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Gene Review

Arrb2  -  arrestin, beta 2

Mus musculus

Synonyms: AI326910, AW122872, Arrestin beta-2, Beta-arrestin-2, beta arr2, ...
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Disease relevance of Arrb2

  • Endotoxin-treated beta-arrestin 2-deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock [1].
  • Studies in mice have shown that beta-arrestin-2 plays an important role in the development of morphine-induced tolerance, constipation, and respiratory depression [2].

High impact information on Arrb2

  • Importantly, canonical cAMP-mediated dopamine-receptor signaling is not inhibited in the absence of beta-arrestin 2 [3].
  • Furthermore, this function of beta-arrestin 2 is important for the expression of dopamine-associated behaviors, thus implicating beta-arrestin 2 as a positive mediator of dopaminergic synaptic transmission and a potential pharmacological target for dopamine-related psychiatric disorders [3].
  • However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug [4].
  • These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in regulating the function of a specific GPCR, the muOR [5].
  • It has been reported recently that T cells lacking beta-arrestin-2, a G protein-coupled receptor regulatory protein, demonstrate impaired migration in vitro [6].

Biological context of Arrb2

  • Histomorphometry showed that PTH-stimulated periosteal bone formation was 2-fold higher in beta-arr2(-/-) compared with WT [7].
  • The Cys328/329-Ser mutant, which is constitutively active in the absence of ligand, exhibited enhanced receptor phosphorylation under both basal and agonist-stimulated conditions and was more effectively desensitized and internalized via a beta-arrestin-2 mediated pathway compared with the wild-type 5-HT4a [8].
  • Differential regulation of beta-arrestin 1 and beta-arrestin 2 gene expression in rat brain by morphine [9].

Anatomical context of Arrb2


Associations of Arrb2 with chemical compounds

  • At 30 min, endogenous beta-arrestins reduced TRH-stimulated inositol phosphate production by 48% (beta-arrestin-1), 71% (beta-arrestin-2), and 84% (beta-arrestins-1 and -2) [11].
  • The present result suggests that beta-arrestin-2 may tonically down-regulate a selected population of mu-opioid receptors activated by endomorphin-1 or DAMGO in the mouse spinal cord [12].
  • Intrathecal (i.t.) pretreatment with beta-arrestin-2 antibody potentiated the antinociception induced by i.t.-administered mu-opioid receptor agonists [D-Ala(2),NMePhe(4),Gly-ol(5)]enkephalin (DAMGO) and endomorphin-1, but not endomorphin-2, the delta-opioid receptor agonist [D-Ala(2)]deltorphin II or the kappa-opioid receptor agonist U50,488H [12].
  • Receptor functionality was assessed by Ang II-stimulated beta-arrestin 2 translocation and showed an Ang II-mediated response in wild type but not (AT(1A) [-/ -], AT(1B) [-/-]) cells [13].

Other interactions of Arrb2

  • Comparison of the ability of the two beta-arrestins to sequester the beta(2)-AR revealed beta-arrestin 2 to be 100-fold more potent than beta-arrestin 1 [14].
  • Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that muOR desensitization was impaired [5].
  • We have previously shown that adaptor protein beta-arrestin-2 (betaarr2) plays a crucial role in transducing signals mediated through CXCR2 [15].

Analytical, diagnostic and therapeutic context of Arrb2


  1. Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. Wang, Y., Tang, Y., Teng, L., Wu, Y., Zhao, X., Pei, G. Nat. Immunol. (2006) [Pubmed]
  2. An opioid agonist that does not induce micro-opioid receptor--arrestin interactions or receptor internalization. Groer, C.E., Tidgewell, K., Moyer, R.A., Harding, W.W., Rothman, R.B., Prisinzano, T.E., Bohn, L.M. Mol. Pharmacol. (2007) [Pubmed]
  3. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Beaulieu, J.M., Sotnikova, T.D., Marion, S., Lefkowitz, R.J., Gainetdinov, R.R., Caron, M.G. Cell (2005) [Pubmed]
  4. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Bohn, L.M., Gainetdinov, R.R., Lin, F.T., Lefkowitz, R.J., Caron, M.G. Nature (2000) [Pubmed]
  5. Enhanced morphine analgesia in mice lacking beta-arrestin 2. Bohn, L.M., Lefkowitz, R.J., Gainetdinov, R.R., Peppel, K., Caron, M.G., Lin, F.T. Science (1999) [Pubmed]
  6. Beta-arrestin-2 regulates the development of allergic asthma. Walker, J.K., Fong, A.M., Lawson, B.L., Savov, J.D., Patel, D.D., Schwartz, D.A., Lefkowitz, R.J. J. Clin. Invest. (2003) [Pubmed]
  7. beta-Arrestin2 regulates the differential response of cortical and trabecular bone to intermittent PTH in female mice. Bouxsein, M.L., Pierroz, D.D., Glatt, V., Goddard, D.S., Cavat, F., Rizzoli, R., Ferrari, S.L. J. Bone Miner. Res. (2005) [Pubmed]
  8. Palmitoylation of the 5-hydroxytryptamine4a receptor regulates receptor phosphorylation, desensitization, and beta-arrestin-mediated endocytosis. Ponimaskin, E., Dumuis, A., Gaven, F., Barthet, G., Heine, M., Glebov, K., Richter, D.W., Oppermann, M. Mol. Pharmacol. (2005) [Pubmed]
  9. Differential regulation of beta-arrestin 1 and beta-arrestin 2 gene expression in rat brain by morphine. Fan, X.L., Zhang, J.S., Zhang, X.Q., Yue, W., Ma, L. Neuroscience (2003) [Pubmed]
  10. beta-Arrestin 2 expression determines the transcriptional response to lysophosphatidic acid stimulation in murine embryo fibroblasts. Gesty-Palmer, D., Shewy, H.E., Kohout, T.A., Luttrell, L.M. J. Biol. Chem. (2005) [Pubmed]
  11. Beta-arrestin mediates desensitization and internalization but does not affect dephosphorylation of the thyrotropin-releasing hormone receptor. Jones, B.W., Hinkle, P.M. J. Biol. Chem. (2005) [Pubmed]
  12. Involvement of beta-arrestin-2 in modulation of the spinal antinociception induced by mu-opioid receptor agonists in the mouse. Ohsawa, M., Mizoguchi, H., Narita, M., Nagase, H., Dun, N.J., Tseng, L.F. Neurosci. Lett. (2003) [Pubmed]
  13. Strategy for the development of a matched set of transport-competent, angiotensin receptor-deficient proximal tubule cell lines. Woost, P.G., Kolb, R.J., Finesilver, M., Mackraj, I., Imboden, H., Coffman, T.M., Hopfer, U. In Vitro Cell. Dev. Biol. Anim. (2006) [Pubmed]
  14. beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Kohout, T.A., Lin, F.S., Perry, S.J., Conner, D.A., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. Altered CXCR2 signaling in beta-arrestin-2-deficient mouse models. Su, Y., Raghuwanshi, S.K., Yu, Y., Nanney, L.B., Richardson, R.M., Richmond, A. J. Immunol. (2005) [Pubmed]
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