmed publisher
    Genetically modified mice models suggest an important role for G-protein-coupled receptor kinase 5 (GRK5) in the pathophysiology of obesity and related disorders...
  32. Daniele S, Trincavelli M, Fumagalli M, Zappelli E, Lecca D, Bonfanti E, et al. Does GRK-? arrestin machinery work as a "switch on" for GPR17-mediated activation of intracellular signaling pathways?. Cell Signal. 2014;26:1310-25 pubmed publisher
    ..On the other hand, purinergic ligand exclusively recruited the GRK5 subtype, and induced, via a G protein-independent/?-arrestin-dependent mechanism, a receptor/?-arrestin stable ..
  33. Nash C, Nelson C, Mistry R, Moeller Olsen C, Christofidou E, Challiss R, et al. Differential regulation of β2-adrenoceptor and adenosine A2B receptor signalling by GRK and arrestin proteins in arterial smooth muscle. Cell Signal. 2018;51:86-98 pubmed publisher
    ..GRK2 or GRK5 depletion enhanced and prolonged β2AR/AC signalling, while combined deletion of GRK2/5 has an additive ..
  34. Kim J, Chakraborty P, Wang Z, Daaka Y. G-protein coupled receptor kinase 5 regulates prostate tumor growth. J Urol. 2012;187:322-9 pubmed publisher
    ..Western blot analysis to determine GRK expression in prostate cancer and RNA interference to establish the role of GRK5 in prostate cancer growth and progression through the cell cycle...
  35. Homan K, Waldschmidt H, Glukhova A, Cannavo A, Song J, Cheung J, et al. Crystal Structure of G Protein-coupled Receptor Kinase 5 in Complex with a Rationally Designed Inhibitor. J Biol Chem. 2015;290:20649-59 pubmed publisher
    ..The two most widely expressed GRKs (GRK2 and GRK5) play a role in cardiovascular disease and thus represent important targets for the development of novel ..
  36. Nanjidsuren T, Park C, Sim B, Kim S, Chang K, Kang M, et al. GRK5-Knockout Mice Generated by TALEN-Mediated Gene Targeting. Anim Biotechnol. 2016;27:223-30 pubmed publisher
    ..TALEN vectors were designed to target exons 1, 3, and 5 of the mouse GRK5 gene. Flow cytometry showed that the activity of the TALEN mRNAs targeted to exons 1, 3, and 5 was 8.7%, 9...
  37. Homan K, Larimore K, Elkins J, Szklarz M, Knapp S, Tesmer J. Identification and structure-function analysis of subfamily selective G protein-coupled receptor kinase inhibitors. ACS Chem Biol. 2015;10:310-9 pubmed publisher
    ..kinase inhibitors that could increase the melting points of the two most ubiquitously expressed GRKs: GRK2 and GRK5. Enzymatic assays on 14 of the most stabilizing hits revealed that three exhibit nanomolar potency of inhibition ..
  38. Johnson L, Robinson J, Lester K, Pitcher J. Distinct structural features of G protein-coupled receptor kinase 5 (GRK5) regulate its nuclear localization and DNA-binding ability. PLoS ONE. 2013;8:e62508 pubmed publisher
    ..In addition to this role at the plasma membrane, a nuclear function for GRK5, a member of the GRK4 subfamily of GRKs, has been reported...
  39. Zhou R, Pesant S, Cohn H, Soltys S, Koch W, Eckhart A. Negative regulation of VEGF signaling in human coronary artery endothelial cells by G protein-coupled receptor kinase 5. Clin Transl Sci. 2009;2:57-61 pubmed publisher
    G protein-coupled receptor kinase 5 (GRK5) is present in endothelial cells (ECs) and has the potential to regulate EC function through seven transmembrane-spanning receptor (7TMR) signaling...
  40. Yao X, Cato M, Labudde E, Beyett T, Tesmer J, Grant B. Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation. J Biol Chem. 2017;292:16032-16043 pubmed publisher
    ..By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both in silico and in vitro experiments that perturbation ..
  41. Bullrich F, Druck T, Kunapuli P, Gomez J, Gripp K, Schlegelberger B, et al. Chromosomal mapping of the genes GPRK5 and GPRK6 encoding G protein-coupled receptor kinases GRK5 and GRK6. Cytogenet Cell Genet. 1995;70:250-4 pubmed
    ..Chromosomal mapping of the human genes for the two most recently identified members of the GRK family, GRK5 (GPRK5) and GRK6 (GPRK6), was accomplished by correlation of the presence of the GPRK5 and GPRK6 loci with specific ..
  42. Parameswaran N, Pao C, Leonhard K, Kang D, Kratz M, Ley S, et al. Arrestin-2 and G protein-coupled receptor kinase 5 interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages. J Biol Chem. 2006;281:34159-70 pubmed
    ..Here, we demonstrate that arrestin-2 and GRK5 (G protein-coupled receptor kinase 5), proteins that regulate G protein-coupled receptor signaling, play a negative ..
  43. Lessel D, Muhammad T, Casar Tena T, Moepps B, Burkhalter M, Hitz M, et al. The analysis of heterotaxy patients reveals new loss-of-function variants of GRK5. Sci Rep. 2016;6:33231 pubmed publisher
    G protein-coupled receptor kinase 5 (GRK5) is a regulator of cardiac performance and a potential therapeutic target in heart failure in the adult...
  44. Cresci S, Kelly R, Cappola T, Diwan A, Dries D, Kardia S, et al. Clinical and genetic modifiers of long-term survival in heart failure. J Am Coll Cardiol. 2009;54:432-44 pubmed publisher
    ..Each was genotyped for beta1-adrenergic receptor (ADRB1) Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent among African Americans than Caucasians...
  45. Grotegut C, Mao L, Pierce S, Swamy G, Heine R, Murtha A. Enhanced Uterine Contractility and Stillbirth in Mice Lacking G Protein-Coupled Receptor Kinase 6 (GRK6): Implications for Oxytocin Receptor Desensitization. Mol Endocrinol. 2016;30:455-68 pubmed publisher
    ..of enhanced uterine contractility during both spontaneous and oxytocin-induced labor compared with wild-type or GRK5 knockout mice. In addition, the observed enhanced contractility was associated with high rates of term stillbirth...
  46. Franco A, Zhang L, Matkovich S, Kovacs A, Dorn G. G-protein receptor kinases 2, 5 and 6 redundantly modulate Smoothened-GATA transcriptional crosstalk in fetal mouse hearts. J Mol Cell Cardiol. 2018;121:60-68 pubmed publisher
    ..on fetal heart development by creating mice and cultured murine embryonic fibroblasts (MEFs) having floxed GRK2 and GRK5 alleles on the GRK6 null background; simultaneous conditional deletion of these 3 GRK genes was achieved using Nkx2-..
  47. 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...
  48. Kertai M, Li Y, Li Y, Shah S, Kraus W, Fontes M, et al. G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving ?-blockers. Circ Cardiovasc Genet. 2014;7:625-633 pubmed publisher
    ..Of the 492 SNPs examined, 4 intronic SNPs of the G protein-coupled kinase 5 (GRK5) gene were significantly associated with postoperative AF despite perioperative BB therapy in the discovery cohort ..
  49. Nicoletti G, De Luca V, Tarantino P, Gagliardi M, Iannello G, Novellino F, et al. Role of G-protein coupled receptor kinase 5 gene in cognitive impairment in Parkinson's disease. Psychiatry Res. 2015;230:975-7 pubmed publisher
    ..with Parkinson's disease (PD), we investigated two polymorphisms within the G-protein coupled receptor kinase 5 (GRK5) gene (rs2420616, rs4752293) to determine a possible risk factor for dementia...
  50. Dou H, Wang Y, Yang N, Heng M, Zhou X, Bu H, et al. Association between genetic variants and characteristic symptoms of type 2 diabetes: A matched case-control study. Chin J Integr Med. 2017;23:415-424 pubmed publisher
    ..study was performed to investigate the association between common variants in four genes (CDKAL1, GLIS3, GRK5, and TCF7L2) and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects...
  51. Penela P. Chapter Three - Ubiquitination and Protein Turnover of G-Protein-Coupled Receptor Kinases in GPCR Signaling and Cellular Regulation. Prog Mol Biol Transl Sci. 2016;141:85-140 pubmed publisher
    ..Altered expression of GRKs (particularly of GRK2 and GRK5) occurs during pathological conditions characterized by impaired GPCR signaling including inflammatory syndromes, ..
  52. Mattsson E, Saliba Gustafsson P, Ehrenborg E, Tornvall P. Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study. BMC Med Genet. 2018;19:39 pubmed publisher
    ..associations between three different loci; the β1-adrenic receptor (ADRB1), G-protein-coupled receptor kinase 5 (GRK5), Bcl-associated athanogene 3 (BAG3) and TCM but no consensus has been reached...
  53. He M, Singh P, Cheng S, Zhang Q, Peng W, Ding X, et al. GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability. Sci Rep. 2016;6:26116 pubmed publisher
    ..over-express the Swedish mutant human β-amyloid precursor protein gene with G protein-coupled receptor kinase-5 (GRK5) knockout mice...
  54. Jiang L, Fan S, Xiong Q, Zhou Y, Yang Z, Li G, et al. GRK5 functions as an oncogenic factor in non-small-cell lung cancer. Cell Death Dis. 2018;9:295 pubmed publisher
    ..G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions ..
  55. Suo W, Li L. Dysfunction of G protein-coupled receptor kinases in Alzheimer's disease. ScientificWorldJournal. 2010;10:1667-78 pubmed publisher
    ..Recent studies have indicated the possible involvement of GRK, primarily GRK2 and GRK5, dysfunction in the pathogenesis of AD...
  56. Singh H, Rajeswari M. Role of long purine stretches in controlling the expression of genes associated with neurological disorders. Gene. 2015;572:175-83 pubmed publisher
    ..identified four PR-genes in signaling pathways whose dysregulation is correlated directly with pathogenesis: GRK5 and KLK6 in Alzheimer's disease; FGF14 in craniosynostosis, mental retardation and FLT1 in neuroferritinopathy...
  57. Singh P, Peng W, Zhang Q, Ding X, Suo W. GRK5 deficiency leads to susceptibility to intermittent hypoxia-induced cognitive impairment. Behav Brain Res. 2016;302:29-34 pubmed publisher
    ..G protein-coupled receptor kinase-5 (GRK5) deficiency is recently found to render subjects more susceptible to cognitive impairment triggered by over-..
  58. Kuwasako K, Sekiguchi T, Nagata S, Jiang D, Hayashi H, Murakami M, et al. Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor. Biochem Biophys Res Commun. 2016;470:894-9 pubmed publisher
    ..Flow cytometric analysis revealed that when coexpressed with GRK4 or GRK5, the cell surface expression of the AM1 receptor was markedly decreased prior to stimulation with AM, thereby ..
  59. Yang J, Shen Z, Jiang X, Yang H, Huang H, Jin L, et al. Agonist-Activated Bombyx Corazonin Receptor Is Internalized via an Arrestin-Dependent and Clathrin-Independent Pathway. Biochemistry. 2016;55:3874-87 pubmed publisher
    ..Assays using RNA interference revealed that both GRK2 and GRK5 were essentially involved in the regulation of BmCrzR phosphorylation and internalization...
  60. Smith J, Alagesan P, Desai N, Pack T, Wu J, Inoue A, et al. C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways. Mol Pharmacol. 2017;92:136-150 pubmed publisher
    ..i>?arr2 recruitment to CXCR3A was attenuated by both G protein receptor kinase (GRK) 2/3 and GRK5/6 knockdown, while only GRK2/3 knockdown blunted recruitment to CXCR3B...
  61. Brenninkmeijer C, Price S, Lopez Bernal A, Phaneuf S. Expression of G-protein-coupled receptor kinases in pregnant term and non-pregnant human myometrium. J Endocrinol. 1999;162:401-8 pubmed
    ..Further work is necessary to determine whether GRKs and receptor desensitisation play a role in disorders of uterine contractility. ..
  62. Pronin A, Morris A, Surguchov A, Benovic J. Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem. 2000;275:26515-22 pubmed
    ..all synucleins are GRK substrates, with GRK2 preferentially phosphorylating the alpha and beta isoforms, whereas GRK5 prefers alpha-synuclein as a substrate...
  63. Liu L, Zhang L, Liu M, Zhang Y, Han X, Zhang Z. GRK5 Polymorphisms and Postoperative Atrial Fibrillation following Coronary Artery Bypass Graft Surgery. Sci Rep. 2015;5:12768 pubmed publisher
    ..After adjustment for clinical predictors of POAF, two variants in GRK5 gene (rs4752292, and rs11198893) were replicated with significance were replicated in the validation cohort...
  64. Cannavo A, Liccardo D, Eguchi A, Elliott K, Traynham C, Ibetti J, et al. Myocardial pathology induced by aldosterone is dependent on non-canonical activities of G protein-coupled receptor kinases. Nat Commun. 2016;7:10877 pubmed publisher
    ..myocardial signalling mediated by mitochondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action...
  65. Komolov K, Du Y, Duc N, Betz R, Rodrigues J, Leib R, et al. Structural and Functional Analysis of a β2-Adrenergic Receptor Complex with GRK5. Cell. 2017;169:407-421.e16 pubmed publisher
    ..MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR)...
  66. Kondrashov A, Duc Hoang M, Smith J, Bhagwan J, Duncan G, Mosqueira D, et al. Simplified Footprint-Free Cas9/CRISPR Editing of Cardiac-Associated Genes in Human Pluripotent Stem Cells. Stem Cells Dev. 2018;27:391-404 pubmed publisher
    ..Success was shown across four cardiac-associated loci (ADRB2, GRK5, RYR2, and ACTC1) by genomic cleavage and editing efficiencies of 8%-93% and 8%-67%, respectively, including mono- ..
  67. Jorgensen R, Holliday N, Hansen J, Vrecl M, Heding A, Schwartz T, et al. Characterization of G-protein coupled receptor kinase interaction with the neurokinin-1 receptor using bioluminescence resonance energy transfer. Mol Pharmacol. 2008;73:349-58 pubmed
    ..bioluminescence resonance energy transfer(2) (BRET(2)) measurements between the family A NK-1 receptor and GRK2 and GRK5 as well as their respective kinase-inactive mutants...
  68. Tarantino P, De Marco E, Annesi G, Rocca F, Annesi F, Civitelli D, et al. Lack of association between G-protein coupled receptor kinase 5 gene and Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:104-7 pubmed publisher
    ..G-protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate ?-synuclein in vitro, enhancing the ?-synuclein toxicity to dopaminergic ..
  69. Lowe J, Sanderson H, Cooke A, Ostovar M, Tsisanova E, Withey S, et al. Role of G Protein-Coupled Receptor Kinases 2 and 3 in μ-Opioid Receptor Desensitization and Internalization. Mol Pharmacol. 2015;88:347-56 pubmed publisher
    ..Inhibition of extracellular signal-regulated kinase 1/2, protein kinase C, c-Jun N-terminal kinase, or GRK5 did not inhibit the Cmpd101-insensitive component of desensitization...
  70. 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
    ..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 models of ..
  71. Traynham C, Hullmann J, Koch W. "Canonical and non-canonical actions of GRK5 in the heart". J Mol Cell Cardiol. 2016;92:196-202 pubmed publisher
    ..Over the last 20years, the role of GRK2 in HF has been widely studied. However, until recently, the role of GRK5 in cardiac pathophysiology had yet to be elucidated...
  72. Packiriswamy N, Steury M, McCabe I, Fitzgerald S, Parameswaran N. Bacterial Dose-Dependent Role of G Protein-Coupled Receptor Kinase 5 in Escherichia coli-Induced Pneumonia. Infect Immun. 2016;84:1633-1641 pubmed publisher
    G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to mediate polymicrobial sepsis-induced inflammation...
  73. Hullmann J, Traynham C, Coleman R, Koch W. The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development. Pharmacol Res. 2016;110:52-64 pubmed publisher
    ..Over the last 20 years, both GRK2 and GRK5 have been demonstrated to be critical mediators of the molecular alterations that occur in the failing heart...
  74. Park C, Lee J, Lee M, Lee J, Lee B, Oh K. A novel role of G protein-coupled receptor kinase 5 in urotensin II-stimulated cellular hypertrophy in H9c2UT cells. Mol Cell Biochem. 2016;422:151-160 pubmed
    ..factor ?B (NF-?B) translocation, both of which are predominantly mediated by G protein-coupled receptor kinase 5 (GRK5)...
  75. Polimanti R, Zhao H, Farrer L, Kranzler H, Gelernter J. Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors. Am J Med Genet B Neuropsychiatr Genet. 2017;174:846-853 pubmed publisher
    ..52*10-8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p?=?1.25*10-9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p?=?4...
  76. Menard L, Ferguson S, Barak L, Bertrand L, Premont R, Colapietro A, et al. Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration. Biochemistry. 1996;35:4155-60 pubmed
    ..Our results demonstrate that phosphorylation per se, but not the interaction with a specific GRK, is required to facilitate beta2AR sequestration. ..
  77. Sallese M, Mariggio S, Collodel G, Moretti E, Piomboni P, Baccetti B, et al. G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells. J Biol Chem. 1997;272:10188-95 pubmed
  78. Haeseleer F, Sokal I, Verlinde C, Erdjument Bromage H, Tempst P, Pronin A, et al. Five members of a novel Ca(2+)-binding protein (CABP) subfamily with similarity to calmodulin. J Biol Chem. 2000;275:1247-60 pubmed
    ..These data suggest that these novel CaBPs are an important component of Ca(2+)-mediated cellular signal transduction in the central nervous system where they may augment or substitute for CaM. ..
  79. Liggett S, Cresci S, Kelly R, Syed F, Matkovich S, Hahn H, et al. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nat Med. 2008;14:510-7 pubmed publisher
    ..Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, common in African Americans, in which leucine is substituted for ..
  80. Kurnik D, Cunningham A, Sofowora G, Kohli U, Li C, Friedman E, et al. GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans. Pharmacogenomics. 2009;10:1581-7 pubmed publisher
    A common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes a gain-of-function enzyme that enhances desensitization of the beta(1)-adrenergic receptor...
  81. Chakraborty P, Zhang Y, Coomes A, Kim W, Stupay R, Lynch L, et al. G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer. Cancer Res. 2014;74:3489-500 pubmed publisher
    ..Here, we report an important contributory role for GRK5 in human prostate cancer...
  82. Funk A, Haroutunian V, Meador Woodruff J, McCullumsmith R. Increased G protein-coupled receptor kinase (GRK) expression in the anterior cingulate cortex in schizophrenia. Schizophr Res. 2014;159:130-5 pubmed publisher
    ..untreated rats (n=10 for both). We found increased levels of GRK5 in schizophrenia...
  83. Komolov K, Bhardwaj A, Benovic J. Atomic Structure of GRK5 Reveals Distinct Structural Features Novel for G Protein-coupled Receptor Kinases. J Biol Chem. 2015;290:20629-47 pubmed publisher
    ..One member of the family, GRK5, has been implicated in several human pathologies, including heart failure, hypertension, cancer, diabetes, and ..
  84. DeRita R, Zerlanko B, Singh A, Lu H, Iozzo R, Benovic J, et al. c-Src, Insulin-Like Growth Factor I Receptor, G-Protein-Coupled Receptor Kinases and Focal Adhesion Kinase are Enriched Into Prostate Cancer Cell Exosomes. J Cell Biochem. 2017;118:66-73 pubmed publisher
    ..J. Cell. Biochem. 118: 66-73, 2017. © 2016 Wiley Periodicals, Inc. ..
  85. Asai D, Murata M, Toita R, Kawano T, Nakashima H, Kang J. Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2). Amino Acids. 2016;48:2875-2880 pubmed
    ..Compared to the original peptide, a modified peptide (Ac-EEMEFSEAEANMN-NH2) exhibited markedly higher affinity for GRK2, but very low affinity for GRK5, suggesting that it can be a sensitive and selective peptide for GRK2.
  86. Fredericks Z, Pitcher J, Lefkowitz R. Identification of the G protein-coupled receptor kinase phosphorylation sites in the human beta2-adrenergic receptor. J Biol Chem. 1996;271:13796-803 pubmed
    ..Here we report the identification of the sites of GRK2- and GRK5-mediated beta2AR phosphorylation...
  87. Premont R, Claing A, Vitale N, Freeman J, Pitcher J, Patton W, et al. beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Proc Natl Acad Sci U S A. 1998;95:14082-7 pubmed
    ..Moreover, they provide a mechanism for integration of receptor activation and endocytosis through regulation of ARF protein activation by GRK-mediated recruitment of the GIT1 ARF GAP to the plasma membrane. ..
  88. Blaukat A, Pizard A, Breit A, Wernstedt C, Alhenc Gelas F, Muller Esterl W, et al. Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function. J Biol Chem. 2001;276:40431-40 pubmed
    ..The differential usage of clustered phosphoacceptor sites points to distinct roles of multiple kinases in controlling G protein-coupled receptor function. ..
  89. Warabi K, Richardson M, Barry W, Yamaguchi K, Roush E, Nishimura K, et al. Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro. FEBS Lett. 2002;521:140-4 pubmed
    ..Seven GRKs, designated GRK1 through 7, have been characterized. GRK5 is negatively regulated by protein kinase C...
  90. Millman E, Rosenfeld J, Vaughan D, Nguyen J, Dai W, Alpizar Foster E, et al. Endosome sorting of beta 2-adrenoceptors is GRK5 independent. Br J Pharmacol. 2004;141:277-84 pubmed
    1. We have investigated the role of G protein-coupled receptor kinase 5 (GRK5) in the regulation of endosome sorting of human beta(2)-adrenoceptors. 2...
  91. Spinelli L, Trimarco V, Di Marino S, Marino M, Iaccarino G, Trimarco B. L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome. Eur J Heart Fail. 2010;12:13-6 pubmed publisher