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G Protein-Coupled Receptor Kinases (GRKs) History: Evolution and Discovery

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G Protein-Coupled Receptor Kinases

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

The discovery of rhodopsin kinase (GRK1) was a major conceptual breakthrough in visual biochemistry that was later found to be relevant to the whole GPCR field. The existence of GRKs and arrestins revealed the primary mechanism for termination of GPCR signaling. GRKs appeared in evolution long before animals, and it remains to be elucidated whether their first substrates were GPCRs or other proteins. It is also unclear whether and how GRKs are activated to phosphorylate non-receptor substrates. All mammals have far fewer GRK subtypes than GPCRs. Despite this fact, GRKs are not totally promiscuous: impressive receptor-specific phenotypes of GRK knockouts along with lack of dramatic receptor preference in vitro suggest that receptor specificity in vivo is largely determined by differential expression in various cell types, as well as subcellular localization of particular GRKs to compartments where certain GPCRs reside. Biological role of GRKs is wider than just phosphorylation of GPCRs: these kinases modify a variety of non-receptor substrates and regulate cell signaling via mechanisms that do not depend on their enzymatic activity.

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References

  1. Bockaert J, Pin JP (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J 18:1723–1729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dessauer CW, Posner BA, Gilman AG (1996) Visualizing signal transduction: receptors, G-proteins, and adenylate cyclases. Clin Sci (Lond) 91(5):527–537

    Article  CAS  Google Scholar 

  3. Carman CV, Benovic JL (1998) G-protein-coupled receptors: turn-ons and turn-offs. Curr Opin Neurobiol 8:335–344

    Article  CAS  PubMed  Google Scholar 

  4. Gurevich EV, Gurevich VV (2006) Arrestins: ubiquitous regulators of cellular signaling pathways. Genome Biol 7(9):236

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Bownds D, Dawes J, Miller J, Stahlman M (1972) Phosphorylation of frog photoreceptor membranes induced by light. Nature 237:125–127

    CAS  Google Scholar 

  6. Kühn H, Dreyer WJ (1972) Light dependent phosphorylation of rhodopsin by ATP. FEBS Lett 20:1–6

    Article  PubMed  Google Scholar 

  7. Weller M, Virmaux N, Mandel P (1975) Light-stimulated phosphorylation of rhodopsin in the retina: the presence of a protein kinase that is specific for photobleached rhodopsin. Proc Natl Acad Sci U S A 72:381–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liebman PA, Pugh ENJ (1980) ATP mediates rapid reversal of cyclic GMP phosphodiesterase activation in visual receptor membranes. Nature 287:734–736

    Article  CAS  PubMed  Google Scholar 

  9. Kuhn H, Hall SW, Wilden U (1984) Light-induced binding of 48-kDa protein to photoreceptor membranes is highly enhanced by phosphorylation of rhodopsin. FEBS Lett 176:473–478

    Article  CAS  PubMed  Google Scholar 

  10. Wilden U, Hall SW, Kühn H (1986) Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments. Proc Natl Acad Sci U S A 83:1174–1178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dixon RA, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD (1986) Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 321:75–79

    Article  CAS  PubMed  Google Scholar 

  12. Benovic JL, DeBlasi A, Stone WC, Caron MG, Lefkowitz RJ (1989) Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science 246:235–240

    Article  CAS  PubMed  Google Scholar 

  13. Benovic JL, Mayor FJ, Somers RL, Caron MG, Lefkowitz RJ (1986) Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase. Nature 321:869–872

    Article  CAS  PubMed  Google Scholar 

  14. Benovic JL, Strasser RH, Caron MG, Lefkowitz RJ (1986) Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci U S A 83:2797–2801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Palczewski K (1997) GTP-binding-protein-coupled receptor kinases – two mechanistic models. Eur J Biochem 248:261–269

    Article  CAS  PubMed  Google Scholar 

  16. Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG (1996) Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274:768–770

    Article  CAS  PubMed  Google Scholar 

  17. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 477:549–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MHE, Zhang C, Moeller A, West GM, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhuty S, Conrad S, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JCH, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE (2015) Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser. Nature 523:561–567.

    Google Scholar 

  19. Carman CV, Som T, Kim CM, Benovic JL (1998) Binding and phosphorylation of tubulin by G protein-coupled receptor kinases. J Biol Chem 273:20308–20316

    Article  CAS  PubMed  Google Scholar 

  20. Pitcher JA, Hall RA, Daaka Y, Zhang J, Ferguson SS, Hester S, Miller S, Caron MG, Lefkowitz RJ, Barak LS (1998) The G protein-coupled receptor kinase 2 is a microtubule-associated protein kinase that phosphorylates tubulin. J Biol Chem 273:12316–12324

    Article  CAS  PubMed  Google Scholar 

  21. Haga K, Ogawa H, Haga T, Murofushi H (1998) GTP-binding-protein-coupled receptor kinase 2 (GRK2) binds and phosphorylates tubulin. Eur J Biochem 255:363–368

    Article  CAS  PubMed  Google Scholar 

  22. Pronin AN, Morris AJ, Surguchov A, Benovic JL (2000) Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem 275:26515–26522

    Article  CAS  PubMed  Google Scholar 

  23. Sakamoto M, Arawaka S, Hara S, Sato H, Cui C, Machiya Y, Koyama S, Wada M, Kawanami T, Kurita K, Kato T (2009) Contribution of endogenous G-protein-coupled receptor kinases to Ser129 phosphorylation of alpha-synuclein in HEK293 cells. Biochem Biophys Res Commun 384:378–382

    Article  CAS  PubMed  Google Scholar 

  24. Gurevich EV, Tesmer JJ, Mushegian A, Gurevich VV (2012) G protein-coupled receptor kinases: more than just kinases and not only for GPCRs. Pharmacol Ther 133:40–69

    Article  CAS  PubMed  Google Scholar 

  25. Palczewski K, Buczylko J, Kaplan MW, Polans AS, Crabb JW (1991) Mechanism of rhodopsin kinase activation. J Biol Chem 266:12949–12955

    CAS  PubMed  Google Scholar 

  26. Chen CY, Dion SB, Kim CM, Benovic JL (1993) Beta-adrenergic receptor kinase. Agonist-dependent receptor binding promotes kinase activation. J Biol Chem 268:7825–7831

    CAS  PubMed  Google Scholar 

  27. Freedman NJ, Kim LK, Murray JP, Exum ST, Brian L, Wu L-H, Peppel K (2002) Phosphorylation of the platelet-derived growth factor receptor-β and epidermal growth factor receptor by G protein-coupled receptor kinase-2: mechanisms for selectivity of desensitization. J Biol Chem 277:48261–48269

    Article  CAS  PubMed  Google Scholar 

  28. Wu J-H, Goswami R, Cai X, Exum ST, Huang X, Zhang L, Brian L, Premont RT, Peppel K, Freedman NJ (2006) Regulation of the platelet-derived growth factor receptor-β by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2*. J Biol Chem 281:37758–37772

    Article  CAS  PubMed  Google Scholar 

  29. Hildreth KL, Wu L-H, Barak LS, Exum ST, Kim LK, Peppel K, Freedman NJ (2004) Phosphorylation of the platelet-derived growth factor receptor-β by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na+/H+ exchanger regulatory factor. J Biol Chem 279:41775–41782

    Article  CAS  PubMed  Google Scholar 

  30. Wu J-H, Goswami R, Kim LK, Miller WE, Peppel K, Freedman NJ (2005) The platelet-derived growth factor receptor-β phosphorylates and activates G protein-coupled receptor kinase-2: a mechanisms for feedback inhibition. J Biol Chem 280:31027–31035

    Article  CAS  PubMed  Google Scholar 

  31. Johnson LR, Scott MG, Pitcher JA (2004) G protein-coupled receptor kinase 5 contains a DNA-binding nuclear localization sequence. Mol Cell Biol 24:10169–10179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Martini JS, Raake P, Vinge LE, DeGeorge BRJ, Chuprun JK, Harris DM, Gao E, Eckhart AD, Pitcher JA, Koch WJ (2008) Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc Natl Acad Sci U S A 105:12457–12462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ho J, Cocolakis E, Dumas VM, Posner BI, Laporte SA, Lebrun J-J (2005) The G protein-coupled receptor kinase-2 is a TGFβ-inducible antagonist of TGFβ signal transduction. EMBO J 24:3247–3258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Siderovski DP, Hessel A, Chung S, Mak TW, Tyers M (1996) A new family of regulators of G-protein-coupled receptors? Curr Biol 6:211–212

    Article  CAS  PubMed  Google Scholar 

  35. Carman CV, Parent JL, Day PW, Pronin AN, Sternweis PM, Wedegaertner PB, Gilman AG, Benovic JL, Kozasa T (1999) Selective regulation of Galpha(q/11) by an RGS domain in the G protein-coupled receptor kinase, GRK2. J Biol Chem 274:34483–34492

    Article  CAS  PubMed  Google Scholar 

  36. Usui H, Nishiyama M, Moroi K, Shibasaki T, Zhou J, Ishida J, Fukamizu A, Haga T, Sekiya S, Kimura S (2000) RGS domain in the amino-terminus of G protein-coupled receptor kinase 2 inhibits Gq-mediated signaling. Int J Mol Med 5(4):335–340

    CAS  PubMed  Google Scholar 

  37. Tesmer VM, Kawano T, Shankaranarayanan A, Kozasa T, Tesmer JJ (2005) Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex. Science 310:1686–1690

    Article  CAS  PubMed  Google Scholar 

  38. Day PW, Carman CV, Sterne-Marr R, Benovic JL, Wedegaertner PB (2003) Differential interaction of GRK2 with members of the G alpha q family. Biochemistry 42:9176–9184

    Article  CAS  PubMed  Google Scholar 

  39. Sterne-Marr R, Tesmer JJ, Day PW, Stracquatanio RP, Cilente JA, O’Connor KE, Pronin AN, Benovic JL, Wedegaertner PB (2003) G protein-coupled receptor Kinase 2/G alpha q/11 interaction. A novel surface on a regulator of G protein signaling homology domain for binding G alpha subunits. J Biol Chem 278:6050–6058

    Article  CAS  PubMed  Google Scholar 

  40. Luo J, Busillo JM, Benovic JL (2008) M3 muscarinic acetylcholine receptor-mediated signaling is regulated by distinct mechanisms. Mol Pharmacol 74:338–347

    Article  CAS  PubMed  Google Scholar 

  41. Willets JM, Nash MS, Challiss RA, Nahorski SR (2004) Imaging of muscarinic acetylcholine receptor signaling in hippocampal neurons: evidence for phosphorylation-dependent and -independent regulation by G-protein-coupled receptor kinases. J Neurosci 24:4157–4162

    Article  CAS  PubMed  Google Scholar 

  42. Ahmed MR, Bychkov E, Li L, Gurevich VV, Gurevich EV (2015) GRK3 suppresses l-DOPA-induced dyskinesia in the rat model of Parkinson’s disease via its RGS homology domain. Sci Rep 5:10920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Koch WJ, Inglese J, Stone WC, Lefkowitz RJ (1993) The binding site for the beta gamma subunits of heterotrimeric G proteins on the beta-adrenergic receptor kinase. J Biol Chem 268:8256–8260

    CAS  PubMed  Google Scholar 

  44. Touhara K, Inglese J, Pitcher JA, Shaw G, Lefkowitz RJ (1994) Binding of G protein beta gamma-subunits to pleckstrin homology domains. J Biol Chem 269:10217–10220

    CAS  PubMed  Google Scholar 

  45. Lodowski DT, Pitcher JA, Capel WD, Lefkowitz RJ, Tesmer JJ (2003) Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma. Science 300:1256–1262

    Article  CAS  PubMed  Google Scholar 

  46. Haga K, Haga T (1992) Activation by G protein beta gamma subunits of agonist- or light-dependent phosphorylation of muscarinic acetylcholine receptors and rhodopsin. J Biol Chem 267:2222–2227

    CAS  PubMed  Google Scholar 

  47. Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ (1992) Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. Science 257:1264–1267

    Article  CAS  PubMed  Google Scholar 

  48. Li J, Xiang B, Su W, Zhang X, Huang Y, Ma L (2003) Agonist-induced formation of opioid receptor-G protein-coupled receptor kinase (GRK)-G beta gamma complex on membrane is required for GRK2 function in vivo. J Biol Chem 278:30219–30226

    Article  CAS  PubMed  Google Scholar 

  49. Raveh A, Cooper A, Guy-David L, Reuveny E (2010) Nonenzymatic rapid control of GIRK channel function by a G protein-coupled receptor kinase. Cell 143:750–760

    Article  CAS  PubMed  Google Scholar 

  50. Premont RT, Claing A, Vitale N, Freeman JLR, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ (1998) β2-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 95:14082–14087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hoefen RJ, Berk BC (2006) The multifunctional GIT family of proteins. J Cell Sci 119:1469–1475

    Article  CAS  PubMed  Google Scholar 

  52. Penela P, Ribas C, Aymerich I, Eijkelkamp N, Barreiro O, Heijnen CJ, Kavelaars A, Sánchez-Madrid F, Mayor FJ (2008) G protein-coupled receptor kinase 2 positively regulates epithelial cell migration. EMBO J 27:1206–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Cleghorn WM, Branch KM, Kook S, Arnette C, Bulus N, Zent R, Kaverina I, Gurevich EV, Weaver AM, Gurevich VV (2015) Arrestins regulate cell spreading and motility via focal adhesion dynamics. Mol Biol Cell 26(4):622–635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gurevich VV, Hanson SM, Song X, Vishnivetskiy SA, Gurevich EV (2011) The functional cycle of visual arrestins in photoreceptor cells. Prog Retin Eye Res 30:405–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Premont RT, Macrae AD, Aparicio SA, Kendall HE, Welch JE, Lefkowitz RJ (1999) The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation. J Biol Chem 274(41):29381–29389

    Article  CAS  PubMed  Google Scholar 

  56. Mushegian A, Gurevich VV, Gurevich EV (2012) The origin and evolution of G protein-coupled receptor kinases. PLoS One 7(3):e33806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincus D, Putnam N, Rokas A, Wright KJ, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons JB, Morris A, Nichols S, Richter DJ, Salamov A, Sequencing JG, Bork P, Lim WA, Manning G, Miller WT, McGinnis W, Shapiro H, Tjian R, Grigoriev IV, Rokhsar D (2008) The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451:783–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ruiz-Trillo I, Lane CE, Archibald JM, Roger AJ (2006) Insights into the evolutionary origin and genome architecture of the unicellular opisthokonts Capsaspora owczarzaki and Sphaeroforma arctica. J Eukaryot Microbiol 53(5):379–384

    Article  CAS  PubMed  Google Scholar 

  59. Fukuto HS, Ferkey DM, Apicella AJ, Lans H, Sharmeen T, Chen W, Lefkowitz RJ, Jansen G, Schafer WR, Hart AC (2004) G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Neuron 42:581–593

    Article  CAS  PubMed  Google Scholar 

  60. Cassill JA, Whitney M, Joazeiro CAP, Becker A, Zuker CS (1991) Isolation of Drosophila genes encoding G protein-coupled receptor kinases. Proc Natl Acad Sci U S A 88:11067–11070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kikkawa S, Yoshida N, Nakagawa M, Iwasa T, Tsuda M (1998) A novel rhodopsin kinase in octopus photoreceptor possesses a pleckstrin homology domain and is activated by G protein betagamma-subunits. J Biol Chem 273:7441–7447

    Article  CAS  PubMed  Google Scholar 

  62. Li L, Homan KT, Vishnivetskiy SA, Manglik A, Tesmer JJ, Gurevich VV, Gurevich EV (2015) G protein-coupled receptor kinases of the GRK4 protein subfamily phosphorylate inactive G Protein-coupled Receptors (GPCRs). J Biol Chem 290(17):10775–10790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, Jenkins NA, Gilbert DJ, Copeland NG, Caron MG, Lefkowitz RJ (1991) Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. J Biol Chem 266:14939–14946

    CAS  PubMed  Google Scholar 

  64. Kunapuli P, Benovic JL (1993) Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. Proc Natl Acad Sci U S A 90:5588–5592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Holland PWH, Garcia-Fernandez J, Williams NA, Sidow A (1994) Gene duplications and the origins of vertebrate development. Development 120:125–133

    Google Scholar 

  66. Furlong RF, Holland PW (2004) Polyploidy in vertebrate ancestry: Ohno and beyond. Biol J Linnean Soc 82:425–430

    Article  Google Scholar 

  67. Donoghue PCJ, Purnell MA (2005) Genome duplication, extinction and vertebrate evolution. Trends Ecol Evol 20:312–319

    Article  PubMed  Google Scholar 

  68. Venkatesh B, Kirkness EF, Loh Y-H, Halpern AL, Lee AP, Johnson J, Dandona N, Viswanathan LD, Tay A, Venter JC, Strausberg RL, Brenner S (2007) Survey sequencing and comparative analysis of the elephant shark (Callorhinchus milii) genome. PLoS Biol 5(4):e101

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang N, Campbell MS, Yandell MD, Manousaki T, Meyer A, Bloom OE, Morgan JR, Buxbaum JD, Sachidanandam R, Sims C, Garruss AS, Cook M, Krumlauf R, Wiedemann LM, Sower SA, Decatur WA, Hall JA, Amemiya CT, Saha NR, Buckley KM, Rast JP, Das S, Hirano M, McCurley N, Guo P, Rohner N, Tabin CJ, Piccinelli P, Elgar G, Ruffier M, Aken BL, Searle SMJ, Muffato M, Pignatelli M, Herrero J, Jones M, Brown CT, Chung-Davidson Y-W, Nanlohy KG, Libants SV, Yeh C-Y, McCauley DW, Langeland JA, Pancer Z, Fritzsch B, de Jong PJ, Zhu B, Fulton LL, Theising B, Flicek P, Bronner ME, Warren WC, Clifton SW, Wilson RK, Li W (2013) Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat Genet 45(4):415–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Pao CS, Barker BL, Benovic JL (2009) Role of the amino terminus of G protein-coupled receptor kinase 2 in receptor phosphorylation. Biochemistry 48:7325–7333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Huang CC, Orban T, Jastrzebska B, Palczewski K, Tesmer JJ (2011) Activation of G protein-coupled receptor kinase 1 involves interactions between its N-terminal region and its kinase domain. Biochemistry 50(11):1940–1949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Boguth CA, Singh P, Huang CC, Tesmer JJ (2010) Molecular basis for activation of G protein-coupled receptor kinases. EMBO J 29:3249–3259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lodowski DT, Tesmer VM, Benovic JL, Tesmer JJ (2006) The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs. J Biol Chem 281:16785–16793

    Article  CAS  PubMed  Google Scholar 

  74. Inglese J, Glickman JF, Lorenz W, Caron MG, Lefkowitz RJ (1992) Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase. J Biol Chem 267(3):1422–1425

    CAS  PubMed  Google Scholar 

  75. Hisatomi O, Matsuda S, Satoh T, Kotaka S, Imanishi Y, Tokunaga F (1998) A novel subtype of G-protein-coupled receptor kinase, GRK7, in teleost cone photoreceptors. FEBS Lett 424:159–164

    Article  CAS  PubMed  Google Scholar 

  76. Jiang X, Benovic JL, Wedegaertner PB (2007) Plasma membrane and nuclear localization of G protein coupled receptor kinase 6A. Mol Biol Cell 18:2960–2969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Thiyagarajan MM, Stracquatanio RP, Pronin AN, Evanko DS, Benovic JL, Wedegaertner PB (2004) A predicted amphipathic helix mediates plasma membrane localization of GRK5. J Biol Chem 279:17989–17995

    Article  CAS  PubMed  Google Scholar 

  78. Premont RT, Macrae AD, Stoffel RH, Chung N, Pitcher JA, Ambrose C, Inglese J, MacDonald ME, Lefkowitz RJ (1996) Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants. J Biol Chem 271:6403–6410

    Article  CAS  PubMed  Google Scholar 

  79. Manning G, Plowman GD, Hunter T, Sudarsanam S (2002) Evolution of protein kinase signaling from yeast to man. Trends Biochem Sci 27:514–520

    Article  CAS  PubMed  Google Scholar 

  80. Wilkie TM, Kinch L (2005) New roles for Galpha and RGS proteins: communication continues despite pulling sisters apart. Curr Biol 15:R843–R854

    Article  CAS  PubMed  Google Scholar 

  81. Kimple AJ, Bosch DE, Giguère PM, Siderovski DP (2011) Regulators of G-protein signaling and their Gα substrates: promises and challenges in their use as drug discovery targets. Pharmacol Rev 63(3):728–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Rompler H, Staubert C, Thor D, Schulz A, Hofreiter M, Schoneberg T (2007) G protein-coupled time travel: evolutionary aspects of GPCR research. Mol Interv 7:17–25

    Article  PubMed  Google Scholar 

  83. Fredriksson R, Schiöth HB (2005) The repertoire of G-protein-coupled receptors in fully sequenced genomes. Mol Pharmacol 67:1414–1425

    Article  CAS  PubMed  Google Scholar 

  84. de Mendoza A, Sebé-Pedrós A, Ruiz-Trillo I (2014) The evolution of the GPCR signaling system in eukaryotes: modularity, conservation, and the transition to metazoan multicellularity. Genome Biol Evol 6(3):606–619

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Strotmann R, Schröck K, Böselt I, Stäubert C, Russ A, Schöneberg T (2011) Evolution of GPCR: change and continuity. Mol Cell Endocrinol 331(2):170–178

    Article  CAS  PubMed  Google Scholar 

  86. Krishnan A, Almén MS, Fredriksson R, Schiöth HB (2012) The origin of GPCRs: identification of mammalian like rhodopsin, adhesion, glutamate and frizzled GPCRs in fungi. PLoS One 7(e29817)

    Google Scholar 

  87. Mackin KA, Roy RA, Theobald DL (2014) An empirical test of convergent evolution in rhodopsins. Mol Biol Evol 31(1):85–95

    Article  CAS  PubMed  Google Scholar 

  88. Shalaeva DN, Galperin MY, Mulkidjanian AY (2015) Eukaryotic G protein-coupled receptors as descendants of prokaryotic sodium-translocating rhodopsins. Biol Direct 10:63

    Article  PubMed  PubMed Central  Google Scholar 

  89. Anantharaman V, Abhiman S, de Souza RF, Aravind L (2011) Comparative genomics uncovers novel structural and functional features of the heterotrimeric GTPase signaling system. Gene 475(2):63–78

    Article  CAS  PubMed  Google Scholar 

  90. Alvarez CE (2008) On the origins of arrestin and rhodopsin. BMC Evol Biol 8:222–222

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Shi H, Rojas R, Bonifacino JS, Hurley JH (2006) The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain. Nat Struct Mol Biol 13(6):540–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Boase NA, Kelly JM (2004) A role for creD, a carbon catabolite repression gene from Aspergillus nidulans, in ubiquitination. Mol Microbiol 53(3):929–940

    Article  CAS  PubMed  Google Scholar 

  93. Herranz S, Rodríguez JM, Bussink H-J, Sánchez-Ferrero JC, Arst HN, Peñalva MA, Vincent O (2005) Arrestin-related proteins mediate pH signaling in fungi. Proc Natl Acad Sci U S A 102(34):12141–12146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Nordström KJ, Sällman Almén M, Edstam MM, Fredriksson R, Schiöth HB (2011) Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families. Mol Biol Evol 28:2471–2480

    Article  PubMed  CAS  Google Scholar 

  95. Homan KT, Tesmer JJ (2014) Structural insights into G protein-coupled receptor kinase function. Curr Opin Cell Biol 27:25–31

    Article  CAS  PubMed  Google Scholar 

  96. Huang CC, Tesmer JJ (2011) Recognition in the face of diversity: interactions of heterotrimeric G proteins and G protein-coupled receptor (GPCR) kinases with activated GPCRs. J Biol Chem 286:7715–7721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Feuerstein SE, Pulvermüller A, Hartmann R, Granzin J, Stoldt M, Henklein P, Ernst OP, Heck M, Willbold D, Koenig BW (2009) Helix formation in arrestin accompanies recognition of photoactivated rhodopsin. Biochemistry 48(45):10733–10742

    Article  CAS  PubMed  Google Scholar 

  98. Szczepek M, Beyriere F, Hofmann KP, Elgeti M, Kazmin R, Rose A, Bartl FJ, von Stetten D, Heck M, Sommer ME, Hildebrand PW, Scheerer P (2014) Crystal structure of a common GPCR-binding interface for G protein and arrestin. Nat Commun 5:4801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Gurevich VV, Gurevich EV (2004) The molecular acrobatics of arrestin activation. Trends Pharmacol Sci 25:105–111

    Article  CAS  PubMed  Google Scholar 

  100. Gimenez LE, Kook S, Vishnivetskiy SA, Ahmed MR, Gurevich EV, Gurevich VV (2012) Role of receptor-attached phosphates in binding of visual and non-visual arrestins to G protein-coupled receptors. J Biol Chem 287(12):9028–9040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lohse MJ, Andexinger S, Pitcher J, Trukawinski S, Codina J, Faure JP, Caron MG, Lefkowitz RJ (1992) Receptor-specific desensitization with purified proteins. Kinase dependence and receptor specificity of beta-arrestin and arrestin in the beta 2-adrenergic receptor and rhodopsin systems. J Biol Chem 267:8558–8564

    CAS  PubMed  Google Scholar 

  102. Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (1990) beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 248:1547–1550

    Article  CAS  PubMed  Google Scholar 

  103. Hirsch JA, Schubert C, Gurevich VV, Sigler PB (1999) The 2.8 A crystal structure of visual arrestin: a model for arrestin’s regulation. Cell 97(2):257–269

    Article  CAS  PubMed  Google Scholar 

  104. Han M, Gurevich VV, Vishnivetskiy SA, Sigler PB, Schubert C (2001) Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane translocation. Structure 9(9):869–880

    Article  CAS  PubMed  Google Scholar 

  105. Sutton RB, Vishnivetskiy SA, Robert J, Hanson SM, Raman D, Knox BE, Kono M, Navarro J, Gurevich VV (2005) Crystal structure of cone arrestin at 2.3Å: evolution of receptor specificity. J Mol Biol 354:1069–1080

    Article  CAS  PubMed  Google Scholar 

  106. Zhan X, Gimenez LE, Gurevich VV, Spiller BW (2011) Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual arrestins. J Mol Biol 406:467–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kim M, Vishnivetskiy SA, Van Eps N, Alexander NS, Cleghorn WM, Zhan X, Hanson SM, Morizumi T, Ernst OP, Meiler J, Gurevich VV, Hubbell WL (2012) Conformation of receptor-bound visual arrestin. Proc Natl Acad Sci U S A 109(45):18407–18412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Chen Q, Gilbert NC, Perry NA, Zhuo Y, Vishnivetskiy SA, Berndt S, Klug CS, Gurevich VV, Iverson TM (2016) Structural basis for arrestin-3 activation by inositol hexakisphosphate. Cell, In revision

    Google Scholar 

  109. Vishnivetskiy SA, Paz CL, Schubert C, Hirsch JA, Sigler PB, Gurevich VV (1999) How does arrestin respond to the phosphorylated state of rhodopsin? J Biol Chem 274:11451–11454

    Article  CAS  PubMed  Google Scholar 

  110. Binder BM, Biernbaum MS, Bownds MD (1990) Light activation of one rhodopsin molecule causes the phosphorylation of hundreds of others. A reaction observed in electropermeabilized frog rod outer segments exposed to dim illumination. J Biol Chem 265:15333–15340

    CAS  PubMed  Google Scholar 

  111. Binder BM, O’Connor TM, Bownds MD, Arshavsky VY (1996) Phosphorylation of non-bleached rhodopsin in intact retinas and living frogs. J Biol Chem 271:19826–19830

    Article  CAS  PubMed  Google Scholar 

  112. Gurevich VV, Gurevich EV (2008) GPCR monomers and oligomers: it takes all kinds. Trends Neurosci 31:74–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Gurevich VV, Gurevich EV (2008) How and why do GPCRs dimerize? Trends Pharmacol Sci 29:234–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Pearce LR, Komander D, Alessi DR (2010) The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol 11(1):9–22

    Article  CAS  PubMed  Google Scholar 

  115. Tesmer JJ, Tesmer VM, Lodowski DT, Steinhagen H, Huber J (2010) Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol. J Med Chem 53(4):1867–1870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Singh P, Wang B, Maeda T, Palczewski K, Tesmer JJ (2008) Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation. J Biol Chem 283(20):14053–14062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Homan KT, Waldschmidt HV, Glukhova A, Cannavo A, Song J, Cheung JY, Koch WJ, Larsen SD, Tesmer JJ (2015) Crystal structure of G protein-coupled receptor kinase 5 in complex with a rationally designed inhibitor. J Biol Chem 290(34):20649–20659

    Article  CAS  PubMed  Google Scholar 

  118. Komolov KE, Bhardwaj A, Benovic JL (2015) Atomic structure of GRK5 reveals distinct structural features novel for G protein-coupled receptor kinases. J Biol Chem 290(34):20629–20647

    Article  CAS  PubMed  Google Scholar 

  119. Ménard L, Ferguson SS, Barak LS, Bertrand L, Premont RT, Colapietro AM, Lefkowitz RJ, Caron MG (1996) Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration. Biochemistry 35(13):4155–4160

    Article  PubMed  Google Scholar 

  120. Rankin ML, Marinec PS, Cabrera DM, Wang Z, Jose PA, Sibley DR (2006) The D1 dopamine receptor is constitutively phosphorylated by G protein-coupled receptor kinase 4. Mol Pharmacol 69(3):759–769

    CAS  PubMed  Google Scholar 

  121. Inagaki S, Ghirlando R, Vishnivetskiy SA, Homan KT, White JF, Tesmer JJ, Gurevich VV, Grisshammer R (2015) G protein-coupled receptor kinase 2 (GRK2) and 5 (GRK5) exhibit selective phosphorylation of the neurotensin receptor in vitro. Biochemistry 54(28):4320–4329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Loudon RP, Benovic JL (1997) Altered activity of palmitoylation-deficient and isoprenylated forms of the G protein-coupled receptor kinase GRK6. J Biol Chem 272(43):27422–27427

    Article  CAS  PubMed  Google Scholar 

  123. Stoffel RH, Randall RR, Premont RT, Lefkowitz RJ, Inglese J (1994) Palmitoylation of G protein-coupled receptor kinase, GRK6. Lipid modification diversity in the GRK family. J Biol Chem 269(45):27791–27794

    CAS  PubMed  Google Scholar 

  124. Pitcher JA, Fredericks ZL, Stone WC, Premont RT, Stoffel RH, Koch WJ, Lefkowitz RJ (1996) 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 subfamilies. J Biol Chem 271:24907–24913

    Article  CAS  PubMed  Google Scholar 

  125. Gurevich EV, Benovic JL, Gurevich VV (2004) Arrestin2 expression selectively increases during neural differentiation. J Neurochem 91(6):1404–1416

    Article  CAS  PubMed  Google Scholar 

  126. Ahmed MR, Bychkov E, Gurevich VV, Benovic JL, Gurevich EV (2007) Altered expression and subcellular distribution of GRK subtypes in the dopamine-depleted rat basal ganglia is not normalized by l-DOPA treatment. J Neurochem 104:1622–1636

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Bychkov E, Gurevich VV, Joyce JN, Benovic JL, Gurevich EV (2008) Arrestins and two receptor kinases are upregulated in Parkinson’s disease with dementia. Neurobiol Aging 29:379–396

    Article  CAS  PubMed  Google Scholar 

  128. Bychkov ER, Ahmed MR, Gurevich VV, Benovic JL, Gurevich EV (2011) Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis 44(2):248–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Ahmed MR, Berthet A, Bychkov E, Porras G, Li Q, Bioulac BH, Carl YT, Bloch B, Kook S, Aubert I, Dovero S, Doudnikoff E, Gurevich VV, Gurevich EV, Bezard E (2010) Lentiviral overexpression of GRK6 alleviates l-dopa-induced dyskinesia in experimental Parkinson’s disease. Sci Transl Med 2:28ra28

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Gainetdinov RR, Bohn LM, Sotnikova TD, Cyr M, Laakso A, Macrae AD, Torres GE, Kim KM, Lefkowitz RJ, Caron MG, Premont RT (2003) Dopaminergic supersensitivity in G protein-coupled receptor kinase 6-deficient mice. Neuron 38:291–303

    Article  CAS  PubMed  Google Scholar 

  131. Gainetdinov RR, Bohn LM, Walker JK, Laporte SA, Macrae AD, Caron MG, Lefkowitz RJ, Premont RT (1999) Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron 24(4):1029–1036

    Article  CAS  PubMed  Google Scholar 

  132. Kim CM, Dion SB, Benovic JL (1993) Mechanism of beta-adrenergic receptor kinase activation by G proteins. J Biol Chem 268:15412–15418

    CAS  PubMed  Google Scholar 

  133. Vishnivetskiy SA, Ostermaier MK, Singhal A, Panneels V, Homan KT, Glukhova A, Sligar SG, Tesmer JJ, Schertler GF, Standfuss J, Gurevich VV (2013) Constitutively active rhodopsin mutants causing night blindness are effectively phosphorylated by GRKs but differ in arrestin-1 binding. Cell Signal 25(11):2155–2162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Vanderbilt University, 2200 Pierce Avenue, Preston Research Building, Rm. 454, Nashville, TN, 37232, USA

    Vsevolod V. Gurevich & Eugenia V. Gurevich

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  1. Vsevolod V. Gurevich
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  2. Eugenia V. Gurevich
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Correspondence to Vsevolod V. Gurevich .

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  1. Department of Pharmacology, Vanderbilt University , NASHVILLE, Tennessee, USA

    Vsevolod V. Gurevich

  2. Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

    Eugenia V. Gurevich

  3. Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA

    John J.G. Tesmer

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Gurevich, V.V., Gurevich, E.V. (2016). G Protein-Coupled Receptor Kinases (GRKs) History: Evolution and Discovery. In: Gurevich, V., Gurevich, E., Tesmer, J. (eds) G Protein-Coupled Receptor Kinases. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3798-1_1

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