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GRK5

  • Reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 69 Accesses

Synonyms

GPRK5; G Protein-Coupled Receptor Kinase 5

Historical Background

Originally cloned in 1993 from human heart cDNA, G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase and the fifth member of the GRK family to be discovered (Kunapuli and Benovic 1993). Proteins of the GRK family are categorized into subgroups that are based upon kinase homology, amino acid sequence similarity, and tissue expression patterns. These subgroups are: the rhodopsin kinase subfamily (GRK1 and GRK7), the β-adrenergic receptor kinase (β-ARK) subfamily (GRK2 and GRK3), and the GRK4-like subfamily (GRK4, GRK5, and GRK6) (Nagayama et al. 1996; Xu et al. 2014).

Structure, Function, and Regulation

In humans, the Grk5 gene is located on chromosome 10q26.11 (Aken et al. 2016). The gene contains 16 exons and encodes a 590 amino acid–long protein with a molecular weight of ~67.7 kDa (Kunapuli and Benovic 1993). GRK5 exhibits high homology to the DrosophilaGPRK-2 and human IT11 proteins...

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References

  • Aken BL, Ayling S, Barrell D, Clarke L, Curwen V, Fairley S, et al. The Ensembl gene annotation system. Database (Oxford). 2016. https://doi.org/10.1093/database/baw093.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Carman CV, Som T, Kim CM, Benovic JL. Binding and phosphorylation of tubulin by G protein-coupled receptor kinases. J Biol Chem. 1998;273(32):20308–16.

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty PK, Zhang Y, Coomes AS, Kim WJ, Stupay R, Lynch LD, et al. G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer. Cancer Res. 2014;74(13):3489–500.

    Article  PubMed  CAS  Google Scholar 

  • Chen M, Philipp M, Wang J, Premont RT, Garrison TR, Caron MG, et al. G protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway. J Biol Chem. 2009;284(50):35040–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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(17):12823–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen Y, Wang F, Long H, Chen Y, Wu Z, Ma L. GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis. J Cell Biol. 2011;194(6):905–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng S, Li L, He S, Liu J, Sun Y, He M, et al. GRK5 deficiency accelerates ß-amyloid accumulation in Tg2576 mice via impaired cholinergic activity. J Biol Chem. 2010;285(53):41541–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chuang TT, Paolucci L, De Blasi A. Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin. J Biol Chem. 1996;271(45):28691–6.

    Article  PubMed  CAS  Google Scholar 

  • Dzimiri N, Muiya P, Andres E, Al-Halees Z. Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases. Eur J Pharmacol. 2004;489(3):167–77.

    Article  PubMed  CAS  Google Scholar 

  • Fan J, Malik AB. Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors. Nat Med. 2003;9(3):315–21.

    Article  PubMed  CAS  Google Scholar 

  • Freeman JLR, De La Cruz EM, Pollard TD, Lefkowitz RJ, Pitcher JA. Regulation of G protein-coupled receptor kinase 5 (GRK5) by actin. J Biol Chem. 1998;273(32):20653–7.

    Article  PubMed  CAS  Google Scholar 

  • Glück L, Loktev A, Moulédous L, Mollereau C, Law PY, Schulz S. Loss of morphine reward and dependence in mice lacking G protein-coupled receptor kinase 5. Biol Psychiatry. 2014;76(10):767–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gold JI, Martini JS, Hullmann J, Gao E, Chuprun JK, Lee L, et al. Nuclear translocation of cardiac G protein-coupled receptor kinase 5 downstream of select Gq-activating hypertrophic ligands is a calmodulin-dependent process. PLoS One. 2013;8(3):e57324.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gupta H, Jain A, Saadi AV, Vasudevan TG, Hande MH, D'Souza SC, et al. Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes. Infect Genet Evol. 2015;34:188–99.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hullmann JE, Grisanti LA, Makarewich CA, Gao E, Gold JI, Chuprun JK, et al. GRK5-mediated exacerbation of pathological cardiac hypertrophy involves facilitation of nuclear NFAT activity. Circ Res. 2014;115(12):976–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ishizaka N, Alexander RW, Laursen JB, Kai H, Fukui T, Oppermann M, et al. G protein-coupled receptor kinase 5 in cultured vascular smooth muscle cells and rat aorta: Regulation by angiotensin II and hypertension. J Biol Chem. 1997;272(51):32482–8.

    Article  PubMed  CAS  Google Scholar 

  • Islam KN, Bae JW, Gao E, Koch WJ. Regulation of nuclear factor κB (NF-κB) in the nucleus of cardiomyocytes by G protein-coupled receptor kinase 5 (GRK5). J Biol Chem. 2013;288(50):35683–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johnson LR, Scott MGH, Pitcher JA. G protein-coupled receptor kinase 5 contains a DNA-binding nuclear localization sequence. Mol Cell Biol. 2004;24(23):10169–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johnson LR, Robinson JD, Lester KN, Pitcher JA. Distinct structural features of G protein-coupled receptor kinase 5 (GRK5) regulate its nuclear localization and DNA-binding ability. PLoS One. 2013;8(5):e62508.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaur G, Kim J, Kaur R, Tan I, Bloch O, Sun MZ, et al. G-protein coupled receptor kinase (GRK)-5 regulates proliferation of glioblastoma-derived stem cells. J Clin Neurosci. 2013;20(7):1014–8.

    Article  PubMed  CAS  Google Scholar 

  • Kim JI, Chakraborty P, Wang Z, Daaka Y. G-protein coupled receptor kinase 5 regulates prostate tumor growth. J Urol. 2012;187(1):322–9.

    PubMed  CAS  Google Scholar 

  • Kunapuli P, Benovic JL. Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. Proc Natl Acad Sci U S A. 1993;90(12):5588–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kunapuli P, Gurevich VV, Benovic JL. Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5. J Biol Chem. 1994;269(14):10209–12.

    PubMed  CAS  Google Scholar 

  • Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, et al. A GRK5 polymorphism that inhibits ß-adrenergic receptor signaling is protective in heart failure. Nat Med. 2008;14(5):510–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu J, Rasul I, Sun Y, Wu G, Li L, Premont RT, et al. GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2/M4 autoreceptor desensitization. J Biol Chem. 2009;284(29):19564–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martini JS, Raake P, Vinge LE, DeGeorge Jr B, Chuprun JK, Harris DM, et al. Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc Natl Acad Sci U S A. 2008;105(34):12457–62.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nagayama Y, Tanaka K, Hara T, Namba H, Yamashita S, Taniyama K, et al. Involvement of G protein-coupled receptor kinase 5 in homologous desensitization of the thyrotropin receptor. J Biol Chem. 1996;271(17):10143–8.

    Article  PubMed  CAS  Google Scholar 

  • Packiriswamy N, Lee T, Raghavendra PB, Durairaj H, Wang H, Parameswaran N. G-protein-coupled receptor kinase-5 mediates inflammation but does not regulate cellular infiltration or bacterial load in a polymicrobial sepsis model in mice. J Innate Immun. 2013;5(4):401–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Packiriswamy N, Steury M, McCabe IC, Fitzgerald SD, Parameswaran N. Bacterial dose-dependent role of G protein-coupled receptor kinase 5 in Escherichia coli-induced pneumonia. Infect Immun. 2016;84(5):1633–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Patial S, Shahi S, Saini Y, Lee T, Packiriswamy N, Appledorn DM, et al. G-protein coupled receptor kinase 5 mediates lipopolysaccharide-induced NFκB activation in primary macrophages and modulates inflammation in vivo in mice. J Cell Physiol. 2011;226(5):1323–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pitcher JA, Fredericks ZL, Carl Stone W, Premont RT, Stoffel RH, Koch WJ, et al. Phosphatidylinositol 4,5-bisphosphate (PIP2)-enhanced G protein- coupled receptor kinase (GRK) activity. Location, structure, and regulation of the PIP2 binding site distinguishes the GRK families. J Biol Chem. 1996;271(40):24907–13.

    Article  PubMed  CAS  Google Scholar 

  • Premont RT, Koch WJ, Inglese J, Lefkowitz RJ. Identification, purification, and characterization of GRK5, a member of the family of G protein-coupled receptor kinases. J Biol Chem. 1994;269(9):6832–41.

    PubMed  CAS  Google Scholar 

  • Pronin AN, Benovic JL. Regulation of the G protein-coupled receptor kinase GRK5 by protein kinase C. J Biol Chem. 1997;272(6):3806–12.

    Article  PubMed  CAS  Google Scholar 

  • Pronin AN, Carman CV, Benovic JL. Structure-function analysis of G protein-coupled receptor kinase-5: Role of the carboxyl terminus in kinase regulation. J Biol Chem. 1998;273(47):31510–8.

    Article  PubMed  CAS  Google Scholar 

  • Purcell NH, Tang G, Yu C, Mercurio F, DiDonato JA, Lin A. Activation of NF-κB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc Natl Acad Sci U S A. 2001;98(12):6668–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rockman HA, Choi D-U, Rahman NU, Akhter SA, Lefkowitz RJ, Koch WJ. Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice. Proc Natl Acad Sci U S A. 1996;93(18):9954–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • So CH, Michal AM, Mashayekhi R, Benovic JL. G protein-coupled receptor kinase 5 phosphorylates nucleophosmin and regulates cell sensitivity to polo-like kinase 1 inhibition. J Biol Chem. 2012;287(21):17088–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sorriento D, Ciccarelli M, Santulli G, Campanile A, Altobelli GG, Cimini V, et al. The G-protein-coupled receptor kinase 5 inhibits NFκB transcriptional activity by inducing nuclear accumulation of IκBα. Proc Natl Acad Sci U S A. 2008;105(46):17818–23.

    Article  PubMed  PubMed Central  Google Scholar 

  • Suo Z, Wu M, Citron BA, Wong GT, Festoff BW. Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimer’s disease: an association with early ß-amyloid accumulation. J Neurosci. 2004;24(13):3444–52.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Suo Z, Cox AA, Bartelli N, Rasul I, Festoff BW, Premont RT, et al. GRK5 deficiency leads to early Alzheimer-like pathology and working memory impairment. Neurobiol Aging. 2007;28(12):1873–88.

    Article  PubMed  CAS  Google Scholar 

  • Xu H, Jiang X, Shen K, Fischer CC, Wedegaertner PB. The regulator of G protein signaling (RGS) domain of G protein-coupled receptor kinase 5 (GRK5) regulates plasma membrane localization and function. Mol Biol Cell. 2014;25(13):2105–15.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Chen L, Shen G, Zhao Q, Shangguan L, He M. GRK5 dysfunction accelerates tau hyperphosphorylation in APP (swe) mice through impaired cholinergic activity. Neuroreport. 2014;25(7):542–7.

    PubMed  Google Scholar 

  • Zhang Y, Shen GL, Shangguan LJ, Yu Y, He ML. Involvement of NFkappaB signaling in mediating the effects of GRK5 on neural stem cells. Brain Res. 2015;1608:31–9.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON, Canada

    Christopher Lowden & Hai-Ying Mary Cheng

  2. Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON, Canada

    Christopher Lowden & Hai-Ying Mary Cheng

Authors
  1. Christopher Lowden
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  2. Hai-Ying Mary Cheng
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Corresponding author

Correspondence to Christopher Lowden .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Lowden, C., Cheng, HY.M. (2018). GRK5. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101792

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