Arrestin beta 2

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Aliases ARRB2, ARB2, ARR2, BARR2, Arrestin beta 2
External IDs MGI: 99474 HomoloGene: 3183 GeneCards: 409
RNA expression pattern
PBB GE ARRB2 203388 at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 17: 4.71 – 4.72 Mb Chr 11: 70.43 – 70.44 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene.

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals,[1][2][3] as well as having signalling roles in their own right.[4][5][6][7][8] Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined.[9]

The protein may interact with the agonist DOI in 5-HT2A receptor signaling.[10][11]


Arrestin beta 2 has been shown to interact with


  1. ^ Breivogel CS, Lambert JM, Gerfin S, Huffman JW, Razdan RK (July 2008). "Sensitivity to Δ9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2-/- mice". Behavioural Pharmacology 19 (4): 298–307. doi:10.1097/FBP.0b013e328308f1e6. PMC 2751575. PMID 18622177. 
  2. ^ Li Y, Liu X, Liu C, Kang J, Yang J, Pei G, Wu C (March 2009). "Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter". International Journal of Molecular Sciences 10 (3): 954–63. doi:10.3390/ijms10030954. PMC 2672012. PMID 19399231. 
  3. ^ Zheng H, Loh HH, Law PY (January 2008). "β-Arrestin-Dependent μ-Opioid Receptor-Activated Extracellular Signal-Regulated Kinases (ERKs) Translocate to Nucleus in Contrast to G Protein-Dependent ERK Activation". Molecular Pharmacology 73 (1): 178–90. doi:10.1124/mol.107.039842. PMC 2253657. PMID 17947509. 
  4. ^ Ma L, Pei G (January 2007). "Beta-arrestin signaling and regulation of transcription". Journal of Cell Science 120 (Pt 2): 213–8. doi:10.1242/jcs.03338. PMID 17215450. 
  5. ^ Defea K (March 2008). "β-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction". British Journal of Pharmacology. 153 Suppl 1 (S1): S298–309. doi:10.1038/sj.bjp.0707508. PMC 2268080. PMID 18037927. 
  6. ^ Barki-Harrington L, Rockman HA (February 2008). "Beta-arrestins: multifunctional cellular mediators". Physiology (Bethesda, Md.) 23: 17–22. doi:10.1152/physiol.00042.2007. PMID 18268361. 
  7. ^ Patel PA, Tilley DG, Rockman HA (March 2009). "Physiologic and cardiac roles of beta-arrestins". Journal of Molecular and Cellular Cardiology 46 (3): 300–8. doi:10.1016/j.yjmcc.2008.11.015. PMID 19103204. 
  8. ^ Golan M, Schreiber G, Avissar S (2009). "Antidepressants, beta-arrestins and GRKs: from regulation of signal desensitization to intracellular multifunctional adaptor functions". Current Pharmaceutical Design 15 (14): 1699–708. doi:10.2174/138161209788168038. PMID 19442183. 
  9. ^ "Entrez Gene: ARRB2 arrestin, beta 2". 
  10. ^ Schmid CL, Raehal KM, Bohn LM (January 2008). "Agonist-directed signaling of the serotonin 2A receptor depends on β-arrestin-2 interactions in vivo". Proc. Natl. Acad. Sci. U.S.A. 105 (3): 1079–84. doi:10.1073/pnas.0708862105. PMC 2242710. PMID 18195357. 
  11. ^ Abbas A, Roth BL (January 2008). "Arresting serotonin". Proc. Natl. Acad. Sci. U.S.A. 105 (3): 831–2. doi:10.1073/pnas.0711335105. PMC 2242676. PMID 18195368. 
  12. ^ Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS (March 1999). "The β2-adrenergic receptor/βarrestin complex recruits the clathrin adaptor AP-2 during endocytosis". Proc. Natl. Acad. Sci. U.S.A. 96 (7): 3712–7. doi:10.1073/pnas.96.7.3712. PMC 22359. PMID 10097102. 
  13. ^ Kim YM, Benovic JL (August 2002). "Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2 in G protein-coupled receptor trafficking". J. Biol. Chem. 277 (34): 30760–8. doi:10.1074/jbc.M204528200. PMID 12070169. 
  14. ^ Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, Lefkowitz RJ (November 2001). "beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis". J. Biol. Chem. 276 (45): 42509–13. doi:10.1074/jbc.M108399200. PMID 11533043. 
  15. ^ Wang P, Gao H, Ni Y, Wang B, Wu Y, Ji L, Qin L, Ma L, Pei G (February 2003). "Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2". J. Biol. Chem. 278 (8): 6363–70. doi:10.1074/jbc.M210350200. PMID 12488444. 
  16. ^ Wang P, Wu Y, Ge X, Ma L, Pei G (March 2003). "Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus". J. Biol. Chem. 278 (13): 11648–53. doi:10.1074/jbc.M208109200. PMID 12538596. 
  17. ^ Shenoy SK, Xiao K, Venkataramanan V, Snyder PM, Freedman NJ, Weissman AM (August 2008). "Nedd4 Mediates Agonist-dependent Ubiquitination, Lysosomal Targeting, and Degradation of the β2-Adrenergic Receptor". J. Biol. Chem. 283 (32): 22166–76. doi:10.1074/jbc.M709668200. PMC 2494938. PMID 18544533. 
  18. ^ Bhattacharya M, Anborgh PH, Babwah AV, Dale LB, Dobransky T, Benovic JL, Feldman RD, Verdi JM, Rylett RJ, Ferguson SS (August 2002). "Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization". Nat. Cell Biol. 4 (8): 547–55. doi:10.1038/ncb821. PMID 12105416. 

Further reading[edit]

  • Lefkowitz RJ (1998). "G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization". J. Biol. Chem. 273 (30): 18677–80. doi:10.1074/jbc.273.30.18677. PMID 9668034. 
  • Attramadal H, Arriza JL, Aoki C, et al. (1992). "Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family". J. Biol. Chem. 267 (25): 17882–90. PMID 1517224. 
  • Rapoport B, Kaufman KD, Chazenbalk GD (1992). "Cloning of a member of the arrestin family from a human thyroid cDNA library". Mol. Cell. Endocrinol. 84 (3): R39–43. doi:10.1016/0303-7207(92)90038-8. PMID 1587386. 
  • Calabrese G, Sallese M, Stornaiuolo A, et al. (1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes". Genomics 23 (1): 286–8. doi:10.1006/geno.1994.1497. PMID 7695743. 
  • Parruti G, Peracchia F, Sallese M, et al. (1993). "Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing". J. Biol. Chem. 268 (13): 9753–61. PMID 8486659. 
  • Le Gouill C, Parent JL, Rola-Pleszczynski M, Stanková J (1997). "Role of the Cys90, Cys95 and Cys173 residues in the structure and function of the human platelet-activating factor receptor". FEBS Lett. 402 (2–3): 203–8. doi:10.1016/S0014-5793(96)01531-1. PMID 9037196. 
  • Barak LS, Ferguson SS, Zhang J, Caron MG (1997). "A beta-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation". J. Biol. Chem. 272 (44): 27497–500. doi:10.1074/jbc.272.44.27497. PMID 9346876. 
  • Laporte SA, Oakley RH, Zhang J, et al. (1999). "The β2-adrenergic receptor/βarrestin complex recruits the clathrin adaptor AP-2 during endocytosis". Proc. Natl. Acad. Sci. U.S.A. 96 (7): 3712–7. doi:10.1073/pnas.96.7.3712. PMC 22359. PMID 10097102. 
  • Cheng ZJ, Zhao J, Sun Y, et al. (2000). "beta-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. 275 (4): 2479–85. doi:10.1074/jbc.275.4.2479. PMID 10644702. 
  • Lin F, Wang H, Malbon CC (2000). "Gravin-mediated formation of signaling complexes in beta 2-adrenergic receptor desensitization and resensitization". J. Biol. Chem. 275 (25): 19025–34. doi:10.1074/jbc.275.25.19025. PMID 10858453. 
  • McDonald PH, Chow CW, Miller WE, et al. (2000). "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3". Science 290 (5496): 1574–7. doi:10.1126/science.290.5496.1574. PMID 11090355. 
  • Luttrell LM, Roudabush FL, Choy EW, et al. (2001). "Activation and targeting of extracellular signal-regulated kinases by β-arrestin scaffolds". Proc. Natl. Acad. Sci. U.S.A. 98 (5): 2449–54. doi:10.1073/pnas.041604898. PMC 30158. PMID 11226259. 
  • Cen B, Yu Q, Guo J, et al. (2001). "Direct binding of beta-arrestins to two distinct intracellular domains of the delta opioid receptor". J. Neurochem. 76 (6): 1887–94. doi:10.1046/j.1471-4159.2001.00204.x. PMID 11259507. 
  • Oakley RH, Laporte SA, Holt JA, et al. (2001). "Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis*". J. Biol. Chem. 276 (22): 19452–60. doi:10.1074/jbc.M101450200. PMID 11279203. 
  • Miller WE, McDonald PH, Cai SF, et al. (2001). "Identification of a motif in the carboxyl terminus of beta -arrestin2 responsible for activation of JNK3". J. Biol. Chem. 276 (30): 27770–7. doi:10.1074/jbc.M102264200. PMID 11356842. 
  • Claing A, Chen W, Miller WE, et al. (2001). "beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis". J. Biol. Chem. 276 (45): 42509–13. doi:10.1074/jbc.M108399200. PMID 11533043. 
  • Hilairet S, Bélanger C, Bertrand J, et al. (2001). "Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin". J. Biol. Chem. 276 (45): 42182–90. doi:10.1074/jbc.M107323200. PMID 11535606. 
  • 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 (5545): 1307–13. doi:10.1126/science.1063866. PMID 11588219. 
  • Chen Z, Dupré DJ, Le Gouill C, et al. (2002). "Agonist-induced internalization of the platelet-activating factor receptor is dependent on arrestins but independent of G-protein activation. Role of the C terminus and the (D/N)PXXY motif". J. Biol. Chem. 277 (9): 7356–62. doi:10.1074/jbc.M110058200. PMID 11729201. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.