Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Multifaceted role of β-arrestins in inflammation and disease

Genes & Immunity volume 16, pages 499–513 (2015)Cite this article

Subjects

An Erratum to this article was published on 03 December 2015

This article has been updated

Abstract

Arrestins are intracellular scaffolding proteins known to regulate a range of biochemical processes including G protein-coupled receptor (GPCR) desensitization, signal attenuation, receptor turnover and downstream signaling cascades. Their roles in regulation of signaling network have lately been extended to receptors outside of the GPCR family, demonstrating their roles as important scaffolding proteins in various physiological processes including proliferation, differentiation and apoptosis. Recent studies have demonstrated a critical role for arrestins in immunological processes including key functions in inflammatory signaling pathways. In this review, we provide a comprehensive analysis of the different functions of the arrestin family of proteins especially related to immunity and inflammatory diseases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

Change history

  • 03 December 2015

    This article has been corrected since Advance Online Publication and an erratum is also printed in this issue.

References

  1. Craft CM, Whitmore DH . The arrestin superfamily: cone arrestins are a fourth family. FEBS Lett 1995; 362: 247–255.

    CAS  PubMed  Google Scholar 

  2. DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK . Beta-arrestins and cell signaling. Annu Rev Physiol 2007; 69: 483–510.

    CAS  PubMed  Google Scholar 

  3. Lohse M, Benovic J, Codina J, Caron M, Lefkowitz R . beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 1990; 248: 1547–1550.

    CAS  PubMed  Google Scholar 

  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 USA 1987; 84: 8879–8882.

    CAS  PubMed  Google Scholar 

  5. Pitcher J, Lohse MJ, Codina J, Caron MG, Lefkowitz RJ . Desensitization of the isolated beta 2-adrenergic receptor by beta-adrenergic receptor kinase, cAMP-dependent protein kinase, and protein kinase C occurs via distinct molecular mechanisms. Biochemistry 1992; 31: 3193–3197.

    CAS  PubMed  Google Scholar 

  6. Sibley DR, Benovic JL, Caron MG, Lefkowitz RJ . Regulation of transmembrane signaling by receptor phosphorylation. Cell 1987; 48: 913–922.

    CAS  PubMed  Google Scholar 

  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; 267: 8558–8564.

    CAS  PubMed  Google Scholar 

  8. Wang P, Wu Y, Ge X, Ma L, Pei G . Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus. J Biol Chem 2003; 278: 11648–11653.

    CAS  PubMed  Google Scholar 

  9. Milano SK, Kim YM, Stefano FP, Benovic JL, Brenner C . Nonvisual arrestin oligomerization and cellular localization are regulated by inositol hexakisphosphate binding. J Biol Chem 2006; 281: 9812–9823.

    CAS  PubMed  Google Scholar 

  10. Zhang M, Liu X, Zhang Y, Zhao J . Loss of betaarrestin1 and betaarrestin2 contributes to pulmonary hypoplasia and neonatal lethality in mice. Dev Biol 2010; 339: 407–417.

    CAS  PubMed  Google Scholar 

  11. Conner DA, Mathier MA, Mortensen RM, Christe M, Vatner SF, Seidman CE et al. β-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to β-adrenergic stimulation. Circ Res 1997; 81: 1021–1026.

    CAS  PubMed  Google Scholar 

  12. Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin F-T . Enhanced morphine analgesia in mice lacking β-arrestin 2. Science 1999; 286: 2495–2498.

    CAS  PubMed  Google Scholar 

  13. Ferrari SL, Pierroz DD, Glatt V, Goddard DS, Bianchi EN, Lin FT et al. Bone response to intermittent parathyroid hormone is altered in mice null for {beta}-Arrestin2. Endocrinology 2005; 146: 1854–1862.

    CAS  PubMed  Google Scholar 

  14. Goodman OB Jr, 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; 383: 447–450.

    CAS  PubMed  Google Scholar 

  15. Goodman OB Jr, Krupnick JG, Gurevich VV, Benovic JL, Keen JH . Arrestin/clathrin interaction. Localization of the arrestin binding locus to the clathrin terminal domain. J Biol Chem 1997; 272: 15017–15022.

    CAS  PubMed  Google Scholar 

  16. Krupnick JG, Goodman OB Jr, Keen JH, Benovic JL . Arrestin/clathrin interaction. Localization of the clathrin binding domain of nonvisual arrestins to the carboxy terminus. J Biol Chem 1997; 272: 15011–15016.

    CAS  PubMed  Google Scholar 

  17. 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; 272: 31051–31057.

    CAS  PubMed  Google Scholar 

  18. Luttrell L, Ferguson S, Daaka Y, Miller W, Maudsley S, Della Rocca G et al. β-Arrestin-dependent formation of β2 adrenergic receptor-Src protein kinase complexes. Science 1999; 283: 655–661.

    CAS  PubMed  Google Scholar 

  19. Lin FT, Chen W, Shenoy S, Cong M, Exum ST, Lefkowitz RJ . Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors. Biochemistry 2002; 41: 10692–10699.

    CAS  PubMed  Google Scholar 

  20. Kim YM, Barak LS, Caron MG, Benovic JL . Regulation of arrestin-3 phosphorylation by casein kinase II. J Biol Chem 2002; 277: 16837–16846.

    CAS  PubMed  Google Scholar 

  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 USA 1999; 96: 3712–3717.

    CAS  PubMed  Google Scholar 

  22. Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG . The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits. J Biol Chem 2000; 275: 23120–23126.

    CAS  PubMed  Google Scholar 

  23. McDonald PH, Cote NL, Lin FT, Premont RT, Pitcher JA, Lefkowitz RJ . Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. J Biol Chem 1999; 274: 10677–10680.

    CAS  PubMed  Google Scholar 

  24. Song X, Raman D, Gurevich EV, Vishnivetskiy SA, Gurevich VV . Visual and both non-visual arrestins in their ‘inactive’ conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm. J Biol Chem 2006; 281: 21491–21499.

    CAS  PubMed  Google Scholar 

  25. Song X, Gurevich EV, Gurevich VV . Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sites. J Neurochem 2007; 103: 1053–1062.

    CAS  PubMed  Google Scholar 

  26. McDonald PH, Chow C-W, Miller WE, Laporte SA, Field ME, Lin F-T et al. β-Arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 2000; 290: 1574–1577.

    CAS  Google Scholar 

  27. 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; 276: 27770–27777.

    CAS  PubMed  Google Scholar 

  28. Scott MG, Le Rouzic E, Perianin A, Pierotti V, Enslen H, Benichou S et al. Differential nucleocytoplasmic shuttling of beta-arrestins. Characterization of a leucine-rich nuclear export signal in beta-arrestin2. J Biol Chem 2002; 277: 37693–37701.

    CAS  PubMed  Google Scholar 

  29. Zhan X, Kaoud TS, Kook S, Dalby KN, Gurevich VV . JNK3 enzyme binding to Arrestin-3 differentially affects the recruitment of upstream mitogen-activated protein (MAP) kinase kinases. J Biol Chem 2013; 288: 28535–28547.

    CAS  PubMed  Google Scholar 

  30. Li X, MacLeod R, Dunlop AJ, Edwards HV, Advant N, Gibson LC et al. A scanning peptide array approach uncovers association sites within the JNK/beta arrestin signalling complex. FEBS Lett 2009; 583: 3310–3316.

    CAS  PubMed  Google Scholar 

  31. Zhan X, Kook S, Gurevich EV, Gurevich VV . Arrestin-dependent activation of JNK family kinases. Handb Exp Pharmacol 2014; 219: 259–280.

    CAS  PubMed  Google Scholar 

  32. Farooq A, Hoque R, Ouyang X, Farooq A, Ghani A, Ahsan K et al. Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a beta-arrestin-2 pathway. Am J Physiol Gastrointest Liver Physiol 2014; 307: G732–G740.

    CAS  PubMed  Google Scholar 

  33. Luttrell LM, Miller WE . Arrestins as regulators of kinases and phosphatases. Prog Mol Biol Transl Sci 2013; 118: 115–147.

    CAS  PubMed  Google Scholar 

  34. DeFea KA, Zalevsky J, Thoma MS, Dery O, Mullins RD, Bunnett NW . β-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol 2000; 148: 1267–1281.

    CAS  PubMed  Google Scholar 

  35. 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 USA 2001; 98: 2449–2454.

    CAS  PubMed  Google Scholar 

  36. 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; 277: 9429–9436.

    CAS  PubMed  Google Scholar 

  37. 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 β-arrestin-dependent scaffolding complex. Proc Natl Acad Sci USA 2000; 97: 11086–11091.

    CAS  PubMed  Google Scholar 

  38. 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; 278: 6258–6267.

    CAS  PubMed  Google Scholar 

  39. DeFea KA . β-arrestins as regulators of signal termination and transduction: how do they determine what to scaffold? Cell Signal 2011; 23: 621–629.

    CAS  PubMed  Google Scholar 

  40. Bourquard T, Landomiel F, Reiter E, Crepieux P, Ritchie DW, Aze J et al. Unraveling the molecular architecture of a G protein-coupled receptor/beta-arrestin/Erk module complex. Sci Rep 2015; 5: 10760.

    CAS  PubMed  Google Scholar 

  41. Gong K, Li Z, Xu M, Du J, Lv Z, Zhang Y . A novel protein kinase A-independent, beta-arrestin-1-dependent signaling pathway for p38 mitogen-activated protein kinase activation by beta2-adrenergic receptors. J Biol Chem 2008; 283: 29028–29036.

    CAS  PubMed  Google Scholar 

  42. Sun Y, Cheng Z, Ma L, Pei G . β-Arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem 2002; 277: 49212–49219.

    CAS  PubMed  Google Scholar 

  43. 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; 281: 18081–18089.

    CAS  PubMed  Google Scholar 

  44. 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; 278: 21663–21671.

    CAS  PubMed  Google Scholar 

  45. Witherow DS, Garrison TR, Miller WE, Lefkowitz RJ . beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proc Natl Acad Sci USA 2004; 101: 8603–8607.

    CAS  PubMed  Google Scholar 

  46. Gao H, Sun Y, Wu Y, Luan B, Wang Y, Qu B et al. Identification of β-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways. Mol Cell 2004; 14: 303–317.

    CAS  PubMed  Google Scholar 

  47. Luan B, Zhang Z, Wu Y, Kang J, Pei G . Beta-arrestin2 functions as a phosphorylation-regulated suppressor of UV-induced NF-kappaB activation. EMBO j 2005; 24: 4237–4246.

    CAS  PubMed  Google Scholar 

  48. Sun J, Lin X . Beta-arrestin 2 is required for lysophosphatidic acid-induced NF-kappaB activation. Proc Natl Acad Sci USA 2008; 105: 17085–17090.

    CAS  PubMed  Google Scholar 

  49. Cianfrocca R, Tocci P, Semprucci E, Spinella F, Di Castro V, Bagnato A et al. β-Arrestin 1 is required for endothelin-1-induced NF-κB activation in ovarian cancer cells. Life Sciences 2014; 118: 179–184.

    CAS  PubMed  Google Scholar 

  50. Kang J, Shi Y, Xiang B, Qu B, Su W, Zhu M et al. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell 2005; 123: 833–847.

    CAS  PubMed  Google Scholar 

  51. Shi Y, Feng Y, Kang J, Liu C, Li Z, Li D et al. Critical regulation of CD4+ T cell survival and autoimmunity by beta-arrestin 1. Nat Immunol 2007; 8: 817–824.

    CAS  PubMed  Google Scholar 

  52. Hu Z, Huang Y, Liu Y, Sun Y, Zhou Y, Gu M et al. β-Arrestin 1 modulates functions of autoimmune T cells from primary biliary cirrhosis patients. J Clin Immunol 2011; 31: 346–355.

    CAS  PubMed  Google Scholar 

  53. 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; 294: 1307–1313.

    CAS  PubMed  Google Scholar 

  54. Wang P, Gao H, Ni Y, Wang B, Wu Y, Ji L et al. Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2. J Biol Chem 2003; 278: 6363–6370.

    CAS  PubMed  Google Scholar 

  55. Zoudilova M, Min J, Richards HL, Carter D, Huang T, DeFea KA . β-Arrestins scaffold cofilin with chronophin to direct localized actin filament severing and membrane protrusions downstream of protease-activated receptor-2. J Biol Chem 2010; 285: 14318–14329.

    CAS  PubMed  Google Scholar 

  56. Sharma D, Malik A, Lee E, Britton RA, Parameswaran N . Gene dosage-dependent negative regulatory role of β-Arrestin-2 in polymicrobial infection-induced inflammation. Infect Immun 2013; 81: 3035–3044.

    CAS  PubMed  Google Scholar 

  57. Sharma D, Packiriswamy N, Malik A, Lucas PC, Parameswaran N . Nonhematopoietic beta-Arrestin-1 inhibits inflammation in a murine model of polymicrobial sepsis. Am J Pathol 2014; 184: 2297–2309.

    CAS  PubMed  Google Scholar 

  58. Lattin JE, Greenwood KP, Daly NL, Kelly G, Zidar DA, Clark RJ et al. Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival. Mol Immunol 2009; 47: 340–347.

    CAS  PubMed  Google Scholar 

  59. Aragay AM, Mellado M, Frade JMR, Martin AM, Jimenez-Sainz MC, Martinez-A C et al. Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2. Proc Natl Acad Sci USA 1998; 95: 2985–2990.

    CAS  PubMed  Google Scholar 

  60. Richardson RM, Marjoram RJ, Barak LS, Snyderman R . Role of the cytoplasmic tails of CXCR1 and CXCR2 in mediating leukocyte migration, activation, and regulation. J Immunol 2003; 170: 2904–2911.

    CAS  PubMed  Google Scholar 

  61. Fan GH, Yang W, Wang XJ, Qian Q, Richmond A . Identification of a motif in the carboxyl terminus of CXCR2 that is involved in adaptin 2 binding and receptor internalization. Biochemistry 2001; 40: 791–800.

    CAS  PubMed  Google Scholar 

  62. Orsini MJ, Parent JL, Mundell SJ, Marchese A, Benovic JL . Trafficking of the HIV coreceptor CXCR4. Role of arrestins and identification of residues in the c-terminal tail that mediate receptor internalization. J Biol Chem 1999; 274: 31076–31086.

    CAS  PubMed  Google Scholar 

  63. Cheng ZJ, Zhao J, Sun Y, Hu W, Wu YL, Cen B et al. β-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4. J Biol Chem 2000; 275: 2479–2485.

    CAS  PubMed  Google Scholar 

  64. Décaillot FM, Kazmi MA, Lin Y, Ray-Saha S, Sakmar TP, Sachdev P . CXCR7/CXCR4 heterodimer constitutively recruits β-Arrestin to enhance cell migration. J Biol Chem 2011; 286: 32188–32197.

    PubMed  Google Scholar 

  65. Su Y, Raghuwanshi SK, Yu Y, Nanney LB, Richardson RM, Richmond A . Altered CXCR2 signaling in beta-arrestin-2-deficient mouse models. J Immunol 2005; 175: 5396–5402.

    CAS  PubMed  Google Scholar 

  66. Basher F, Fan H, Zingarelli B, Borg KT, Luttrell LM, Tempel GE et al. β-Arrestin 2: a negative regulator of inflammatory responses in polymorphonuclear leukocytes. Int J Clin Exp Med 2008; 1: 32–41.

    CAS  PubMed  Google Scholar 

  67. Gaffal E, Jakobs M, Glodde N, Schroder R, Kostenis E, Tuting T . beta-arrestin 2 inhibits proinflammatory chemokine production and attenuates contact allergic inflammation in the skin. J Invest Dermatol 2014; 134: 2131–2137.

    CAS  PubMed  Google Scholar 

  68. 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; 1: 227–233.

    CAS  PubMed  Google Scholar 

  69. Fong AM, Premont RT, Richardson RM, Yu Y-RA, Lefkowitz RJ, Patel DD . Defective lymphocyte chemotaxis in β-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci USA 2002; 99: 7478–7483.

    CAS  PubMed  Google Scholar 

  70. Walker JKL, Fong AM, Lawson BL, Savov JD, Patel DD, Schwartz DA et al. β-Arrestin-2 regulates the development of allergic asthma. J Clin Invest 2003; 112: 566–574.

    CAS  PubMed  Google Scholar 

  71. Cheung R, Malik M, Ravyn V, Tomkowicz B, Ptasznik A, Collman RG . An arrestin-dependent multi-kinase signaling complex mediates MIP-1β/CCL4 signaling and chemotaxis of primary human macrophages. J Leukoc Biol 2009; 86: 833–845.

    CAS  PubMed  Google Scholar 

  72. Ge L, Shenoy SK, Lefkowitz RJ, DeFea K . Constitutive protease-activated receptor-2-mediated migration of MDA MB-231 breast cancer cells requires both beta-arrestin-1 and -2. J Biol Chem 2004; 279: 55419–55424.

    CAS  PubMed  Google Scholar 

  73. Ahamed J, Haribabu B, Ali H . Cutting edge: differential regulation of chemoattractant receptor-induced degranulation and chemokine production by receptor phosphorylation. J Immunol 2001; 167: 3559–3563.

    CAS  PubMed  Google Scholar 

  74. Vibhuti A, Gupta K, Subramanian H, Guo Q, Ali H . Distinct and shared roles of beta-arrestin-1 and beta-arrestin-2 on the regulation of C3a receptor signaling in human mast cells. PLoS One 2011; 6: e19585.

    CAS  PubMed  Google Scholar 

  75. Bamberg CE, Mackay CR, Lee H, Zahra D, Jackson J, Lim YS et al. The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. J Biol Chem 2010; 285: 7633–7644.

    CAS  PubMed  Google Scholar 

  76. Bohm SK, Khitin LM, Grady EF, Aponte G, Payan DG, Bunnett NW . Mechanisms of desensitization and resensitization of proteinase-activated receptor-2. J Biol Chem 1996; 271: 22003–22016.

    CAS  PubMed  Google Scholar 

  77. Jacob C, Yang P-C, Darmoul D, Amadesi S, Saito T, Cottrell GS et al. Mast cell tryptase controls paracellular permeability of the intestine: role of protease-activated receptor 2 and β-arrestins. J Biol Chem 2005; 280: 31936–31948.

    CAS  PubMed  Google Scholar 

  78. Loniewski K, Shi Y, Pestka J, Parameswaran N . Toll-like receptors differentially regulate GPCR kinases and arrestins in primary macrophages. Mol Immunol 2008; 45: 2312–2322.

    CAS  PubMed  Google Scholar 

  79. Kizaki T, Izawa T, Sakurai T, Haga S, Taniguchi N, Tajiri H et al. Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear factor-kappaB activation through beta-arrestin 2. Immunology 2008; 124: 348–356.

    CAS  PubMed  Google Scholar 

  80. Kizaki T, Shirato K, Sakurai T, Ogasawara JE, Oh-ishi S, Matsuoka T et al. Beta2-adrenergic receptor regulate Toll-like receptor 4-induced late-phase NF-kappaB activation. Mol Immunol 2009; 46: 1195–1203.

    CAS  PubMed  Google Scholar 

  81. Wang W, Xu M, Zhang YY, He B . Fenoterol, a beta(2)-adrenoceptor agonist, inhibits LPS-induced membrane-bound CD14, TLR4/CD14 complex, and inflammatory cytokines production through beta-arrestin-2 in THP-1 cell line. Acta Pharmacol Sin 2009; 30: 1522–1528.

    CAS  PubMed  Google Scholar 

  82. Wang W, Zhang Y, Xu M, Zhang YY, He B . Fenoterol inhibits LPS-induced AMPK activation and inflammatory cytokine production through beta-arrestin-2 in THP-1 cell line. Biochem Biophys Res Commun 2015; 462: 119–123.

    PubMed  Google Scholar 

  83. Parameswaran N, Pao CS, Leonhard KS, Kang DS, Kratz M, Ley SC et al. Arrestin-2 and G protein-coupled receptor kinase 5 interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages. J Biol Chem 2006; 281: 34159–34170.

    CAS  PubMed  Google Scholar 

  84. Fan H, Luttrell LM, Tempel GE, Senn JJ, Halushka PV, Cook JA . β-arrestins 1 and 2 differentially regulate LPS-induced signaling and pro-inflammatory gene expression. Mol Immunol 2007; 44: 3092–3099.

    CAS  PubMed  Google Scholar 

  85. 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; 7: 139–147.

    CAS  PubMed  Google Scholar 

  86. Fan H, Bitto A, Zingarelli B, Luttrell LM, Borg K, Halushka PV et al. β-arrestin 2 negatively regulates sepsis-induced inflammation. Immunology 2010; 130: 344–351.

    CAS  PubMed  Google Scholar 

  87. Li H, Sun X, LeSage G, Zhang Y, Liang Z, Chen J et al. beta-arrestin 2 regulates Toll-like receptor 4-mediated apoptotic signalling through glycogen synthase kinase-3beta. Immunology 2010; 130: 556–563.

    CAS  PubMed  Google Scholar 

  88. Xiao N, Li H, Mei W, Cheng J . SUMOylation attenuates human beta-arrestin 2 inhibition of IL-1R/TRAF6 signaling. J Biol Chem 2015; 290: 1927–1935.

    CAS  PubMed  Google Scholar 

  89. Seregin SS, Appledorn DM, Patial S, Bujold M, Nance W, Godbehere S et al. beta-Arrestins modulate Adenovirus-vector-induced innate immune responses: differential regulation by beta-arrestin-1 and beta-arrestin-2. Virus Res 2010; 147: 123–134.

    CAS  PubMed  Google Scholar 

  90. Appledorn DM, Patial S, Godbehere S, Parameswaran N, Amalfitano A . TRIF, and TRIF-interacting TLRs differentially modulate several adenovirus vector-induced immune responses. J Innate Immun 2009; 1: 376–388.

    CAS  PubMed  Google Scholar 

  91. Appledorn DM, Patial S, McBride A, Godbehere S, Van Rooijen N, Parameswaran N et al. Adenovirus vector-induced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo. J Immunol 2008; 181: 2134–2144.

    CAS  Google Scholar 

  92. Kawamata Y, Imamura T, Babendure JL, Lu JC, Yoshizaki T, Olefsky JM . Tumor necrosis factor receptor-1 can function through a G alpha q/11-beta-arrestin-1 signaling complex. J Biol Chem 2007; 282: 28549–28556.

    CAS  PubMed  Google Scholar 

  93. Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP et al. β-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science 2003; 301: 1394–1397.

    CAS  PubMed  Google Scholar 

  94. Mythreye K, Blobe GC . The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42. Proc Natl Acad Sci USA 2009; 106: 8221–8226.

    CAS  PubMed  Google Scholar 

  95. Zhang Y, Liu C, Wei B, Pei G . Loss of beta-arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells. Immunology 2013; 140: 430–440.

    CAS  PubMed  Google Scholar 

  96. Mo W, Zhang L, Yang G, Zhai J, Hu Z, Chen Y et al. Nuclear beta-arrestin1 functions as a scaffold for the dephosphorylation of STAT1 and moderates the antiviral activity of IFN-gamma. Mol Cell 2008; 31: 695–707.

    CAS  PubMed  Google Scholar 

  97. Heim MH, Moradpour D, Blum HE . Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway. J Virol 1999; 73: 8469–8475.

    CAS  PubMed  Google Scholar 

  98. Yang PL, Althage A, Chung J, Chisari FV . Hydrodynamic injection of viral DNA: a mouse model of acute hepatitis B virus infection. Proc Natl Acad Sci USA 2002; 99: 13825–13830.

    CAS  PubMed  Google Scholar 

  99. Bari R, Bell T, Leung WH, Vong QP, Chan WK, Das Gupta N et al. Significant functional heterogeneity among KIR2DL1 alleles and a pivotal role of arginine 245. Blood 2009; 114: 5182–5190.

    CAS  PubMed  Google Scholar 

  100. Yu MC, Su LL, Zou L, Liu Y, Wu N, Kong L et al. An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells. Nat Immunol 2008; 9: 898–907.

    CAS  PubMed  Google Scholar 

  101. Li M, Xia P, Du Y, Liu S, Huang G, Chen J et al. T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus receptor (PVR) ligand engagement suppresses interferon-gamma production of natural killer cells via beta-arrestin 2-mediated negative signaling. J Biol Chem 2014; 289: 17647–17657.

    CAS  PubMed  Google Scholar 

  102. Bjorgo E, Solheim SA, Abrahamsen H, Baillie GS, Brown KM, Berge T et al. Cross talk between phosphatidylinositol 3-kinase and cyclic AMP (cAMP)-protein kinase a signaling pathways at the level of a protein kinase B/beta-arrestin/cAMP phosphodiesterase 4 complex. Mol Cell Biol 2010; 30: 1660–1672.

    PubMed  Google Scholar 

  103. Zhang Y, Liu C, Wei B, Pei G . Loss of β-arrestin 2 exacerbates experimental autoimmune encephalomyelitis with reduced number of Foxp3+ CD4+ regulatory T cells. Immunology 2013; 140: 430–440.

    CAS  PubMed  Google Scholar 

  104. Sharma D, Malik A, Steury MD, Lucas PC, Parameswaran N . Protective role of beta-arrestin2 in colitis through modulation of T-cell activation. Inflamm Bowel Dis 2015, e-pub ahead of print 20 August 2015; doi:10.1097/MIB.0000000000000563.

    PubMed  Google Scholar 

  105. Liu Y, Wang GY, Liu SK, Yang MY, Ma LB, Li K et al. beta-arrestin2 stimulates interleukin-17 production and expression of CD4+ T lymphocytes in a murine asthma model. Iran J Allergy Asthma Immunol 2011; 10: 171–182.

    CAS  PubMed  Google Scholar 

  106. Wang G, Liu Y, Yang M, Liu S, Ma L, Gong S et al. Effects of beta-arrestin 2 on cytokine production of CD4+ T lymphocytes of mice with allergic asthma. Indian J Exp Biol 2011; 49: 585–593.

    CAS  PubMed  Google Scholar 

  107. Li J, Wei B, Guo A, Liu C, Huang S, Du F et al. Deficiency of beta-arrestin1 ameliorates collagen-induced arthritis with impaired TH17 cell differentiation. Proc Natl Acad Sci USA 2013; 110: 7395–7400.

    CAS  PubMed  Google Scholar 

  108. Li H, Chen L, Zhang Y, Lesage G, Zhang Y, Wu Y et al. Chronic stress promotes lymphocyte reduction through TLR2 mediated PI3K signaling in a beta-arrestin 2 dependent manner. J Neuroimmunol 2011; 233: 73–79.

    CAS  PubMed  Google Scholar 

  109. Man SM, Kanneganti TD . Regulation of inflammasome activation. Immunol Rev 2015; 265: 6–21.

    CAS  PubMed  Google Scholar 

  110. Shaw PJ, McDermott MF, Kanneganti TD . Inflammasomes and autoimmunity. Trends Mol Med 2011; 17: 57–64.

    CAS  PubMed  Google Scholar 

  111. Mao K, Chen S, Wang Y, Zeng Y, Ma Y, Hu Y et al. beta-arrestin1 is critical for the full activation of NLRP3 and NLRC4 inflammasomes. J Immunol 2015; 194: 1867–1873.

    CAS  PubMed  Google Scholar 

  112. Ohguro H, Chiba S, Igarashi Y, Matsumoto H, Akino T, Palczewski K . Beta-arrestin and arrestin are recognized by autoantibodies in sera from multiple sclerosis patients. Proc Natl Acad Sci USA 1993; 90: 3241–3245.

    CAS  PubMed  Google Scholar 

  113. Forooghian F, Cheung RK, Smith WC, O'Connor P, Dosch HM . Enolase and arrestin are novel nonmyelin autoantigens in multiple sclerosis. J Clin Immunol 2007; 27: 388–396.

    CAS  PubMed  Google Scholar 

  114. Bittner S, Afzali AM, Wiendl H, Meuth SG . Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. J Vis Exp 2014; 86: 51275.

    Google Scholar 

  115. Tsutsui S, Vergote D, Shariat N, Warren K, Ferguson SS, Power C . Glucocorticoids regulate innate immunity in a model of multiple sclerosis: reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells. FASEB J 2008; 22: 786–796.

    CAS  PubMed  Google Scholar 

  116. Coureuil M, Lecuyer H, Scott MG, Boularan C, Enslen H, Soyer M et al. Meningococcus hijacks a β2-adrenoceptor/β-Arrestin pathway to cross brain microvasculature endothelium. Cell 2010; 143: 1149–1160.

    CAS  PubMed  Google Scholar 

  117. Xia R, Hu Z, Sun Y, Chen S, Gu M, Zhou Y et al. Overexpression of beta-arrestin 2 in peripheral blood mononuclear cells of patients with cryptococcal meningitis. J Interferon Cytokine Res 2010; 30: 155–162.

    CAS  PubMed  Google Scholar 

  118. Nials AT, Uddin S . Mouse models of allergic asthma: acute and chronic allergen challenge. Dis Model Mech 2008; 1: 213–220.

    CAS  PubMed  Google Scholar 

  119. Hollingsworth JW, Theriot BS, Li Z, Lawson BL, Sunday M, Schwartz DA et al. Both Hematopoietic-derived and non hematopoietic-derived β-arrestin regulates murine allergic airway disease. Am J Respir Cell Mol Biol 2010; 43: 269–275.

    CAS  PubMed  Google Scholar 

  120. Nichols HL, Saffeddine M, Theriot BS, Hegde A, Polley D, El-Mays T et al. β-Arrestin-2 mediates the proinflammatory effects of proteinase-activated receptor-2 in the airway. Proc Natl Acad Sci USA 2012; 109: 16660–16665.

    CAS  PubMed  Google Scholar 

  121. Chen M, Hegde A, Choi YH, Theriot BS, Premont RT, Chen W et al. Genetic deletion of beta-arrestin-2 mitigates established airway hyperresponsiveness in a murine asthma model. Am J Respir Cell Mol Biol 2015; 53: 346–354.

    PubMed  Google Scholar 

  122. Khachigian LM . Collagen antibody-induced arthritis. Nat Protoc 2006; 1: 2512–2516.

    CAS  PubMed  Google Scholar 

  123. Li P, Cook JA, Gilkeson GS, Luttrell LM, Wang L, Borg KT et al. Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: isoform specific regulation of inflammation. Mol Immunol 2011; 49: 64–74.

    PubMed  Google Scholar 

  124. Campo GM, Avenoso A, D'Ascola A, Scuruchi M, Calatroni A, Campo S . Beta-arrestin-2 negatively modulates inflammation response in mouse chondrocytes induced by 4-mer hyaluronan oligosaccharide. Mol Cell Biochem 2015; 399: 201–208.

    CAS  PubMed  Google Scholar 

  125. Low D, Nguyen DD, Mizoguchi E . Animal models of ulcerative colitis and their application in drug research. Drug Des Devel Ther 2013; 7: 1341–1357.

    PubMed  Google Scholar 

  126. Lee T, Lee E, Irwin R, Lucas PC, McCabe LR, Parameswaran N . beta-Arrestin-1 deficiency protects mice from experimental colitis. Am J Pathol 2013; 182: 1114–1123.

    CAS  PubMed  Google Scholar 

  127. Zeng LX, Tao J, Liu HL, Tan SW, Yang YD, Peng XJ et al. [beta]-Arrestin2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis. Mucosal Immunol 2014; 8: 683–695.

    PubMed  Google Scholar 

  128. Chuang YH, Ridgway WM, Ueno Y, Gershwin ME . Animal models of primary biliary cirrhosis. Clin Liver Dis 2008; 12: 333–347 ix.

    PubMed  Google Scholar 

  129. Hu Z, Huang Y, Liu Y, Sun Y, Zhou Y, Gu M et al. beta-Arrestin 1 modulates functions of autoimmune T cells from primary biliary cirrhosis patients. J Clin Immunol 2011; 31: 346–355.

    CAS  PubMed  Google Scholar 

  130. Lymperopoulos A . GRK2 and beta-arrestins in cardiovascular disease: something old, something new. Am J Cardiovasc Dis 2011; 1: 126–137.

    CAS  PubMed  Google Scholar 

  131. 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 USA 2007; 104: 16657–16662.

    CAS  PubMed  Google Scholar 

  132. Most P, Pleger ST, Volkers M, Heidt B, Boerries M, Weichenhan D et al. Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. J Clin Invest 2004; 114: 1550–1563.

    CAS  PubMed  Google Scholar 

  133. Lymperopoulos A, Rengo G, Zincarelli C, Kim J, Koch WJ . Adrenal beta-arrestin 1 inhibition in vivo attenuates post-myocardial infarction progression to heart failure and adverse remodeling via reduction of circulating aldosterone levels. J Am Coll Cardiol 2011; 57: 356–365.

    CAS  PubMed  Google Scholar 

  134. Bathgate-Siryk A, Dabul S, Pandya K, Walklett K, Rengo G, Cannavo A et al. Negative impact of beta-arrestin-1 on post-myocardial infarction heart failure via cardiac and adrenal-dependent neurohormonal mechanisms. Hypertension 2014; 63: 404–412.

    CAS  PubMed  Google Scholar 

  135. Watari K, Nakaya M, Nishida M, Kim KM, Kurose H . beta-arrestin2 in infiltrated macrophages inhibits excessive inflammation after myocardial infarction. PLoS One 2013; 8: e68351.

    CAS  PubMed  Google Scholar 

  136. Selman M, Thannickal VJ, Pardo A, Zisman DA, Martinez FJ, Lynch JP 3rd . Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches. Drugs 2004; 64: 405–430.

    CAS  PubMed  Google Scholar 

  137. King TE Jr, Pardo A, Selman M . Idiopathic pulmonary fibrosis. Lancet 2011; 378: 1949–1961.

    PubMed  Google Scholar 

  138. Moore BB, Hogaboam CM . Murine models of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2008; 294: L152–L160.

    CAS  PubMed  Google Scholar 

  139. Lovgren AK, Kovacs JJ, Xie T, Potts EN, Li Y, Foster WM et al. beta-arrestin deficiency protects against pulmonary fibrosis in mice and prevents fibroblast invasion of extracellular matrix. Sci Transl Med 2011; 3: 74ra23.

    PubMed  Google Scholar 

  140. Rieber N, Hector A, Carevic M, Hartl D . Current concepts of immune dysregulation in cystic fibrosis. Int J Biochem Cell Biol 2014; 52: 108–112.

    CAS  PubMed  Google Scholar 

  141. White NM, Jiang D, Burgess JD, Bederman IR, Previs SF, Kelley TJ . Altered cholesterol homeostasis in cultured and in vivo models of cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2007; 292: L476–L486.

    CAS  PubMed  Google Scholar 

  142. Manson ME, Corey DA, White NM, Kelley TJ . cAMP-mediated regulation of cholesterol accumulation in cystic fibrosis and Niemann-Pick type C cells. Am J Physiol Lung Cell Mol Physiol 2008; 295: L809–L819.

    CAS  PubMed  Google Scholar 

  143. Manson ME, Corey DA, Rymut SM, Kelley TJ . beta-arrestin-2 regulation of the cAMP response element binding protein. Biochemistry 2011; 50: 6022–6029.

    CAS  PubMed  Google Scholar 

  144. Manson ME, Corey DA, Bederman I, Burgess JD, Kelley TJ . Regulatory role of beta-arrestin-2 in cholesterol processing in cystic fibrosis epithelial cells. J Lipid Res 2012; 53: 1268–1276.

    CAS  PubMed  Google Scholar 

  145. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 2003; 9: 352–355.

    CAS  Google Scholar 

  146. Benyo Z, Gille A, Kero J, Csiky M, Suchankova MC, Nusing RM et al. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest 2005; 115: 3634–3640.

    CAS  PubMed  Google Scholar 

  147. Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM et al. β-Arrestin1 mediates nicotinic acid–induced flushing, but not its antilipolytic effect, in mice. J Clin Invest 2009; 119: 1312–1321.

    CAS  PubMed  Google Scholar 

  148. Lauring B, Taggart AK, Tata JR, Dunbar R, Caro L, Cheng K et al. Niacin lipid efficacy is independent of both the niacin receptor GPR109A and free fatty acid suppression. Sci Transl Med 2012; 4: 148ra115.

    PubMed  Google Scholar 

  149. Villa P, Ghezzi P . Animal models of endotoxic shock. Methods Mol Med 2004; 98: 199–206.

    CAS  PubMed  Google Scholar 

  150. Porter KJ, Gonipeta B, Parvataneni S, Appledorn DM, Patial S, Sharma D et al. Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by β-arrestins. J Cell Physiol 2010; 225: 406–416.

    CAS  PubMed  Google Scholar 

  151. Li H, Hu D, Fan H, Zhang Y, LeSage GD, Caudle Y et al. beta-Arrestin 2 negatively regulates TLR4-triggered inflammatory signaling via targeting p38 MAPK and IL-10. J Biol Chem 2014; 289: 23075–23085.

    CAS  PubMed  Google Scholar 

  152. Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ . Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology 2014; 146: 1763–1774.

    CAS  PubMed  Google Scholar 

  153. Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW 3rd, Bland KI et al. Cecal ligation and puncture. Shock 2005; 24 (Suppl 1): 52–57.

    PubMed  Google Scholar 

  154. Ayala A, Song GY, Chung CS, Redmond KM, Chaudry IH . Immune depression in polymicrobial sepsis: the role of necrotic (injured) tissue and endotoxin. Crit Care Med 2000; 28: 2949–2955.

    CAS  PubMed  Google Scholar 

  155. 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; 278: 51334–51339.

    CAS  PubMed  Google Scholar 

  156. Zhao M, Wimmer A, Trieu K, Discipio RG, Schraufstatter IU . Arrestin regulates MAPK activation and prevents NADPH oxidase-dependent death of cells expressing CXCR2. J Biol Chem 2004; 279: 49259–49267.

    CAS  PubMed  Google Scholar 

  157. Revankar CM, Vines CM, Cimino DF, Prossnitz ER . Arrestins block G protein-coupled receptor-mediated apoptosis. J Biol Chem 2004; 279: 24578–24584.

    CAS  PubMed  Google Scholar 

  158. Zhang Z, Hao J, Zhao Z, Ben P, Fang F, Shi L et al. β-Arrestins facilitate ubiquitin-dependent degradation of apoptosis signal-regulating kinase 1 (ASK1) and attenuate H2O2-induced apoptosis. Cellular Signalling 2009; 21: 1195–1206.

    CAS  PubMed  Google Scholar 

  159. Ahn S, Kim J, Hara MR, Ren XR, Lefkowitz RJ . β-Arrestin-2 mediates anti-apoptotic signaling through regulation of BAD phosphorylation. J Biol Chem 2009; 284: 8855–8865.

    CAS  PubMed  Google Scholar 

  160. Zhao M, Zhou G, Zhang Y, Chen T, Sun X, Stuart C et al. beta-arrestin2 inhibits opioid-induced breast cancer cell death through Akt and caspase-8 pathways. Neoplasma 2009; 56: 108–113.

    CAS  PubMed  Google Scholar 

  161. Moorman J, Zhang Y, Liu B, LeSage G, Chen Y, Stuart C et al. HIV-1 gp120 primes lymphocytes for opioid-induced, β-arrestin 2-dependent apoptosis. Biochim Biophys Acta 2009; 1793: 1366–1371.

    CAS  PubMed  Google Scholar 

  162. Qi S, Xin Y, Qi Z, Xu Y, Diao Y, Lan L et al. HSP27 phosphorylation modulates TRAIL-induced activation of Src-Akt/ERK signaling through interaction with beta-arrestin2. Cell Signal 2014; 26: 594–602.

    CAS  PubMed  Google Scholar 

  163. Sun X, Zhang Y, Wang J, Wei L, Li H, Hanley G et al. Beta-arrestin 2 modulates resveratrol-induced apoptosis and regulation of Akt/GSK3ss pathways. Biochim Biophys Acta 2010; 1800: 912–918.

    CAS  PubMed  Google Scholar 

  164. Zhu Z, Reiser G . PAR-1 activation rescues astrocytes through the PI3K/Akt signaling pathway from chemically induced apoptosis that is exacerbated by gene silencing of beta-arrestin 1. Neurochem Int 2014; 67: 46–56.

    CAS  PubMed  Google Scholar 

  165. Rojanathammanee L, Harmon EB, Grisanti LA, Govitrapong P, Ebadi M, Grove BD et al. The 27-kDa heat shock protein confers cytoprotective effects through a beta 2-adrenergic receptor agonist-initiated complex with beta-arrestin. Mol Pharmacol 2009; 75: 855–865.

    CAS  PubMed  Google Scholar 

  166. Quoyer J, Longuet C, Broca C, Linck N, Costes S, Varin E et al. GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells. J Biol Chem 2010; 285: 1989–2002.

    CAS  PubMed  Google Scholar 

  167. Wu JX, Shan FX, Zheng JN, Pei DS . β-arrestin promotes c-Jun N-terminal kinase mediated apoptosis via a GABA(B)R·β-arrestin·JNK signaling module. Asian Pac J Cancer Prev 2014; 15: 1041–1046.

    PubMed  Google Scholar 

  168. 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; 278: 41581–41584.

    CAS  PubMed  Google Scholar 

  169. Barlic J, Khandaker MH, Mahon E, Andrews J, DeVries ME, Mitchell GB et al. β-Arrestins regulate interleukin-8-induced CXCR1 internalization. J Biol Chem 1999; 274: 16287–16294.

    CAS  PubMed  Google Scholar 

  170. Aramori I, Zhang J, Ferguson SSG, Bieniasz PD, Cullen BR, Caron MG . Molecular mechanism of desensitization of the chemokine receptor CCR5: receptor signaling and internalization are dissociable from its role as an HIV co-receptor. EMBO J 1997; 16: 4606–4616.

    CAS  PubMed  Google Scholar 

  171. Huttenrauch F, Pollok-Kopp B, Oppermann M . G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers. J Biol Chem 2005; 280: 37503–37515.

    PubMed  Google Scholar 

  172. Dery O, Thoma MS, Wong H, Grady EF, Bunnett NW . Trafficking of proteinase-activated receptor-2 and β-arrestin-1 tagged with green fluorescent protein. β-Arrestin-dependent endocytosis of a proteinase receptor. J Biol Chem 1999; 274: 18524–18535.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Research in Dr Parameswaran’s lab is supported by funding from the National Institutes of Health (Grants HL095637, AR055726 and AI099404).

Author information

Authors and Affiliations

  1. Department of Physiology and Division of Pathology, Michigan State University, East Lansing, MI, USA

    D Sharma & N Parameswaran

Authors
  1. D Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Parameswaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Parameswaran.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, D., Parameswaran, N. Multifaceted role of β-arrestins in inflammation and disease. Genes Immun 16, 499–513 (2015). https://doi.org/10.1038/gene.2015.37

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2015.37

This article is cited by

Search

Advanced search

Quick links