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Structure and Function of G-Protein-Coupled Receptor Kinases 1 and 7

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G Protein-Coupled Receptor Kinases

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

Abstract

The importance of G protein-coupled receptor (GPCR) kinases (GRKs) as regulators of GPCR signaling has been widely recognized. In humans, GRKs constitute a family of seven protein kinases involved in the phosphorylation and desensitization of agonist-activated GPCRs in many physiological processes. The GPCR desensitization process is initiated by GRKs, but involves several subsequent steps including arrestin capping of phosphorylated receptors. High-resolution crystal structures were determined for four members of the GRK family, i.e., GRK1, GRK2, GRK5, and GRK6. This allowed decoding of the molecular basis of GRK activation and interactions with GPCR substrates, as well as the GRK interactions with cellular membranes and inhibitors. Here, we focused on retinal GRKs, or photopigment kinases, rhodopsin kinase (GRK1), and GRK7, in the context of major general advances in the GRK field.

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Abbreviations

CaM:

Calmodulin

GPCRs:

G protein-coupled receptors

GRKs:

G protein-coupled receptor kinases

PDE:

Phosphodiesterase

PKA:

Protein kinase A

Rho:

Rhodopsin

Rho*:

Photoactivated rhodopsin

References

  1. Palczewski K, Benovic JL (1991) G-protein-coupled receptor kinases. Trends Biochem Sci 16(10):387–391

    Article  CAS  PubMed  Google Scholar 

  2. Benovic JL, Mayor F Jr, Somers RL, Caron MG, Lefkowitz RJ (1986) Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase. Nature 321(6073):869–872

    Article  CAS  PubMed  Google Scholar 

  3. Felder RA, Sanada H, Xu J, Yu PY, Wang Z, Watanabe H, Asico LD, Wang W, Zheng SP, Yamaguchi I, Williams SM, Gainer J, Brown NJ, Hazen-Martin D, Wong LJC, Robillard JE, Carey RM, Eisner GM, Jose PA (2002) G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl Acad Sci U S A 99(6):3872–3877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gold JI, Gao EH, Shang XY, Premont RT, Koch WJ (2012) Determining the absolute requirement of G protein-coupled receptor kinase 5 for pathological cardiac hypertrophy. Circ Res 111(8):1048–1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dryja TP (2000) Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture. Am J Ophthalmol 130(5):547–563

    Article  CAS  PubMed  Google Scholar 

  6. Lymperopoulos A, Rengo G, Koch WJ (2012) GRK2 inhibition in heart failure: something old, something new. Curr Pharm Design 18(2):186–191

    Article  CAS  Google Scholar 

  7. Gurevich EV, Premont RT, Gainetdinov RR (2015) G protein-coupled receptor kinases: from molecules to diseases. FASEB J 29(2):361–364

    Article  CAS  PubMed  Google Scholar 

  8. Purves D, Augustine GJ, Fitzpatrick D, Katz L, LaMantia A-S, McNamara J, Williams S (2001) The retina. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. The Retina. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10885/

  9. Euler T, Haverkamp S, Schubert T, Baden T (2014) Retinal bipolar cells: elementary building blocks of vision. Nat Rev Neurosci 15(8):507–519

    Article  CAS  PubMed  Google Scholar 

  10. Baylor DA, Lamb TD, Yau KW (1979) Responses of retinal rods to single photons. J Physiol 288(Mar):613–634

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Baylor DA (1987) Photoreceptor signals and vision. Invest Ophth Vis Sci 28(1):34–49

    CAS  Google Scholar 

  12. Fain GL, Matthews HR, Cornwall MC, Koutalos Y (2001) Adaptation in vertebrate photoreceptors. Physiol Rev 81(1):117–151

    CAS  PubMed  Google Scholar 

  13. Palczewski K (2006) G protein-coupled receptor rhodopsin. Annu Rev Biochem 75:743–767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kiser PD, Golczak M, Palczewski K (2014) Chemistry of the retinoid (visual) cycle. Chem Rev 114(1):194–232

    Article  CAS  PubMed  Google Scholar 

  15. Kiser PD, Zhang J, Badiee M, Li Q, Shi W, Sui X, Golczak M, Tochtrop GP, Palczewski K (2015) Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nat Chem Biol 11(6):409–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kiser PD, Golczak M, Maeda A, Palczewski K (2012) Key enzymes of the retinoid (visual) cycle in vertebrate retina. Biochim Biophys Acta 1821(1):137–151

    Article  CAS  PubMed  Google Scholar 

  17. Krupnick JG, Gurevich VV, Benovic JL (1997) Mechanism of quenching of phototransduction. Binding competition between arrestin and transducin for phosphorhodopsin. J Biol Chem 272(29):18125–18131

    Article  CAS  PubMed  Google Scholar 

  18. Hofmann KP, Pulvermuller A, Buczylko J, Van Hooser P, Palczewski K (1992) The role of arrestin and retinoids in the regeneration pathway of rhodopsin. J Biol Chem 267(22):15701–15706

    CAS  PubMed  Google Scholar 

  19. Wilden U, Kuhn H (1982) Light-dependent phosphorylation of rhodopsin: number of phosphorylation sites. Biochemistry 21(12):3014–3022

    Article  CAS  PubMed  Google Scholar 

  20. Kuhn H, Wilden U (1987) Deactivation of photoactivated rhodopsin by rhodopsin-kinase and arrestin. J Recept Res 7(1-4):283–298

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  22. Miller JA, Brodie AE, Bownds MD (1975) Light-activated rhodopsin phosphorylation may control light sensitivity in isolated rod outer segments. FEBS Lett 59(1):20–23

    Article  CAS  PubMed  Google Scholar 

  23. 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(1):381–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bownds D, Dawes J, Miller J, Stahlman M (1972) Phosphorylation of frog photoreceptor membranes induced by light. Nat New Biol 237(73):125–127

    Article  CAS  PubMed  Google Scholar 

  25. Hurley JB, Spencer M, Niemi GA (1998) Rhodopsin phosphorylation and its role in photoreceptor function. Vision Res 38(10):1341–1352

    Article  CAS  PubMed  Google Scholar 

  26. Baylor DA, Burns ME (1998) Control of rhodopsin activity in vision. Eye 12:521–525

    Article  PubMed  Google Scholar 

  27. Stryer L (1986) Cyclic GMP cascade of vision. Annu Rev Neurosci 9:87–119

    Article  CAS  PubMed  Google Scholar 

  28. Sitaramayya A, Liebman PA (1983) Phosphorylation of rhodopsin and quenching of cyclic GMP phosphodiesterase activation by ATP at weak bleaches. J Biol Chem 258(20):12106–12109

    CAS  PubMed  Google Scholar 

  29. Kennedy MJ, Lee KA, Niemi GA, Craven KB, Garwin GG, Saari JC, Hurley JB (2001) Multiple phosphorylation of rhodopsin and the in vivo chemistry underlying rod photoreceptor dark adaptation. Neuron 31(1):87–101

    Article  CAS  PubMed  Google Scholar 

  30. Ohguro H, Van Hooser JP, Milam AH, Palczewski K (1995) Rhodopsin phosphorylation and dephosphorylation in vivo. J Biol Chem 270(24):14259–14262

    Article  CAS  PubMed  Google Scholar 

  31. Ohguro H, RudnickaNawrot M, Buczylko J, Zhao XY, Taylor JA, Walsh KA, Palczewski K (1996) Structural and enzymatic aspects of rhodopsin phosphorylation. J Biol Chem 271(9):5215–5224

    Article  CAS  PubMed  Google Scholar 

  32. Mendez A, Burns ME, Roca A, Lem J, Wu LW, Simon MI, Baylor DA, Chen J (2000) Rapid and reproducible deactivation of rhodopsin requires multiple phosphorylation sites. Neuron 28(1):153–164

    Article  CAS  PubMed  Google Scholar 

  33. Azevedo AW, Doan T, Moaven H, Sokal I, Baameur F, Vishnivetskiy SA, Homan KT, Tesmer JJ, Gurevich VV, Chen J, Rieke F (2015) C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor. Elife 4:e05981

    Google Scholar 

  34. Fredericks ZL, Pitcher JA, Lefkowitz RJ (1996) Identification of the G protein-coupled receptor kinase phosphorylation sites in the human beta(2)-adrenergic receptor. J Biol Chem 271(23):13796–13803

    Article  CAS  PubMed  Google Scholar 

  35. Palczewski K, Hargrave PA, Mcdowell JH, Ingebritsen TS (1989) The catalytic subunit of phosphatase 2a dephosphorylates phosphoopsin. Biochemistry 28(2):415–419

    Article  CAS  PubMed  Google Scholar 

  36. Palczewski K, McDowell JH, Hargrave PA (1988) Purification and characterization of rhodopsin kinase. J Biol Chem 263(28):14067–14073

    CAS  PubMed  Google Scholar 

  37. Weiss ER, Raman D, Shirakawa S, Ducceschi MH, Bertram PT, Wong F, Kraft TW, Osawa S (1998) The cloning of GRK7, a candidate cone opsin kinase, from cone- and rod-dominant mammalian retinas. Mol Vis 4:27

    CAS  PubMed  Google Scholar 

  38. 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(3):159–164

    Article  CAS  PubMed  Google Scholar 

  39. Weiss ER, Ducceschi MH, Horner TJ, Li A, Craft CM, Osawa S (2001) Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction. J Neurosci 21(23):9175–9184

    CAS  PubMed  Google Scholar 

  40. Wada Y, Sugiyama J, Okano T, Fukada Y (2006) GRK1 and GRK7: unique cellular distribution and widely different activities of opsin phosphorylation in the zebrafish rods and cones. J Neurochem 98(3):824–837

    Article  CAS  PubMed  Google Scholar 

  41. Liu P, Osawa S, Weiss ER (2005) M opsin phosphorylation in intact mammalian retinas. J Neurochem 93(1):135–144

    Article  CAS  PubMed  Google Scholar 

  42. Osawa S, Weiss ER (2012) A tale of two kinases in rods and cones. Adv Exp Med Biol 723:821–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shimauchi-Matsukawa Y, Aman Y, Tachibanaki S, Kawamura S (2005) Isolation and characterization of visual pigment kinase-related genes in carp retina: polyphyly in GRK1 subtypes, GRK1A and 1B. Mol Vis 11:1220–1228

    CAS  PubMed  Google Scholar 

  44. Zhao XY, Huang J, Khani SC, Palczewski K (1998) Molecular forms of human rhodopsin kinase (GRK1). J Biol Chem 273(9):5124–5131

    Article  CAS  PubMed  Google Scholar 

  45. Tachibanaki S, Arinobu D, Shimauchi-Matsukawa Y, Tsushima S, Kawamura S (2005) Highly effective phosphorylation by G protein-coupled receptor kinase 7 of light-activated visual pigment in cones. Proc Natl Acad Sci U S A 102(26):9329–9334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rinner O, Makhankov YV, Biehlmaier O, Neuhauss SCF (2005) Knockdown of cone-specific kinase GRK7 in larval zebrafish leads to impaired cone response recovery and delayed dark adaptation. Neuron 47(2):231–242

    Article  CAS  PubMed  Google Scholar 

  47. Vogalis F, Shiraki T, Kojima D, Wada Y, Nishiwaki Y, Jarvinen JLP, Sugiyama J, Kawakami K, Masai I, Kawamura S, Fukada Y, Lamb TD (2011) Ectopic expression of cone-specific G-protein-coupled receptor kinase GRK7 in zebrafish rods leads to lower photosensitivity and altered responses. J Physiol 589(9):2321–2348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Khani SC, Abitbol M, Yamamoto S, MaravicMagovcevic I, Dryja TP (1996) Characterization and chromosomal localization of the gene for human rhodopsin kinase. Genomics 35(3):571–576

    Article  CAS  PubMed  Google Scholar 

  49. Maeda T, Imanishi Y, Palczewski K (2003) Rhodopsin phosphorylation: 30 years later. Prog Retin Eye Res 22(4):417–434

    Article  CAS  PubMed  Google Scholar 

  50. Yamamoto S, Sippel KC, Berson EL, Dryja TP (1997) Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness. Nat Genet 15(2):175–178

    Article  CAS  PubMed  Google Scholar 

  51. Khani SC, Nielsen L, Vogt TM (1998) Biochemical evidence for pathogenicity of rhodopsin kinase mutations correlated with the oguchi form of congenital stationary night blindness. Proc Natl Acad Sci U S A 95(6):2824–2827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fuchs S, Nakazawa M, Maw M, Tamai M, Oguchi Y, Gal A (1995) A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat Genet 10(3):360–362

    Article  CAS  PubMed  Google Scholar 

  53. Huang LL, Li W, Tang WL, Zhu XH, Ou-yang PB, Lu GX (2012) A Chinese family with Oguchi’s disease due to compound heterozygosity including a novel deletion in the arrestin gene. Mol Vis 18(57–59):528–536

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Waheed NK, Qavi AH, Malik SN, Maria M, Riaz M, Cremers FP, Azam M, Qamar R (2012) A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease. Mol Vis 18:1253–1259

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang Q, Zulfiqar F, Riazuddin SA, Xiao X, Yasmeen A, Rogan PK, Caruso R, Sieving PA, Riazuddin S, Hejtmancik JF (2005) A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. Mol Vis 11:977–985

    CAS  PubMed  Google Scholar 

  56. Cideciyan AV, Zhao X, Nielsen L, Khani SC, Jacobson SG, Palczewski K (1998) Null mutation in the rhodopsin kinase gene slows recovery kinetics of rod and cone phototransduction in man. Proc Natl Acad Sci U S A 95(1):328–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hayashi T, Gekka T, Takeuchi T, Goto-Omoto S, Kitahara K (2007) A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses. Ophthalmology 114(1):134–141

    Article  PubMed  Google Scholar 

  58. Oishi A, Akimoto M, Kawagoe N, Mandai M, Takahashi M, Yoshimura N (2007) Novel mutations in the GRK1 gene in Japanese patients with Oguchi disease. Am J Ophthalmol 144(3):475–477

    Article  CAS  PubMed  Google Scholar 

  59. Azam M, Collin RW, Khan MI, Shah ST, Qureshi N, Ajmal M, den Hollander AI, Qamar R, Cremers FP (2009) A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family. Mol Vis 15:1788–1793

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Chen CK, Burns ME, Spencer M, Niemi GA, Chen J, Hurley JB, Baylor DA, Simon MI (1999) Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase. Proc Natl Acad Sci U S A 96(7):3718–3722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lyubarsky AL, Chen C, Simon MI, Pugh EN Jr (2000) Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses. J Neurosci 20(6):2209–2217

    CAS  PubMed  Google Scholar 

  62. Fan J, Sakurai K, Chen CK, Rohrer B, Wu BX, Yau KW, Kefalov V, Crouch RK (2010) Deletion of GRK1 causes retina degeneration through a transducin-independent mechanism. J Neurosci 30(7):2496–2503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cideciyan AV, Jacobson SG, Gupta N, Osawa S, Locke KG, Weiss ER, Wright AF, Birch DG, Milam AH (2003) Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3. Invest Ophthalmol Vis Sci 44(3):1268–1274

    Article  PubMed  Google Scholar 

  64. Yetemian RM, Brown BM, Craft CM (2010) Neovascularization, enhanced inflammatory response, and age-related cone dystrophy in the Nrl−/−Grk1−/− mouse retina. Invest Ophthalmol Vis Sci 51(12):6196–6206

    Article  PubMed  PubMed Central  Google Scholar 

  65. Whitcomb T, Sakurai K, Brown BM, Young JE, Sheflin L, Dlugos C, Craft CM, Kefalov VJ, Khani SC (2010) Effect of g protein-coupled receptor kinase 1 (Grk1) overexpression on rod photoreceptor cell viability. Invest Ophthalmol Vis Sci 51(3):1728–1737

    Article  PubMed  PubMed Central  Google Scholar 

  66. Sakurai K, Young JE, Kefalov VJ, Khani SC (2011) Variation in rhodopsin kinase expression alters the dim flash response shut off and the light adaptation in rod photoreceptors. Invest Ophthalmol Vis Sci 52(9):6793–6800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Orban T, Jastrzebska B, Palczewski K (2014) Structural approaches to understanding retinal proteins needed for vision. Curr Opin Cell Biol 27:32–43

    Article  CAS  PubMed  Google Scholar 

  68. 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(5623):1256–1262

    Article  CAS  PubMed  Google Scholar 

  69. Komolov KE, Bhardwaj A, Benovic JL (2015) Atomic structure of G protein-coupled receptor kinase 5 (GRK5) reveals distinct structural features novel for GRKs. J Biol Chem 290(34):20629–20647

    Article  CAS  PubMed  Google Scholar 

  70. 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 

  71. 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 

  72. Boguth CA, Singh P, Huang CC, Tesmer JJ (2010) Molecular basis for activation of G protein-coupled receptor kinases. EMBO J 29(19):3249–3259

    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(24):16785–16793

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  75. Tesmer JJ, Nance MR, Singh P, Lee H (2012) Structure of a monomeric variant of rhodopsin kinase at 2.5 Å resolution. Acta Crystallogr 68(Pt 6):622–625

    CAS  Google Scholar 

  76. Palczewski K, Buczylko J, Lebioda L, Crabb JW, Polans AS (1993) Identification of the N-terminal region in rhodopsin kinase involved in its interaction with rhodopsin. J Biol Chem 268(8):6004–6013

    CAS  PubMed  Google Scholar 

  77. Orban T, Huang CC, Homan KT, Jastrzebska B, Tesmer JJ, Palczewski K (2012) Substrate-induced changes in the dynamics of rhodopsin kinase (G protein-coupled receptor kinase 1). Biochemistry 51(16):3404–3411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Boguth CA, Singh P, Huang CC, Tesmer JJ (2010) Molecular basis for activation of G protein-coupled receptor kinases. EMBO J 29(19):3249–3259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Huang CC, Yoshino-Koh K, Tesmer JJ (2009) A surface of the kinase domain critical for the allosteric activation of G protein-coupled receptor kinases. J Biol Chem 284(25):17206–17215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Pao CS, Barker BL, Benovic JL (2009) Role of the amino terminus of G protein-coupled receptor kinase 2 in receptor phosphorylation. Biochemistry 48(30):7325–7333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ni Q, Shaffer J, Adams JA (2000) Insights into nucleotide binding in protein kinase A using fluorescent adenosine derivatives. Protein Sci 9(9):1818–1827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Xu H, Jiang X, Shen K, Fischer CC, Wedegaertner PB (2014) 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 25(13):2105–2115

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  83. 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 

  84. Pulvermuller A, Palczewski K, Hofmann KP (1993) Interaction between photoactivated rhodopsin and its kinase: stability and kinetics of complex formation. Biochemistry 32(51):14082–14088

    Article  CAS  PubMed  Google Scholar 

  85. Palczewski K, McDowell JH, Hargrave PA (1988) Rhodopsin kinase: substrate specificity and factors that influence activity. Biochemistry 27(7):2306–2313

    Article  CAS  PubMed  Google Scholar 

  86. Shi W, Osawa S, Dickerson CD, Weiss ER (1995) Rhodopsin mutants discriminate sites important for the activation of rhodopsin kinase and Gt. J Biol Chem 270(5):2112–2119

    Article  CAS  PubMed  Google Scholar 

  87. Palczewski K, Buczylko J, Kaplan MW, Polans AS, Crabb JW (1991) Mechanism of rhodopsin kinase activation. J Biol Chem 266(20):12949–12955

    CAS  PubMed  Google Scholar 

  88. Kelleher DJ, Johnson GL (1990) Characterization of rhodopsin kinase purified from bovine rod outer segments. J Biol Chem 265(5):2632–2639

    CAS  PubMed  Google Scholar 

  89. Bayburt TH, Vishnivetskiy SA, McLean MA, Morizumi T, Huang CC, Tesmer JJG, Ernst OP, Sligar SG, Gurevich VV (2011) Monomeric rhodopsin is sufficient for normal rhodopsin kinase (GRK1) phosphorylation and arrestin-1 binding. J Biol Chem 286(2):1420–1428

    Article  CAS  PubMed  Google Scholar 

  90. Hanson SM, Gurevich EV, Vishnivetskiy SA, Ahmed MR, Song XF, Gurevich VV (2007) Each rhodopsin molecule binds its own arrestin. Proc Natl Acad Sci U S A 104(9):3125–3128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Jastrzebska B, Orban T, Golczak M, Engel A, Palczewski K (2013) Asymmetry of the rhodopsin dimer in complex with transducin. FASEB J 27(4):1572–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jastrzebska B, Ringler P, Lodowski DT, Moiseenkova-Bell V, Golczak M, Muller SA, Palczewski K, Engel A (2011) Rhodopsin-transducin heteropentamer: three-dimensional structure and biochemical characterization. J Struct Biol 176(3):387–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Jastrzebska B, Ringler P, Palczewski K, Engel A (2013) The rhodopsin-transducin complex houses two distinct rhodopsin molecules. J Struct Biol 182(2):164–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Jastrzebska B, Fotiadis D, Jang GF, Stenkamp RE, Engel A, Palczewski K (2006) Functional and structural characterization of rhodopsin oligomers. J Biol Chem 281(17):11917–11922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Huang CC, Orban T, Jastrzebska B, Palczewski K, Tesmer JJG (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 

  96. Gan X, Ma Z, Deng N, Wang J, Ding J, Li L (2004) Involvement of the C-terminal proline-rich motif of G protein-coupled receptor kinases in recognition of activated rhodopsin. J Biol Chem 279(48):49741–49746

    Article  CAS  PubMed  Google Scholar 

  97. 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(25):15333–15340

    CAS  PubMed  Google Scholar 

  98. Chen CK, Inglese J, Lefkowitz RJ, Hurley JB (1995) Ca(2+)-dependent interaction of recoverin with rhodopsin kinase. J Biol Chem 270(30):18060–18066

    Article  CAS  PubMed  Google Scholar 

  99. Clarke S (1992) Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Annu Rev Biochem 61:355–386

    Article  CAS  PubMed  Google Scholar 

  100. Zhao X, Yokoyama K, Whitten ME, Huang J, Gelb MH, Palczewski K (1999) A novel form of rhodopsin kinase from chicken retina and pineal gland. FEBS Lett 454(1–2):115–121

    Article  CAS  PubMed  Google Scholar 

  101. Inglese J, Koch WJ, Caron MG, Lefkowitz RJ (1992) Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. Nature 359(6391):147–150

    Article  CAS  PubMed  Google Scholar 

  102. Rando RR (1996) Chemical biology of protein isoprenylation/methylation. Biochim Biophys Acta 1300(1):5–16

    Article  PubMed  Google Scholar 

  103. Kutuzov MA, Andreeva AV, Bennett N (2012) Regulation of the methylation status of G protein-coupled receptor kinase 1 (rhodopsin kinase). Cell Signal 24(12):2259–2267

    Article  CAS  PubMed  Google Scholar 

  104. Lee RH, Brown BM, Lolley RN (1982) Autophosphorylation of rhodopsin kinase from retinal rod outer segments. Biochemistry 21(14):3303–3307

    Article  CAS  PubMed  Google Scholar 

  105. Buczylko J, Gutmann C, Palczewski K (1991) Regulation of rhodopsin kinase by autophosphorylation. Proc Natl Acad Sci U S A 88(6):2568–2572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Palczewski K, Buczylko J, Van Hooser P, Carr SA, Huddleston MJ, Crabb JW (1992) Identification of the autophosphorylation sites in rhodopsin kinase. J Biol Chem 267(26):18991–18998

    CAS  PubMed  Google Scholar 

  107. Horner TJ, Osawa S, Schaller MD, Weiss ER (2005) Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities. J Biol Chem 280(31):28241–28250

    Article  CAS  PubMed  Google Scholar 

  108. Osawa S, Jo R, Xiong Y, Reidel B, Tserentsoodol N, Arshavsky VY, Iuvone PM, Weiss ER (2011) Phosphorylation of G protein-coupled receptor kinase 1 (GRK1) is regulated by light but independent of phototransduction in rod photoreceptors. J Biol Chem 286(23):20923–20929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Klenchin VA, Calvert PD, Bownds MD (1995) Inhibition of rhodopsin kinase by recoverin. Further evidence for a negative feedback system in phototransduction. J Biol Chem 270(27):16147–16152

    Article  CAS  PubMed  Google Scholar 

  110. Calvert PD, Klenchin VA, Bownds MD (1995) Rhodopsin kinase inhibition by recoverin. Function of recoverin myristoylation. J Biol Chem 270(41):24127–24129

    Article  CAS  PubMed  Google Scholar 

  111. Senin II, Dean KR, Zargarov AA, Akhtar M, Philippov PP (1997) Recoverin inhibits the phosphorylation of dark-adapted rhodopsin more than it does that of bleached rhodopsin: a possible mechanism through which rhodopsin kinase is prevented from participation in a side reaction. Biochem J 321(Pt 2):551–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Kawamura S (1999) Calcium-dependent regulation of rhodopsin phosphorylation. Novartis Found Symp 224:208–218, discussion 218–224

    CAS  PubMed  Google Scholar 

  113. Makino CL, Dodd RL, Chen J, Burns ME, Roca A, Simon MI, Baylor DA (2004) Recoverin regulates light-dependent phosphodiesterase activity in retinal rods. J Gen Physiol 123(6):729–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Chen CK, Woodruff ML, Chen FS, Chen Y, Cilluffo MC, Tranchina D, Fain GL (2012) Modulation of mouse rod response decay by rhodopsin kinase and recoverin. J Neurosci 32(45):15998–16006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Sakurai K, Chen J, Khani SC, Kefalov VJ (2015) Regulation of mammalian cone phototransduction by recoverin and rhodopsin kinase. J Biol Chem 290(14):9239–9250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Higgins MK, Oprian DD, Schertler GF (2006) Recoverin binds exclusively to an amphipathic peptide at the N terminus of rhodopsin kinase, inhibiting rhodopsin phosphorylation without affecting catalytic activity of the kinase. J Biol Chem 281(28):19426–19432

    Article  CAS  PubMed  Google Scholar 

  117. Ames JB, Levay K, Wingard JN, Lusin JD, Slepak VZ (2006) Structural basis for calcium-induced inhibition of rhodopsin kinase by recoverin. J Biol Chem 281(48):37237–37245

    Article  CAS  PubMed  Google Scholar 

  118. Torisawa A, Arinobu D, Tachibanaki S, Kawamura S (2008) Amino acid residues in GRK1/GRK7 responsible for interaction with S-modulin/recoverin. Photochem Photobiol 84(4):823–830

    Article  CAS  PubMed  Google Scholar 

  119. Chen CKJ (2002) Recoverin and rhodopsin kinase. Photoreceptors Calcium 514:101–107

    Article  CAS  Google Scholar 

  120. Zernii EY, Komolov KE, Permyakov SE, Kolpakova T, Dell’Orco D, Poetzsch A, Knyazeva EL, Grigoriev II, Permyakov EA, Senin II, Philippov PP, Koch KW (2011) Involvement of the recoverin C-terminal segment in recognition of the target enzyme rhodopsin kinase. Biochem J 435:441–450

    Article  CAS  PubMed  Google Scholar 

  121. Komolov KE, Zinchenko DV, Churumova VA, Vaganova SA, Weiergraber OH, Senin II, Philippov PP, Koch KW (2005) One of the Ca2+ binding sites of recoverin exclusively controls interaction with rhodopsin kinase. Biol Chem 386(3):285–289

    Article  CAS  PubMed  Google Scholar 

  122. Iacovelli L, Sallese M, Mariggio S, De Blasi A (1999) Regulation of G-protein-coupled receptor kinase subtypes by calcium sensor proteins. FASEB J 13(1):1–8

    CAS  PubMed  Google Scholar 

  123. Senin II, Zargarov AA, Alekseev AM, Gorodovikova EN, Lipkin VM, Philippov PP (1995) N-myristoylation of recoverin enhances its efficiency as an inhibitor of rhodopsin kinase. FEBS Lett 376(1-2):87–90

    Article  CAS  PubMed  Google Scholar 

  124. Tachibanaki S, Nanda K, Sasaki K, Ozaki K, Kawamura S (2000) Amino acid residues of S-modulin responsible for interaction with rhodopsin kinase. J Biol Chem 275(5):3313–3319

    Article  CAS  PubMed  Google Scholar 

  125. Levay K, Satpaev DK, Pronin AN, Benovic JL, Slepak VZ (1998) Localization of the sites for Ca2 + -binding proteins on G protein-coupled receptor kinases. Biochemistry 37(39):13650–13659

    Article  CAS  PubMed  Google Scholar 

  126. Pronin AN, Satpaev DK, Slepak VZ, Benovic JL (1997) Regulation of G protein-coupled receptor kinases by calmodulin and localization of the calmodulin binding domain. J Biol Chem 272(29):18273–18280

    Article  CAS  PubMed  Google Scholar 

  127. Chuang TT, Paolucci L, DeBlasi A (1996) Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin. J Biol Chem 271(45):28691–28696

    Article  CAS  PubMed  Google Scholar 

  128. Grigoriev II, Senin II, Tikhomirova NK, Komolov KE, Permyakov SE, Zernii EY, Koch KW, Philippov PP (2012) Synergetic effect of recoverin and calmodulin on regulation of rhodopsin kinase. Front Mol Neurosci 5:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Arinobu D, Tachibanaki S, Kawamura S (2010) Larger inhibition of visual pigment kinase in cones than in rods. J Neurochem 115(1):259–268

    Article  CAS  PubMed  Google Scholar 

  130. Bruel C, Cha K, Niu L, Reeves PJ, Khorana HG (2000) Rhodopsin kinase: two mAbs binding near the carboxyl terminus cause time-dependent inactivation. Proc Natl Acad Sci U S A 97(7):3010–3015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Carman CV, Lisanti MP, Benovic JL (1999) Regulation of G protein-coupled receptor kinases by caveolin. J Biol Chem 274(13):8858–8864

    Article  CAS  PubMed  Google Scholar 

  132. Berta AI, Boesze-Battaglia K, Magyar A, Szel A, Kiss AL (2011) Localization of caveolin-1 and c-src in mature and differentiating photoreceptors: raft proteins co-distribute with rhodopsin during development. J Mol Histol 42(6):523–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Lebioda L, Hargrave PA, Palczewski K (1990) X-ray crystal-structure of sangivamycin, a potent inhibitor of protein-kinases. FEBS Lett 266(1-2):102–104

    Article  CAS  PubMed  Google Scholar 

  134. Palczewski K, Kahn N, Hargrave PA (1990) Nucleoside inhibitors of rhodopsin kinase. Biochemistry 29(26):6276–6282

    Article  CAS  PubMed  Google Scholar 

  135. Homan KT, Larimore KM, Elkins JM, Szklarz M, Knapp S, Tesmer JJ (2015) Identification and structure-function analysis of subfamily selective g protein-coupled receptor kinase inhibitors. ACS Chem Biol 10(1):310–319

    Article  CAS  PubMed  Google Scholar 

  136. Homan KT, Wu E, Cannavo A, Koch WJ, Tesmer JJ (2014) Identification and characterization of amlexanox as a G protein-coupled receptor kinase 5 inhibitor. Molecules 19(10):16937–16949

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Thal DM, Homan KT, Chen J, Wu EK, Hinkle PM, Huang ZM, Chuprun JK, Song J, Gao E, Cheung JY, Sklar LA, Koch WJ, Tesmer JJ (2012) Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility. ACS Chem Biol 7(11):1830–1839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. 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 beta2 adrenergic receptor-Gs protein complex. Nature 477(7366):549–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Drs. Leslie T. Webster Jr., and members of Palczewski laboratory for helpful comments on this manuscript. This work was supported by funding from the National Institutes of Health EY009339 (KP), EY025451 (KP), the Arnold and Mabel Beckman Foundation (KP), the Canadian Institute for Advanced Research (CIFAR), and the Foundation Fighting Blindness (KP). K.P. is John H. Hord Professor of Pharmacology.

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  1. Department of Pharmacology, School of Medicine, Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106-4965, USA

    Tivadar Orban & Krzysztof Palczewski

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  1. Tivadar Orban
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  2. Krzysztof Palczewski
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Correspondence to Krzysztof Palczewski .

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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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Orban, T., Palczewski, K. (2016). Structure and Function of G-Protein-Coupled Receptor Kinases 1 and 7. 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_2

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