Journal of Molecular and Cellular Cardiology
Volume 46, Issue 3 , Pages 300-308 , March 2009

Physiologic and cardiac roles of β-arrestins

  • Priyesh A. Patel

      Affiliations

    • Duke University School of Medicine, USA
  • ,
  • Douglas G. Tilley

      Affiliations

    • Duke University Department of Medicine, USA
  • ,
  • Howard A. Rockman

      Affiliations

    • Duke University Department of Medicine, USA
    • Duke University Department of Cell Biology and Genetics, USA
    • Corresponding Author InformationCorresponding author. Department of Medicine, Duke University Medical Center, DUMC 3104, 226 CARL Building, Research Drive, Durham, North Carolina 27710, USA. Fax: +1 919 668 2524.

Received 13 August 2008 ,Revised 10 November 2008 ,Accepted 12 November 2008.

References 

  1. Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by beta-arrestins. Science. 2005 Apr 22;308(5721):512–517
  2. Freedman NJ, Liggett SB, Drachman DE, Pei G, Caron MG, Lefkowitz RJ. Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase. J. Biol. Chem. 1995 Jul 28;270(30):17953–17961
  3. Moore CA, Milano SK, Benovic JL. Regulation of receptor trafficking by GRKs and arrestins. Annu. Rev. Physiol. 2007;69:451–482
  4. Benovic JL, Kuhn H, Weyand I, Codina J, Caron MG, Lefkowitz RJ. 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. U. S. A. 1987 Dec;84(24):8879–8882
  5. Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science. 1990 Jun 22;248(4962):1547–1550
  6. Wilden U, Hall SW, Kuhn H. 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. 1986 Mar;83(5):1174–1178
  7. Lohse MJ, Andexinger S, Pitcher J, Trukawinski S, Codina J, Faure JP, et al. 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. 1992 Apr 25;267(12):8558–8564
  8. Rajagopal K, Lefkowitz RJ, Rockman HA. When 7 transmembrane receptors are not G protein-coupled receptors. J. Clin. Invest. 2005 Nov;115(11):2971–2974
  9. Perry SJ, Baillie GS, Kohout TA, McPhee I, Magiera MM, Ang KL, et al. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science. 2002 Oct 25;298(5594):834–836
  10. Nelson CD, Perry SJ, Regier DS, Prescott SM, Topham MK, Lefkowitz RJ. Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestins. Science. 2007 Feb 2;315(5812):663–666
  11. Lynch MJ, Baillie GS, Mohamed A, Li X, Maisonneuve C, Klussmann E, et al. RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells. J. Biol. Chem. 2005 Sep 30;280(39):33178–33189
  12. Howe AK. Regulation of actin-based cell migration by cAMP/PKA. Biochim. Biophys. Acta. 2004 Jul 5;1692(2–3):159–174
  13. Salazar NC, Chen J, Rockman HA. Cardiac GPCRs: GPCR signaling in healthy and failing hearts. Biochim. Biophys. Acta. 2007 Apr;1768(4):1006–1018
  14. Lee KA. Transcriptional regulation by cAMP. Curr. Opin. Cell Biol. 1991 Dec;3(6):953–959
  15. Daaka Y, Luttrell LM, Lefkowitz RJ. Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature. 1997 Nov 6;390(6655):88–91
  16. Sakane F, Kanoh H. Molecules in focus: diacylglycerol kinase. Int. J. Biochem. Cell Biol. 1997 Oct;29(10):1139–1143
  17. Tan CM, Brady AE, Nickols HH, Wang Q, Limbird LE. Membrane trafficking of G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 2004;44:559–609
  18. Ferguson SS, Downey WE, Colapietro AM, Barak LS, Menard L, Caron MG. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science. 1996 Jan 19;271(5247):363–366
  19. Goodman OB, Krupnick JG, Santini F, Gurevich VV, Penn RB, Gagnon AW, et al. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor. Nature. 1996 Oct 3;383(6599):447–450
  20. Kim YM, Benovic JL. Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2 in G protein-coupled receptor trafficking. J. Biol. Chem. 2002 Aug 23;277(34):30760–30768
  21. Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, et al. The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc. Natl. Acad. Sci. U. S. A. 1999 Mar 30;96(7):3712–3717
  22. Gaidarov I, Krupnick JG, Falck JR, Benovic JL, Keen JH. Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. EMBO J. 1999 Feb 15;18(4):871–881
  23. Naga Prasad SV, Jayatilleke A, Madamanchi A, Rockman HA. Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis. Nat. Cell Biol. 2005 Aug;7(8):785–796
  24. D'Souza-Schorey C, Chavrier P. ARF proteins: roles in membrane traffic and beyond. Nat. Rev. Mol. Cell. Biol. 2006 May;7(5):347–358
  25. Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, et al. beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Proc. Natl. Acad. Sci. U. S. A. 1998 Nov 24;95(24):14082–14087
  26. Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ. The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing. J. Biol. Chem. 2000 Jul 21;275(29):22373–22380
  27. Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, et al. beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis. J. Biol. Chem. 2001 Nov 9;276(45):42509–42513
  28. Lin FT, Krueger KM, Kendall HE, Daaka Y, Fredericks ZL, Pitcher JA, et al. Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. J. Biol. Chem. 1997 Dec 5;272(49):31051–31057
  29. Kim YM, Barak LS, Caron MG, Benovic JL. Regulation of arrestin-3 phosphorylation by casein kinase II. J. Biol. Chem. 2002 May 10;277(19):16837–16846
  30. Zhang X, Wang F, Chen X, Li J, Xiang B, Zhang YQ, et al. Beta-arrestin1 and beta-arrestin2 are differentially required for phosphorylation-dependent and -independent internalization of delta-opioid receptors. J. Neurochem. 2005 Oct;95(1):169–178
  31. Kumar P, Lau CS, Mathur M, Wang P, DeFea KA. Differential effects of beta-arrestins on the internalization, desensitization and ERK1/2 activation downstream of protease activated receptor-2. Am. J. Physiol. Cell Physiol. 2007 Jul;293(1):C346–C357
  32. Frenzel R, Voigt C, Paschke R. The human thyrotropin receptor is predominantly internalized by beta-arrestin 2. Endocrinology. 2006 Jun;147(6):3114–3122
  33. Naga Prasad SV, Laporte SA, Chamberlain D, Caron MG, Barak L, Rockman HA. Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex. J Cell Biol. 2002 Aug 5;158(3):563–575
  34. Perrino C, Schroder JN, Lima B, Villamizar N, Nienaber JJ, Milano CA, et al. Dynamic regulation of phosphoinositide 3-kinase-gamma activity and beta-adrenergic receptor trafficking in end-stage human heart failure. Circulation. 2007 Nov 27;116(22):2571–2579
  35. Perrino C, Naga Prasad SV, Schroder JN, Hata JA, Milano C, Rockman HA. Restoration of beta-adrenergic receptor signaling and contractile function in heart failure by disruption of the betaARK1/phosphoinositide 3-kinase complex. Circulation. 2005 May 24;111(20):2579–2587
  36. Nienaber JJ, Tachibana H, Naga Prasad SV, Esposito G, Wu D, Mao L, et al. Inhibition of receptor-localized PI3K preserves cardiac beta-adrenergic receptor function and ameliorates pressure overload heart failure. J. Clin. Invest. 2003 Oct;112(7):1067–1079
  37. Oakley RH, Laporte SA, Holt JA, Caron MG, Barak LS. Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J. Biol. Chem. 2000 Jun 2;275(22):17201–17210
  38. Mundell SJ, Matharu AL, Kelly E, Benovic JL. Arrestin isoforms dictate differential kinetics of A2B adenosine receptor trafficking. Biochemistry. 2000 Oct 24;39(42):12828–12836
  39. Vines CM, Revankar CM, Maestas DC, LaRusch LL, Cimino DF, Kohout TA, et al. N-formyl peptide receptors internalize but do not recycle in the absence of arrestins. J. Biol. Chem. 2003 Oct 24;278(43):41581–41584
  40. Rapacciuolo A, Suvarna S, Barki-Harrington L, Luttrell LM, Cong M, Lefkowitz RJ, et al. Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways. J. Biol. Chem. 2003 Sep 12;278(37):35403–35411
  41. Marchese A, Benovic JL. Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J. Biol. Chem. 2001 Dec 7;276(49):45509–45512
  42. Jacob C, Cottrell GS, Gehringer D, Schmidlin F, Grady EF, Bunnett NW. c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2. J. Biol. Chem. 2005 Apr 22;280(16):16076–16087
  43. Cottrell GS, Padilla B, Pikios S, Roosterman D, Steinhoff M, Gehringer D, et al. Ubiquitin-dependent down-regulation of the neurokinin-1 receptor. J. Biol. Chem. 2006 Sep 22;281(38):27773–27783
  44. Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science. 2001 Nov 9;294(5545):1307–1313
  45. Shenoy SK, Barak LS, Xiao K, Ahn S, Berthouze M, Shukla AK, et al. Ubiquitination of beta -arrestin links 7-transmembrane receptor endocytosis and ERK activation. J. Biol. Chem. 2007 Jul 31;
  46. Girnita L, Shenoy SK, Sehat B, Vasilcanu R, Girnita A, Lefkowitz RJ, et al. {beta}-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. 2005 Jul 1;280(26):24412–24419
  47. Wang Y, Tang Y, Teng L, Wu Y, Zhao X, Pei G. Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. Nat. Immunol. 2006 Feb;7(2):139–147
  48. Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, et al. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science. 2003 Sep 5;301(5638):1394–1397
  49. Wu JH, Peppel K, Nelson CD, Lin FT, Kohout TA, Miller WE, et al. The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor. J. Biol. Chem. 2003 Nov 7;278(45):44238–44245
  50. Bhattacharya M, Anborgh PH, Babwah AV, Dale LB, Dobransky T, Benovic JL, et al. Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization. Nat. Cell Biol. 2002 Aug;4(8):547–555
  51. Barnes WG, Reiter E, Violin JD, Ren XR, Milligan G, Lefkowitz RJ. beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. J. Biol. Chem. 2005 Mar 4;280(9):8041–8050
  52. Imamura T, Huang J, Dalle S, Ugi S, Usui I, Luttrell LM, et al. beta -Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport. J. Biol. Chem. 2001 Nov 23;276(47):43663–43667
  53. DeFea KA, Zalevsky J, Thoma MS, Dery O, Mullins RD, Bunnett NW. beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol. 2000 Mar 20;148(6):1267–1281
  54. McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME, Lin FT, et al. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science. 2000 Nov 24;290(5496):1574–1577
  55. Tohgo A, Choy EW, Gesty-Palmer D, Pierce KL, Laporte S, Oakley RH, et al. The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation. J. Biol. Chem. 2003 Feb 21;278(8):6258–6267
  56. Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, et al. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science. 1999 Jan 29;283(5402):655–661
  57. Barlic J, Andrews JD, Kelvin AA, Bosinger SE, DeVries ME, Xu L, et al. Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI. Nat. Immunol. 2000 Sep;1(3):227–233
  58. McKay MM, Morrison DK. Integrating signals from RTKs to ERK/MAPK. Oncogene. 2007 May 14;26(22):3113–3121
  59. Jarpe MB, Widmann C, Knall C, Schlesinger TK, Gibson S, Yujiri T, et al. Anti-apoptotic versus pro-apoptotic signal transduction: checkpoints and stop signs along the road to death. Oncogene. 1998 Sep 17;17(11 Reviews):1475–1482
  60. Ahn S, Shenoy SK, Wei H, Lefkowitz RJ. Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor. J. Biol. Chem. 2004 Aug 20;279(34):35518–35525
  61. Tohgo A, Pierce KL, Choy EW, Lefkowitz RJ, Luttrell LM. beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J. Biol. Chem. 2002 Mar 15;277(11):9429–9436
  62. Wei H, Ahn S, Barnes WG, Lefkowitz RJ. Stable interaction between beta-arrestin 2 and angiotensin type 1A receptor is required for beta-arrestin 2-mediated activation of extracellular signal-regulated kinases 1 and 2. J. Biol. Chem. 2004 Nov 12;279(46):48255–48261
  63. Aplin M, Christensen GL, Schneider M, Heydorn A, Gammeltoft S, Kjolbye AL, et al. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes. Basic Clin. Pharmacol. Toxicol. 2007 May;100(5):296–301
  64. Zhai P, Yamamoto M, Galeotti J, Liu J, Masurekar M, Thaisz J, et al. Cardiac-specific overexpression of AT1 receptor mutant lacking G alpha q/G alpha i coupling causes hypertrophy and bradycardia in transgenic mice. J. Clin. Invest. 2005 Nov;115(11):3045–3056
  65. Ahn S, Wei H, Garrison TR, Lefkowitz RJ. Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2. J. Biol. Chem. 2004 Feb 27;279(9):7807–7811
  66. Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L, Luttrell LM, et al. 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. U. S. A. 2003 Sep 16;100(19):10782–10787
  67. Kuo FT, Lu TL, Fu HW. Opposing effects of beta-arrestin1 and beta-arrestin2 on activation and degradation of Src induced by protease-activated receptor 1. Cell Signal. 2006 Nov;18(11):1914–1923
  68. Sneddon WB, Friedman PA. Beta-arrestin-dependent parathyroid hormone-stimulated extracellular signal-regulated kinase activation and parathyroid hormone type 1 receptor internalization. Endocrinology. 2007 Aug;148(8):4073–4079
  69. Fan H, Luttrell LM, Tempel GE, Senn JJ, Halushka PV, Cook JA. Beta-arrestins 1 and 2 differentially regulate LPS-induced signaling and pro-inflammatory gene expression. Mol. Immunol. 2007 May;44(12):3092–3099
  70. Miller WE, Maudsley S, Ahn S, Khan KD, Luttrell LM, Lefkowitz RJ. 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. 2000 Apr 14;275(15):11312–11319
  71. DeFea KA, Vaughn ZD, O'Bryan EM, Nishijima D, Dery O, Bunnett NW. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta -arrestin-dependent scaffolding complex. Proc. Natl. Acad. Sci. U. S. A. 2000 Sep 26;97(20):11086–11091
  72. Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, Pierce KL, et al. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc. Natl. Acad. Sci. U. S. A. 2001 Feb 27;98(5):2449–2454
  73. Miller WE, McDonald PH, Cai SF, Field ME, Davis RJ, Lefkowitz RJ. Identification of a motif in the carboxyl terminus of beta -arrestin2 responsible for activation of JNK3. J. Biol. Chem. 2001 Jul 27;276(30):27770–27777
  74. Sun Y, Cheng Z, Ma L, Pei G. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J. Biol. Chem. 2002 Dec 20;277(51):49212–49219
  75. Miller WE, Houtz DA, Nelson CD, Kolattukudy PE, Lefkowitz RJ. 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. 2003 Jun 13;278(24):21663–21671
  76. Bruchas MR, Macey TA, Lowe JD, Chavkin C. Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. J. Biol. Chem. 2006 Jun 30;281(26):18081–18089
  77. Povsic TJ, Kohout TA, Lefkowitz RJ. Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis. J. Biol. Chem. 2003 Dec 19;278(51):51334–51339
  78. Goel R, Phillips-Mason PJ, Raben DM, Baldassare JJ. alpha-Thrombin induces rapid and sustained Akt phosphorylation by beta-arrestin1-dependent and -independent mechanisms, and only the sustained Akt phosphorylation is essential for G1 phase progression. J. Biol. Chem. 2002 May 24;277(21):18640–18648
  79. Dasgupta P, Rastogi S, Pillai S, Ordonez-Ercan D, Morris M, Haura E, et al. Nicotine induces cell proliferation by beta-arrestin-mediated activation of Src and Rb-Raf-1 pathways. J. Clin. Invest. 2006 Aug;116(8):2208–2217
  80. Shenoy SK, Drake MT, Nelson CD, Houtz DA, Xiao K, Madabushi S, et al. beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor. J. Biol. Chem. 2006 Jan 13;281(2):1261–1273
  81. Aplin M, Christensen GL, Schneider M, Heydorn A, Gammeltoft S, Kjolbye AL, et al. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts. Basic Clin. Pharmacol. Toxicol. 2007 May;100(5):289–295
  82. Charest PG, Oligny-Longpre G, Bonin H, Azzi M, Bouvier M. The V2 vasopressin receptor stimulates ERK1/2 activity independently of heterotrimeric G protein signalling. Cell Signal. 2007 Jan;19(1):32–41
  83. Gesty-Palmer D, Chen M, Reiter E, Ahn S, Nelson CD, Wang S, et al. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J. Biol. Chem. 2006 Apr 21;281(16):10856–10864
  84. Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, et al. beta-Arrestin-mediated beta(1)-adrenergic receptor transactivation of the EGFR confers cardioprotection. J. Clin. Invest. 2007 Sep;117(9):2445–2458
  85. Brodde OE, Michel MC. Adrenergic and muscarinic receptors in the human heart. Pharmacol. Rev. 1999 Dec;51(4):651–690
  86. Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmembrane-spanning receptors and heart function. Nature. 2002 Jan 10;415(6868):206–212
  87. Xiang Y, Kobilka BK. Myocyte adrenoceptor signaling pathways. Science. 2003 Jun 6;300(5625):1530–1532
  88. Ungerer M, Bohm M, Elce JS, Erdmann E, Lohse MJ. Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart. Circulation. 1993 Feb;87(2):454–463
  89. Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C, et al. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature. 1999 Dec 23–30;402(6764):884–888
  90. Shah BH, Catt KJ. Matrix metalloproteinase-dependent EGF receptor activation in hypertension and left ventricular hypertrophy. Trends Endocrinol. Metab. 2004 Aug;15(6):241–243
  91. Rajagopal K, Whalen EJ, Violin JD, Stiber JA, Rosenberg PB, Premont RT, et al. Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes. Proc. Natl. Acad. Sci. U. S. A. 2006 Oct 31;103(44):16284–16289
  92. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999 Jan 2; 353(9146): 9–13.
  93. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999 Jun 12; 353(9169): 2001–7.
  94. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N. Engl. J. Med. 1996 May 23;334(21):1349–1355
  95. Barki-Harrington L, Luttrell LM, Rockman HA. Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor-receptor interaction in vivo. Circulation. 2003 Sep 30;108(13):1611–1618
  96. Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, et al. Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14555–14560
  97. Wisler JW, Dewire SM, Whalen EJ, Violin JD, Drake MT, Ahn S, et al. A unique mechanism of beta-blocker action: Carvedilol stimulates beta-arrestin signaling. Proc. Natl. Acad. Sci. U. S. A. 2007 Oct 16;104(42):16657–16662
  98. Azzi M, Charest PG, Angers S, Rousseau G, Kohout T, Bouvier M, et al. Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc. Natl. Acad. Sci. U. S. A. 2003 Sep 30;100(20):11406–11411
  99. Percherancier Y, Berchiche YA, Slight I, Volkmer-Engert R, Tamamura H, Fujii N, et al. Bioluminescence resonance energy transfer reveals ligand-induced conformational changes in CXCR4 homo- and heterodimers. J. Biol. Chem. 2005 Mar 18;280(11):9895–9903
  100. Shukla AK, Violin JD, Whalen EJ, Gesty-Palmer D, Shenoy SK, Lefkowitz RJ. Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptors. Proc. Natl. Acad. Sci. U. S. A. 2008 Jul 22;105(29):9988–9993
  101. Lefkowitz RJ, Whalen EJ. beta-arrestins: traffic cops of cell signaling. Curr. Opin. Cell Biol. 2004 Apr;16(2):162–168
  102. Xiao K, McClatchy DB, Shukla AK, Zhao Y, Chen M, Shenoy SK, et al. Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proc. Natl. Acad. Sci. U. S. A. 2007 Jul 17;104(29):12011–12016

PII: S0022-2828(08)01408-9

doi: 10.1016/j.yjmcc.2008.11.015

Journal of Molecular and Cellular Cardiology
Volume 46, Issue 3 , Pages 300-308 , March 2009