Arrestin beta 2 explained

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-HT_2A receptor signaling.^{[10] [11]}

Arrestin beta 2 is crucial for the development of tolerance to morphine and other opioids.

Interactions

Arrestin beta 2 has been shown to interact with

• AP2B1,^{[12] [13]}
• PSCD2,^[14]
• Mdm2,^{[15] [16] [17]} and
• RALGDS.^[18]

Further reading

• Lefkowitz RJ . G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization . The Journal of Biological Chemistry . 273 . 30 . 18677–80 . July 1998 . 9668034 . 10.1074/jbc.273.30.18677 . free .
• Attramadal H, Arriza JL, Aoki C, Dawson TM, Codina J, Kwatra MM, Snyder SH, Caron MG, Lefkowitz RJ . Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family . The Journal of Biological Chemistry . 267 . 25 . 17882–90 . September 1992 . 10.1016/S0021-9258(19)37125-X . 1517224 . free .
• Rapoport B, Kaufman KD, Chazenbalk GD . Cloning of a member of the arrestin family from a human thyroid cDNA library . Molecular and Cellular Endocrinology . 84 . 3 . R39-43 . April 1992 . 1587386 . 10.1016/0303-7207(92)90038-8 . 1964362 .
• Calabrese G, Sallese M, Stornaiuolo A, Stuppia L, Palka G, De Blasi A . Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes . Genomics . 23 . 1 . 286–8 . September 1994 . 7695743 . 10.1006/geno.1994.1497 .
• Parruti G, Peracchia F, Sallese M, Ambrosini G, Masini M, Rotilio D, De Blasi A . Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing . The Journal of Biological Chemistry . 268 . 13 . 9753–61 . May 1993 . 10.1016/S0021-9258(18)98412-7 . 8486659 . free .
• Le Gouill C, Parent JL, Rola-Pleszczynski M, Stanková J . Role of the Cys90, Cys95 and Cys173 residues in the structure and function of the human platelet-activating factor receptor . FEBS Letters . 402 . 2–3 . 203–8 . February 1997 . 9037196 . 10.1016/S0014-5793(96)01531-1 . 21074692 . free . 1997FEBSL.402..203L .
• Barak LS, Ferguson SS, Zhang J, Caron MG . A beta-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation . The Journal of Biological Chemistry . 272 . 44 . 27497–500 . October 1997 . 9346876 . 10.1074/jbc.272.44.27497 . free.
• Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS . The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis . Proceedings of the National Academy of Sciences of the United States of America . 96 . 7 . 3712–7 . March 1999 . 10097102 . 22359 . 10.1073/pnas.96.7.3712 . 1999PNAS...96.3712L . free .
• Cheng ZJ, Zhao J, Sun Y, Hu W, Wu YL, Cen B, Wu GX, Pei G . beta-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4 . The Journal of Biological Chemistry . 275 . 4 . 2479–85 . January 2000 . 10644702 . 10.1074/jbc.275.4.2479 . free .
• Lin F, ((Wang Hy)), Malbon CC . Gravin-mediated formation of signaling complexes in beta 2-adrenergic receptor desensitization and resensitization . The Journal of Biological Chemistry . 275 . 25 . 19025–34 . June 2000 . 10858453 . 10.1074/jbc.275.25.19025 . free .
• McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME, Lin FT, Davis RJ, Lefkowitz RJ . Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3 . Science . 290 . 5496 . 1574–7 . November 2000 . 11090355 . 10.1126/science.290.5496.1574 . 2000Sci...290.1574M .
• Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, Pierce KL, Lefkowitz RJ . Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds . Proceedings of the National Academy of Sciences of the United States of America . 98 . 5 . 2449–54 . February 2001 . 11226259 . 30158 . 10.1073/pnas.041604898 . 2001PNAS...98.2449L . free .
• Cen B, Yu Q, Guo J, Wu Y, Ling K, Cheng Z, Ma L, Pei G . Direct binding of beta-arrestins to two distinct intracellular domains of the delta opioid receptor . Journal of Neurochemistry . 76 . 6 . 1887–94 . March 2001 . 11259507 . 10.1046/j.1471-4159.2001.00204.x . 83485138 . free .
• Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG . Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis* . The Journal of Biological Chemistry . 276 . 22 . 19452–60 . June 2001 . 11279203 . 10.1074/jbc.M101450200 . free .
• 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 . The Journal of Biological Chemistry . 276 . 30 . 27770–7 . July 2001 . 11356842 . 10.1074/jbc.M102264200 . free .
• Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, Lefkowitz RJ . beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis . The Journal of Biological Chemistry . 276 . 45 . 42509–13 . November 2001 . 11533043 . 10.1074/jbc.M108399200 . free .
• Hilairet S, Bélanger C, Bertrand J, Laperrière A, Foord SM, Bouvier M . Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin . The Journal of Biological Chemistry . 276 . 45 . 42182–90 . November 2001 . 11535606 . 10.1074/jbc.M107323200 . free .
• Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ . Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin . Science . 294 . 5545 . 1307–13 . November 2001 . 11588219 . 10.1126/science.1063866 . 2001Sci...294.1307S . 23486946 . free .
• Chen Z, Dupré DJ, Le Gouill C, Rola-Pleszczynski M, Stanková J . 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 . The Journal of Biological Chemistry . 277 . 9 . 7356–62 . March 2002 . 11729201 . 10.1074/jbc.M110058200 . free .

Notes and References

1. Breivogel CS, Lambert JM, Gerfin S, Huffman JW, Razdan RK . Sensitivity to delta9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2 -/- mice . Behavioural Pharmacology . 19 . 4 . 298–307 . July 2008 . 18622177 . 2751575 . 10.1097/FBP.0b013e328308f1e6 .
2. Li Y, Liu X, Liu C, Kang J, Yang J, Pei G, Wu C . Improvement of morphine-mediated analgesia by inhibition of β-arrestin2 expression in mice periaqueductal gray matter . International Journal of Molecular Sciences . 10 . 3 . 954–63 . March 2009 . 19399231 . 2672012 . 10.3390/ijms10030954 . free .
3. Zheng H, Loh HH, Law PY . Horace Loh. Beta-arrestin-dependent mu-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 . January 2008 . 17947509 . 2253657 . 10.1124/mol.107.039842 .
4. Ma L, Pei G . Beta-arrestin signaling and regulation of transcription . Journal of Cell Science . 120 . Pt 2 . 213–8 . January 2007 . 17215450 . 10.1242/jcs.03338 . free .
5. Defea K . Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction . British Journal of Pharmacology . 153 Suppl 1 . S1 . S298-309 . March 2008 . 18037927 . 2268080 . 10.1038/sj.bjp.0707508 .
6. Barki-Harrington L, Rockman HA . Beta-arrestins: multifunctional cellular mediators . Physiology . 23 . 17–22 . February 2008 . 18268361 . 10.1152/physiol.00042.2007 .
7. Patel PA, Tilley DG, Rockman HA . Physiologic and cardiac roles of beta-arrestins . Journal of Molecular and Cellular Cardiology . 46 . 3 . 300–8 . March 2009 . 19103204 . 10.1016/j.yjmcc.2008.11.015 .
8. Golan M, Schreiber G, Avissar S . Antidepressants, beta-arrestins and GRKs: from regulation of signal desensitization to intracellular multifunctional adaptor functions . Current Pharmaceutical Design . 15 . 14 . 1699–708 . 2009 . 19442183 . 10.2174/138161209788168038 .
9. Web site: ARRB2 arrestin beta 2 [Homo sapiens (human) ]]. National Center for Biotechnology Information.
10. Schmid CL, Raehal KM, Bohn LM . Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo . Proceedings of the National Academy of Sciences of the United States of America . 105 . 3 . 1079–84 . January 2008 . 18195357 . 2242710 . 10.1073/pnas.0708862105 . free .
11. Abbas A, Roth BL. Bryan Roth . Arresting serotonin . Proceedings of the National Academy of Sciences of the United States of America . 105 . 3 . 831–2 . January 2008 . 18195368 . 2242676 . 10.1073/pnas.0711335105 . 2008PNAS..105..831A . free .
12. Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS . The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis . Proceedings of the National Academy of Sciences of the United States of America . 96 . 7 . 3712–7 . March 1999 . 10097102 . 22359 . 10.1073/pnas.96.7.3712 . 1999PNAS...96.3712L . free .
13. Kim YM, Benovic JL . Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2 in G protein-coupled receptor trafficking . The Journal of Biological Chemistry . 277 . 34 . 30760–8 . August 2002 . 12070169 . 10.1074/jbc.M204528200 . free .
14. Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT, Lefkowitz RJ . beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis . The Journal of Biological Chemistry . 276 . 45 . 42509–13 . November 2001 . 11533043 . 10.1074/jbc.M108399200 . free .
15. Wang P, Gao H, Ni Y, Wang B, Wu Y, Ji L, Qin L, Ma L, Pei G . Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2 . The Journal of Biological Chemistry . 278 . 8 . 6363–70 . February 2003 . 12488444 . 10.1074/jbc.M210350200 . free .
16. 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 . The Journal of Biological Chemistry . 278 . 13 . 11648–53 . March 2003 . 12538596 . 10.1074/jbc.M208109200 . free .
17. Shenoy SK, Xiao K, Venkataramanan V, Snyder PM, Freedman NJ, Weissman AM . Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor . The Journal of Biological Chemistry . 283 . 32 . 22166–76 . August 2008 . 18544533 . 2494938 . 10.1074/jbc.M709668200 . free .
18. Bhattacharya M, Anborgh PH, Babwah AV, Dale LB, Dobransky T, Benovic JL, Feldman RD, Verdi JM, Rylett RJ, Ferguson SS . Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization . Nature Cell Biology . 4 . 8 . 547–55 . August 2002 . 12105416 . 10.1038/ncb821 . 20784208 .