1932

Abstract

Abstract

Upon their discovery, β-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows that β-arrestins can also function to activate signaling cascades independently of G protein activation. By serving as multiprotein scaffolds, the β-arrestins bring elements of specific signaling pathways into close proximity. β-Arrestin regulation has been demonstrated for an ever-increasing number of signaling molecules, including the mitogen-activated protein kinases ERK, JNK, and p38 as well as Akt, PI3 kinase, and RhoA. In addition, investigators are discovering new roles for β-arrestins in nuclear functions. Here, we review the signaling capacities of these versatile adapter molecules and discuss the possible implications for cellular processes such as chemotaxis and apoptosis.

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2007-03-17
2024-06-12
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Literature Cited

  1. Lefkowitz RJ. 2004. Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol. Sci. 25:413–22 [Google Scholar]
  2. Pitcher JA, Freedman NJ, Lefkowitz RJ. 1998. G protein-coupled receptor kinases. Annu. Rev. Biochem. 67:653–92 [Google Scholar]
  3. Pao CS, Benovic JL. 2002. Phosphorylation-independent desensitization of G protein-coupled receptors. Sci. STKE 2002:PE42 [Google Scholar]
  4. Penela P, Ribas C, Mayor F Jr. 2003. Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases. Cell Signal. 15:973–81 [Google Scholar]
  5. Benovic JL, Kuhn H, Weyand I, Codina J, Caron MG, Lefkowitz RJ. 1987. Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc. Natl. Acad. Sci. USA 84:8879–82 [Google Scholar]
  6. Pfister C, Chabre M, Plouet J, Tuyen VV, De Kozak Y. et al. 1985. Retinal S antigen identified as the 48K protein regulating light-dependent phosphodiesterase in rods. Science 228:891–93 [Google Scholar]
  7. Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. 1990. β-Arrestin: a protein that regulates β-adrenergic receptor function. Science 248:1547–50 [Google Scholar]
  8. Attramadal H, Arriza JL, Aoki C, Dawson TM, Codina J. et al. 1992. Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. J. Biol. Chem. 267:17882–90 [Google Scholar]
  9. Moore CAC, Milano SK, Benovic J. 2007. Regulation of receptor trafficking by GRKs and arrestins. Annu. Rev. Physiol. 69: in press [Google Scholar]
  10. Krupnick JG, Goodman OB, Jr., Keen JH, Benovic JL. 1997. Arrestin/clathrin interaction. Localization of the clathrin binding domain of nonvisual arrestins to the carboxy terminus. J. Biol. Chem. 272:15011–16 [Google Scholar]
  11. Goodman OB Jr, Krupnick JG, Santini F, Gurevich VV, Penn RB. et al. 1996. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor. Nature 383:447–50 [Google Scholar]
  12. Laporte SA, Miller WE, Kim KM, Caron MG. 2002. β-Arrestin/AP-2 interaction in G protein-coupled receptor internalization: identification of a β-arrestin binding site in β2-adaptin. J. Biol. Chem. 277:9247–54 [Google Scholar]
  13. Mukherjee S, Casanova JE, Hunzicker-Dunn M. 2001. Desensitization of the luteinizing hormone/choriogonadotropin receptor in ovarian follicular membranes is inhibited by catalytically inactive ARNO+. J. Biol. Chem. 276:6524–28 [Google Scholar]
  14. Claing A, Chen W, Miller WE, Vitale N, Moss J. et al. 2001. β-Arrestin-mediated ADP-ribosylation factor 6 activation and β2-adrenergic receptor endocytosis. J. Biol. Chem. 276:42509–13 [Google Scholar]
  15. Conner DA, Mathier MA, Mortensen RM, Christe M, Vatner SF. et al. 1997. β-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to β-adrenergic stimulation. Circ. Res. 81:1021–26 [Google Scholar]
  16. Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT. 1999. Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science 286:2495–98 [Google Scholar]
  17. Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ. 2001. β-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc. Natl. Acad. Sci. USA 98:1601–6 [Google Scholar]
  18. Oakley RH, Laporte SA, Holt JA, Caron MG, Barak LS. 2000. Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J. Biol. Chem. 275:17201–10 [Google Scholar]
  19. Paing MM, Stutts AB, Kohout TA, Lefkowitz RJ, Trejo J. 2002. β-Arrestins regulate protease-activated receptor-1 desensitization but not internalization or down-regulation. J. Biol. Chem. 277:1292–300 [Google Scholar]
  20. Lin FT, Miller WE, Luttrell LM, Lefkowitz RJ. 1999. Feedback regulation of beta-arrestin1 function by extracellular signal-regulated kinases. J. Biol. Chem. 274:15971–74 [Google Scholar]
  21. Kim YM, Barak LS, Caron MG, Benovic JL. 2002. Regulation of arrestin-3 phosphorylation by casein kinase II. J. Biol. Chem. 277:16837–46 [Google Scholar]
  22. Lin FT, Chen W, Shenoy S, Cong M, Exum ST, Lefkowitz RJ. 2002. Phosphorylation of β-arrestin2 regulates its function in internalization of β2-adrenergic receptors. Biochemistry 41:10692–99 [Google Scholar]
  23. Lin FT, Krueger KM, Kendall HE, Daaka Y, Fredericks ZL. et al. 1997. Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. J. Biol. Chem. 272:31051–57 [Google Scholar]
  24. Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ. 2001. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science 294:1307–13 [Google Scholar]
  25. Shenoy SK, Lefkowitz RJ. 2003. Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J. Biol. Chem. 278:14498–506 [Google Scholar]
  26. Shenoy SK, Lefkowitz RJ. 2005. Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes. J. Biol. Chem. 280:15315–24 [Google Scholar]
  27. Perroy J, Pontier S, Charest PG, Aubry M, Bouvier M. 2004. Real-time monitoring of ubiquitination in living cells by BRET. Nat. Methods 1:203–8 [Google Scholar]
  28. Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA. 1980. Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc. Natl. Acad. Sci. USA 77:1783–86 [Google Scholar]
  29. Haas AL, Warms JV, Hershko A, Rose IA. 1982. Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation. J. Biol. Chem. 257:2543–48 [Google Scholar]
  30. Hicke L, Dunn R. 2003. Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu. Rev. Cell Dev. Biol. 19:141–72 [Google Scholar]
  31. Shenoy SK, Lefkowitz RJ. 2003. Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling. Biochem. J. 375:503–15 [Google Scholar]
  32. Welchman RL, Gordon C, Mayer RJ. 2005. Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat. Rev. Mol. Cell Biol. 6:599–609 [Google Scholar]
  33. Wojcikiewicz RJ. 2004. Regulated ubiquitination of proteins in GPCR-initiated signaling pathways. Trends Pharmacol. Sci. 25:35–41 [Google Scholar]
  34. Chen ZJ. 2005. Ubiquitin signalling in the NF-κB pathway. Nat. Cell Biol. 7:758–65 [Google Scholar]
  35. Martin NP, Lefkowitz RJ, Shenoy SK. 2003. Regulation of V2 vasopressin receptor degradation by agonist-promoted ubiquitination. J. Biol. Chem. 278:45954–59 [Google Scholar]
  36. Marchese A, Benovic JL. 2001. Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J. Biol. Chem. 276:45509–12 [Google Scholar]
  37. Marchese A, Raiborg C, Santini F, Keen JH, Stenmark H, Benovic JL. 2003. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev. Cell 5:709–22 [Google Scholar]
  38. Jacob C, Cottrell GS, Gehringer D, Schmidlin F, Grady EF, Bunnett NW. 2005. c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2. J. Biol. Chem. 280:16076–87 [Google Scholar]
  39. Girnita L, Girnita A, Larsson O. 2003. Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor. Proc. Natl. Acad. Sci. USA 100:8247–52 [Google Scholar]
  40. Girnita L, Shenoy SK, Sehat B, Vasilcanu R, Girnita A. et al. 2005. β-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. J. Biol. Chem. 280:24412–19 [Google Scholar]
  41. Mukherjee A, Veraksa A, Bauer A, Rosse C, Camonis J, Artavanis-Tsakonas S. 2005. Regulation of Notch signalling by non-visual beta-arrestin. Nat. Cell Biol. 7:1191–201 [Google Scholar]
  42. Herranz S, Rodriguez JM, Bussink HJ, Sanchez-Ferrero JC, Arst HN Jr. et al. 2005. Arrestin-related proteins mediate pH signaling in fungi. Proc. Natl. Acad. Sci. USA 102:12141–46 [Google Scholar]
  43. Katzmann DJ, Odorizzi G, Emr SD. 2002. Receptor downregulation and multivesicular-body sorting. Nat. Rev. Mol. Cell Biol. 3:893–905 [Google Scholar]
  44. Luttrell LM, Daaka Y, Della Rocca GJ, Lefkowitz RJ. 1997. G protein-coupled receptors mediate two functionally distinct pathways of tyrosine phosphorylation in rat 1a fibroblasts. Shc phosphorylation and receptor endocytosis correlate with activation of Erk kinases. J. Biol. Chem. 272:31648–56 [Google Scholar]
  45. Lin FT, Daaka Y, Lefkowitz RJ. 1998. β-Arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor. J. Biol. Chem. 273:31640–43 [Google Scholar]
  46. Daaka Y, Luttrell LM, Ahn S, Della Rocca GJ, Ferguson SS. et al. 1998. Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J. Biol. Chem. 273:685–88 [Google Scholar]
  47. Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S. et al. 1999. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283:655–61 [Google Scholar]
  48. DeFea KA, Vaughn ZD, O'Bryan EM, Nishijima D, Dery O, Bunnett NW. 2000. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta-arrestin-dependent scaffolding complex. Proc. Natl. Acad. Sci. USA 97:11086–91 [Google Scholar]
  49. Miller WE, Maudsley S, Ahn S, Khan KD, Luttrell LM, Lefkowitz RJ. 2000. Beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis. J. Biol. Chem. 275:11312–19 [Google Scholar]
  50. DeFea KA, Zalevsky J, Thoma MS, Dery O, Mullins RD, Bunnett NW. 2000. Beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol 148:1267–81 [Google Scholar]
  51. Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME. et al. 2001. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc. Natl. Acad. Sci. USA 98:2449–54 [Google Scholar]
  52. Scott MG, Pierotti V, Storez H, Lindberg E, Thuret A. et al. 2006. Cooperative regulation of extracellular signal-regulated kinase activation and cell shape change by filamin A and β-arrestins. Mol. Cell Biol. 26:3432–45 [Google Scholar]
  53. Tohgo A, Pierce KL, Choy EW, Lefkowitz RJ, Luttrell LM. 2002. β-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J. Biol. Chem. 277:9429–36 [Google Scholar]
  54. Tohgo A, Choy EW, Gesty-Palmer D, Pierce KL, Laporte S. et al. 2003. The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation. J. Biol. Chem. 278:6258–67 [Google Scholar]
  55. Barnes WG, Reiter E, Violin JD, Ren XR, Milligan G, Lefkowitz RJ. 2005. β-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. J. Biol. Chem. 280:8041–50 [Google Scholar]
  56. Ge L, Ly Y, Hollenberg M, DeFea K. 2003. A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J. Biol. Chem. 278:34418–26 [Google Scholar]
  57. Hunton DL, Barnes WG, Kim J, Ren XR, Violin JD. et al. 2005. Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxis. Mol. Pharmacol. 67:1229–36 [Google Scholar]
  58. Ahn S, Nelson CD, Garrison TR, Miller WE, Lefkowitz RJ. 2003. Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference. Proc. Natl. Acad. Sci. USA 100:1740–44 [Google Scholar]
  59. Ahn S, Shenoy SK, Wei H, Lefkowitz RJ. 2004. Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor. J. Biol. Chem. 279:35518–25 [Google Scholar]
  60. Lefkowitz RJ, Shenoy SK. 2005. Transduction of receptor signals by beta-arrestins. Science 308:512–17 [Google Scholar]
  61. Ahn S, Wei H, Garrison TR, Lefkowitz RJ. 2004. Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2. J. Biol. Chem. 279:7807–11 [Google Scholar]
  62. Ren XR, Reiter E, Ahn S, Kim J, Chen W, Lefkowitz RJ. 2005. Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor. Proc. Natl. Acad. Sci. USA 102:1448–53 [Google Scholar]
  63. Shenoy SK, Drake MT, Nelson CD, Houtz DA, Xiao K. et al. 2006. Beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor. J. Biol. Chem. 281:1261–73 [Google Scholar]
  64. Gesty-Palmer D, Chen M, Reiter E, Ahn S, Nelson CD. et al. 2006. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J. Biol. Chem. 281:10856–64 [Google Scholar]
  65. Gaborik Z, Jagadeesh G, Zhang M, Spat A, Catt KJ, Hunyady L. 2003. The role of a conserved region of the second intracellular loop in AT1 angiotensin receptor activation and signaling. Endocrinology 144:2220–28 [Google Scholar]
  66. Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L. et al. 2003. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc. Natl. Acad. Sci. USA 100:10782–87 [Google Scholar]
  67. Holloway AC, Qian H, Pipolo L, Ziogas J, Miura S. et al. 2002. Side-chain substitutions within angiotensin II reveal different requirements for signaling, internalization, and phosphorylation of type 1A angiotensin receptors. Mol. Pharmacol. 61:768–77 [Google Scholar]
  68. Yee DK, Suzuki A, Luo L, Fluharty SJ. 2006. Identification of structural determinants for G-protein independent activation of mitogen activated protein kinases in the seventh transmembrane domain of the angiotensin II type 1 receptor. Mol. Endocrinol. 20:(8)1924–34 [Google Scholar]
  69. Daniels D, Yee DK, Faulconbridge LF, Fluharty SJ. 2005. Divergent behavioral roles of angiotensin receptor intracellular signaling cascades. Endocrinology 146:5552–60 [Google Scholar]
  70. O'Donnell SR, Wanstall JC. 1980. Evidence that ICI 118551 is a potent, highly beta 2-selective adrenoceptor antagonist and can be used to characterize beta-adrenoceptor populations in tissues. Life Sci. 27:671–77 [Google Scholar]
  71. Azzi M, Charest PG, Angers S, Rousseau G, Kohout T. et al. 2003. Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc. Natl. Acad. Sci. USA 100:11406–11 [Google Scholar]
  72. Kohout TA, Nicholas SL, Perry SJ, Reinhart G, Junger S, Struthers RS. 2004. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J. Biol. Chem. 279:23214–22 [Google Scholar]
  73. Sun Y, Cheng Z, Ma L, Pei G. 2002. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J. Biol. Chem. 277:49212–19 [Google Scholar]
  74. Jiang Q, Yan Z, Feng J. 2006. Activation of group III metabotropic glutamate receptors attenuates rotenone toxicity on dopaminergic neurons through a microtubule-dependent mechanism. J. Neurosci. 26:4318–28 [Google Scholar]
  75. Mohit AA, Martin JH, Miller CA. 1995. p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system. Neuron 14:67–78 [Google Scholar]
  76. McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME. et al. 2000. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290:1574–77 [Google Scholar]
  77. Miller WE, McDonald PH, Cai SF, Field ME, Davis RJ, Lefkowitz RJ. 2001. Identification of a motif in the carboxyl terminus of beta-arrestin2 responsible for activation of JNK3. J. Biol. Chem. 276:27770–77 [Google Scholar]
  78. Scott MG, Le Rouzic E, Perianin A, Pierotti V, Enslen H. et al. 2002. Differential nucleocytoplasmic shuttling of beta-arrestins. Characterization of a leucine-rich nuclear export signal in beta-arrestin2. J. Biol. Chem. 277:37693–701 [Google Scholar]
  79. Willoughby EA, Collins MK. 2005. Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2. J. Biol. Chem. 280:25651–58 [Google Scholar]
  80. Miller WE, Houtz DA, Nelson CD, Kolattukudy PE, Lefkowitz RJ. 2003. G-protein-coupled receptor (GPCR) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCR. J. Biol. Chem. 278:21663–71 [Google Scholar]
  81. Bruchas MR, Macey TA, Lowe JD, Chavkin C. 2006. Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. J. Biol. Chem. 281:18081–89 [Google Scholar]
  82. Povsic TJ, Kohout TA, Lefkowitz RJ. 2003. Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis. J. Biol. Chem. 278:51334–39 [Google Scholar]
  83. Goel R, Phillips-Mason PJ, Raben DM, Baldassare JJ. 2002. α-Thrombin induces rapid and sustained Akt phosphorylation by β-arrestin1-dependent and -independent mechanisms, and only the sustained Akt phosphorylation is essential for G1 phase progression. J. Biol. Chem. 277:18640–48 [Google Scholar]
  84. Goel R, Baldassare JJ. 2002. β-Arrestin 1 couples thrombin to the rapid activation of the Akt pathway. Ann. NY Acad. Sci. 973:138–41 [Google Scholar]
  85. Goel R, Phillips-Mason PJ, Gardner A, Raben DM, Baldassare JJ. 2004. α-Thrombin-mediated phosphatidylinositol 3-kinase activation through release of Gβγ dimers from Gαq and Gαi2. J. Biol. Chem. 279:6701–10 [Google Scholar]
  86. Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG. 2005. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122:261–73 [Google Scholar]
  87. Sen R, Baltimore D. 1986. Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47:921–28 [Google Scholar]
  88. Karin M, Greten FR. 2005. NF-κB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5:749–59 [Google Scholar]
  89. Witherow DS, Garrison TR, Miller WE, Lefkowitz RJ. 2004. β-Arrestin inhibits NF-κB activity by means of its interaction with the NF-κB inhibitor IκBα. Proc. Natl. Acad. Sci. USA 101:8603–7 [Google Scholar]
  90. Gao H, Sun Y, Wu Y, Luan B, Wang Y. et al. 2004. Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-κB pathways. Mol Cell 14:303–17 [Google Scholar]
  91. Luan B, Zhang Z, Wu Y, Kang J, Pei G. 2005. Beta-arrestin2 functions as a phosphorylation-regulated suppressor of UV-induced NF-κB activation. EMBO J. 24:4237–46 [Google Scholar]
  92. Gesty-Palmer D, Shewy HE, Kohout TA, Luttrell LM. 2005. β-Arrestin 2 expression determines the transcriptional response to lysophosphatidic acid stimulation in murine embryo fibroblasts. J. Biol. Chem. 280:32157–67 [Google Scholar]
  93. Piu F, Gauthier NK, Wang F. 2006. Beta-arrestin 2 modulates the activity of nuclear receptor RAR beta2 through activation of ERK2 kinase. Oncogene 25:218–29 [Google Scholar]
  94. Kang J, Shi Y, Xiang B, Qu B, Su W. et al. 2005. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell 123:833–47 [Google Scholar]
  95. Puig J, Arendt A, Tomson FL, Abdulaeva G, Miller R. et al. 1995. Synthetic phosphopeptide from rhodopsin sequence induces retinal arrestin binding to photoactivated unphosphorylated rhodopsin. FEBS Lett. 362:185–88 [Google Scholar]
  96. McDowell JH, Smith WC, Miller RL, Popp MP, Arendt A. et al. 1999. Sulfhydryl reactivity demonstrates different conformational states for arrestin, arrestin activated by a synthetic phosphopeptide, and constitutively active arrestin. Biochemistry 38:6119–25 [Google Scholar]
  97. Gurevich VV, Gurevich EV. 2004. The molecular acrobatics of arrestin activation. Trends Pharmacol. Sci. 25:105–11 [Google Scholar]
  98. Granzin J, Wilden U, Choe HW, Labahn J, Krafft B, Buldt G. 1998. X-ray crystal structure of arrestin from bovine rod outer segments. Nature 391:918–21 [Google Scholar]
  99. Han M, Gurevich VV, Vishnivetskiy SA, Sigler PB, Schubert C. 2001. Crystal structure of beta-arrestin at 1.9 Å: possible mechanism of receptor binding and membrane translocation. Structure 9:869–80 [Google Scholar]
  100. Hirsch JA, Schubert C, Gurevich VV, Sigler PB. 1999. The 2.8 Å crystal structure of visual arrestin: a model for arrestin's regulation. Cell 97:257–69 [Google Scholar]
  101. Milano SK, Pace HC, Kim YM, Brenner C, Benovic JL. 2002. Scaffolding functions of arrestin-2 revealed by crystal structure and mutagenesis. Biochemistry 41:3321–28 [Google Scholar]
  102. 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. 274:11451–54 [Google Scholar]
  103. Xiao K, Shenoy SK, Nobles K, Lefkowitz RJ. 2004. Activation-dependent conformational changes in beta-arrestin 2. J. Biol. Chem. 279:55744–53 [Google Scholar]
  104. Charest PG, Terrillon S, Bouvier M. 2005. Monitoring agonist-promoted conformational changes of beta-arrestin in living cells by intramolecular BRET. EMBO Rep. 6:334–40 [Google Scholar]
  105. Terrillon S, Bouvier M. 2004. Receptor activity-independent recruitment of beta-arrestin2 reveals specific signalling modes. EMBO J. 23:3950–61 [Google Scholar]
  106. Gurevich VV, Benovic JL. 1995. Visual arrestin binding to rhodopsin. Diverse functional roles of positively charged residues within the phosphorylation-recognition region of arrestin. J. Biol. Chem. 270:6010–16 [Google Scholar]
  107. Kovoor A, Celver J, Abdryashitov RI, Chavkin C, Gurevich VV. 1999. Targeted construction of phosphorylation-independent beta-arrestin mutants with constitutive activity in cells. J. Biol. Chem. 274:6831–34 [Google Scholar]
  108. Chen W, Hu LA, Semenov MV, Yanagawa S, Kikuchi A. et al. 2001. β-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. Proc. Natl. Acad. Sci. USA 98:14889–94 [Google Scholar]
  109. Chen W, Ren XR, Nelson CD, Barak LS, Chen JK. et al. 2004. Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science 306:2257–60 [Google Scholar]
  110. Chen W, Kirkbride KC, How T, Nelson CD, Mo J. et al. 2003. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science 301:1394–97 [Google Scholar]
  111. Wu JH, Peppel K, Nelson CD, Lin FT, Kohout TA. et al. 2003. The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor. J. Biol. Chem. 278:44238–45 [Google Scholar]
  112. Szabo EZ, Numata M, Lukashova V, Iannuzzi P, Orlowski J. 2005. β-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform. Proc. Natl. Acad. Sci. USA 102:2790–95 [Google Scholar]
  113. Wang Y, Tang Y, Teng L, Wu Y, Zhao X, Pei G. 2006. Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. Nat. Immunol. 7:139–47 [Google Scholar]
  114. Devi LA. 2001. Heterodimerization of G-protein-coupled receptors: pharmacology, signaling and trafficking. Trends Pharmacol. Sci. 22:532–37 [Google Scholar]
  115. Terrillon S, Bouvier M. 2004. Roles of G-protein-coupled receptor dimerization. EMBO Rep. 5:30–34 [Google Scholar]
  116. Lee SJ, Montell C. 2004. Light-dependent translocation of visual arrestin regulated by the NINAC myosin III. Neuron 43:95–103 [Google Scholar]
  117. Lee SJ, Xu H, Kang LW, Amzel LM, Montell C. 2003. Light adaptation through phosphoinositide-regulated translocation of Drosophila visual arrestin. Neuron 39:121–32 [Google Scholar]
  118. Strissel KJ, Arshavsky VY. 2004. Myosin III illuminates the mechanism of arrestin translocation. Neuron 43:2–4 [Google Scholar]
  119. Gaidarov I, Krupnick JG, Falck JR, Benovic JL, Keen JH. 1999. Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. EMBO J. 18:871–81 [Google Scholar]
  120. Milano SK, Kim YM, Stefano FP, Benovic JL, Brenner C. 2006. Nonvisual arrestin oligomerization and cellular localization are regulated by inositol hexakisphosphate binding. J. Biol. Chem. 281:9812–23 [Google Scholar]
  121. Storez H, Scott MG, Issafras H, Burtey A, Benmerah A. et al. 2005. Homo- and hetero-oligomerization of beta-arrestins in living cells. J. Biol. Chem. 280:40210–15 [Google Scholar]
  122. Varadan R, Assfalg M, Haririnia A, Raasi S, Pickart C, Fushman D. 2004. Solution conformation of Lys63-linked di-ubiquitin chain provides clues to functional diversity of polyubiquitin signaling. J. Biol. Chem. 279:7055–63 [Google Scholar]
  123. Kuo FT, Lu TL, Fu HW. 2006. Opposing effects of beta-arrestin1 and beta-arrestin2 on activation and degradation of Src induced by protease-activated receptor 1. Cell Signal. In press [Google Scholar]
  124. Qian H, Pipolo L, Thomas WG. 1999. Identification of protein kinase C phosphorylation sites in the angiotensin II (AT1A) receptor. Biochem. J. 343:(Pt. 3)637–44 [Google Scholar]
  125. Milasta S, Evans NA, Ormiston L, Wilson S, Lefkowitz RJ, Milligan G. 2005. The sustainability of interactions between the orexin-1 receptor and beta-arrestin-2 is defined by a single C-terminal cluster of hydroxy amino acids and modulates the kinetics of ERK MAPK regulation. Biochem. J. 387:573–84 [Google Scholar]
  126. Stalheim L, Ding Y, Gullapalli A, Paing MM, Wolfe BL. et al. 2005. Multiple independent functions of arrestins in the regulation of protease-activated receptor-2 signaling and trafficking. Mol. Pharmacol. 67:78–87 [Google Scholar]
  127. Bohn LM, Gainetdinov RR, Sotnikova TD, Medvedev IO, Lefkowitz RJ. et al. 2003. Enhanced rewarding properties of morphine, but not cocaine, in β-arrestin-2 knock-out mice. J. Neurosci. 23:10265–73 [Google Scholar]
  128. Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG. 2000. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408:720–23 [Google Scholar]
  129. Wang Q, Zhao J, Brady AE, Feng J, Allen PB. et al. 2004. Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors. Science 304:1940–94 [Google Scholar]
  130. Morris M, Li P, Callahan MF, Oliverio MI, Coffman TM. et al. 1999. Neuroendocrine effects of dehydration in mice lacking the angiotensin AT1a receptor. Hypertension 33:482–86 [Google Scholar]
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  • Article Type: Review Article
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