Gene Symbol: Arrb2
Description: arrestin, beta 2
Alias: BARRES, beta-arrestin-2
Species: rat
Products:     Arrb2

Top Publications

  1. Ahn S, Kim J, Hara M, Ren X, Lefkowitz R. {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation. J Biol Chem. 2009;284:8855-65 pubmed publisher
    ..These findings establish a key role for beta-arrestin-2 in mediating cellular cytoprotective functions by a 7-transmembrane receptor and define the biochemical pathways involved. ..
  2. Tzingounis A, von Zastrow M, Yudowski G. {Beta}-blocker drugs mediate calcium signaling in native central nervous system neurons by {beta}-arrestin-biased agonism. Proc Natl Acad Sci U S A. 2010;107:21028-33 pubmed publisher
    ..Our results support the emerging view of ?-arrestin-biased agonism as a significant mechanism of drug action and do so in CNS-derived neurons expressing only native receptors. ..
  3. Kim J, Ahn S, Rajagopal K, Lefkowitz R. Independent beta-arrestin2 and Gq/protein kinase Czeta pathways for ERK stimulated by angiotensin type 1A receptors in vascular smooth muscle cells converge on transactivation of the epidermal growth factor receptor. J Biol Chem. 2009;284:11953-62 pubmed publisher
  4. Castro Obregon S, Rao R, Del Rio G, Chen S, Poksay K, Rabizadeh S, et al. Alternative, nonapoptotic programmed cell death: mediation by arrestin 2, ERK2, and Nur77. J Biol Chem. 2004;279:17543-53 pubmed
    ..These results suggest that Nur77, which is regulated by a MAPK pathway activated via arrestin 2, modulates NK(1)R-mediated nonapoptotic pcd. ..
  5. 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;123:833-47 pubmed
  6. Cheng Z, Zhao J, Sun Y, Hu W, Wu Y, Cen B, et al. 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. 2000;275:2479-85 pubmed
  7. Macey T, Gurevich V, Neve K. Preferential Interaction between the dopamine D2 receptor and Arrestin2 in neostriatal neurons. Mol Pharmacol. 2004;66:1635-42 pubmed
    ..All three measures of receptor/arrestin interaction (colocalization, translocation, and coprecipitation) demonstrated selective agonist-induced interaction between the D2 receptor and arrestin2 in neurons. ..
  8. Kohout T, Lin F, Perry S, Conner D, Lefkowitz R. beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A. 2001;98:1601-6 pubmed
    ..These findings suggest that sequestration of various heptahelical receptors is regulated differently by the two beta-arrestins, whereas both isoforms are capable of supporting receptor desensitization and down-regulation. ..
  9. Attramadal H, Arriza J, Aoki C, Dawson T, Codina J, Kwatra M, et al. Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. J Biol Chem. 1992;267:17882-90 pubmed
    ..Furthermore, immunoelectron microscopy shows that the beta-arrestins are appropriately situated at postsynaptic sites to act in concert with beta ARK to regulate G protein-coupled neurotransmitter receptors. ..

More Information


  1. Girnita L, Shenoy S, Sehat B, Vasilcanu R, Girnita A, Lefkowitz R, 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;280:24412-9 pubmed
    ..To our knowledge this is the first study demonstrating a defined molecular role of beta-arrestin with direct relevance to cell growth and cancer. ..
  2. Hennenberg M, Trebicka J, Biecker E, Schepke M, Sauerbruch T, Heller J. Vascular dysfunction in human and rat cirrhosis: role of receptor-desensitizing and calcium-sensitizing proteins. Hepatology. 2007;45:495-506 pubmed
    ..Our data suggest that in cirrhosis-induced vasodilation, the AT1-R is desensitized by GRK-2 and beta-arrestin-2 and that changed patterns of phosphorylated Ca(2+) sensitizing proteins decrease Ca(2+) sensitivity. ..
  3. Ahn S, Nelson C, Garrison T, Miller W, Lefkowitz R. Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference. Proc Natl Acad Sci U S A. 2003;100:1740-4 pubmed
    ..This approach should allow discovery of novel signaling and regulatory roles for the beta-arrestins in many seven-membrane-spanning receptor systems. ..
  4. Chen W, Kirkbride K, How T, Nelson C, Mo J, Frederick J, et al. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science. 2003;301:1394-7 pubmed
    ..Thus, the regulatory actions of beta-arrestins are broader than previously appreciated, extending to the TGF-beta receptor family as well. ..
  5. Morris G, Nelson C, Everitt D, Brighton P, Standen N, Challiss R, et al. G protein-coupled receptor kinase 2 and arrestin2 regulate arterial smooth muscle P2Y-purinoceptor signalling. Cardiovasc Res. 2011;89:193-203 pubmed publisher
  6. Hennenberg M, Trebicka J, Kohistani A, Heller J, Sauerbruch T. Vascular hyporesponsiveness to angiotensin II in rats with CCl(4)-induced liver cirrhosis. Eur J Clin Invest. 2009;39:906-13 pubmed publisher
    ..Vascular hyporesponsiveness to angiotensin II in CCl(4) rats is due to enhanced interaction of the AT(1) receptor with beta-arrestin-2 and consecutively changed receptor function. ..
  7. Bohn L, Lefkowitz R, Gainetdinov R, Peppel K, Caron M, Lin F. Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science. 1999;286:2495-8 pubmed
    ..Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence. ..
  8. Boularan C, Scott M, Bourougaa K, Bellal M, Esteve E, Thuret A, et al. beta-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53. Proc Natl Acad Sci U S A. 2007;104:18061-6 pubmed
    ..These observations suggest that the intracellular concentration of beta-arr2 oligomers might control cell survival and proliferation. ..
  9. Yu M, Su L, 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 pubmed publisher
    ..Our findings identify a previously unknown mechanism by which the inhibitory signaling in NK cells is regulated. ..
  10. Li S, Guan J, Ge M, Huang P, Lin Y, Gan X. Intestinal mucosal injury induced by tryptase-activated protease-activated receptor 2 requires β-arrestin-2 in vitro. Mol Med Rep. 2015;12:7181-7 pubmed publisher
    ..These data indicate that tryptase may directly damage IEC‑6 cells via PAR-2 and the downstream activation of ERK, and demonstrate that the signaling pathway requires β-arrestin-2. ..
  11. Nakaya M, Chikura S, Watari K, Mizuno N, Mochinaga K, Mangmool S, et al. Induction of cardiac fibrosis by ?-blocker in G protein-independent and G protein-coupled receptor kinase 5/?-arrestin2-dependent Signaling pathways. J Biol Chem. 2012;287:35669-77 pubmed publisher
    ..This study demonstrates the physiological importance of biased agonism, and suggests that G protein-independent and ?-arrestin-dependent signaling is a reason for the diversity of the effectiveness of ?-blockers. ..
  12. Golan M, Schreiber G, Avissar S. Antidepressants increase ?-arrestin 2 ubiquitinylation and degradation by the proteasomal pathway in C6 rat glioma cells. J Pharmacol Exp Ther. 2010;332:970-6 pubmed publisher
  13. Xie D, Li S, Li L, Chang X, Xi T, Yang X, et al. Beta-arrestin2 is involved in the increase of distal colonic contraction in diabetic rats. Regul Pept. 2013;185:29-33 pubmed publisher
    ..The expression level of ?-arrestin2 protein in the colon was higher in diabetic rats than in normal rats. These results suggest that ?-arrestin2 is involved in the increase of distal colonic contraction in diabetic rats. ..
  14. Wang Y, Jin L, Song Y, Zhang M, Shan D, Liu Y, et al. ?-arrestin 2 mediates cardiac ischemia-reperfusion injury via inhibiting GPCR-independent cell survival signalling. Cardiovasc Res. 2017;113:1615-1626 pubmed publisher
    ..The expression of ?-arrestin 2 (Arrb2), but not ?-arrestin 1 (Arrb1), is upregulated in rat hearts subjected to I/R injury, or in cultured neonatal rat ..
  15. Liu H, Tian Y, Ji B, Lu H, Xin Q, Jiang Y, et al. Heterodimerization of the kappa opioid receptor and neurotensin receptor 1 contributes to a novel ?-arrestin-2-biased pathway. Biochim Biophys Acta. 2016;1863:2719-2738 pubmed publisher
  16. Hauger R, Risbrough V, Brauns O, Dautzenberg F. Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets. CNS Neurol Disord Drug Targets. 2006;5:453-79 pubmed
    ..If it is confirmed that the CRF(2) receptor contributes importantly to anxiety and depression, the development of small molecule CRF(2) receptor antagonists would be therapeutically useful. ..
  17. Tang L, Ni W, Cai M, Ding H, Liu S, Zhang S. Renoprotective effects of berberine and its potential effect on the expression of β-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats. J Diabetes. 2016;8:693-700 pubmed publisher
    ..Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney. ..
  18. Vilardaga J, Romero G, Friedman P, Gardella T. Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm. Cell Mol Life Sci. 2011;68:1-13 pubmed publisher
  19. Khan M, Devaraj H, Devaraj N. Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats. Toxicol Appl Pharmacol. 2011;251:85-94 pubmed publisher
    ..These findings suggest that chrysin exerts global hepato-protective effect and its chemopreventive activity is associated with p53-mediated apoptosis during early hepatocarcinogenesis. ..
  20. Pang Y, Zhu H, Xu J, Yang L, Liu L, Li J. ?-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling. Exp Cell Res. 2017;360:199-204 pubmed publisher
    ..In conclusion, we demonstrated that ?-arrestin-2 has a crucial role in irisin induced glucose metabolism in T2DM by regulating the p38 MAPK signaling. This might present a novel therapeutic target of treatment for human diabetes. ..
  21. Xiao K, Shenoy S, Nobles K, Lefkowitz R. Activation-dependent conformational changes in {beta}-arrestin 2. J Biol Chem. 2004;279:55744-53 pubmed
  22. Kyoi S, Otani H, Sumida T, Okada T, Osako M, Imamura H, et al. Loss of intracellular dystrophin: a potential mechanism for myocardial reperfusion injury. Circ J. 2003;67:725-7 pubmed
    ..Upon withdrawal of BDM, however, EB accumulated in dystrophin-depleted cardiomyocytes. Loss of sarcolemmal dystrophin may be involved in the mechanism of contractile force-induced reperfusion injury. ..
  23. Neuhaus E, Mashukova A, Barbour J, Wolters D, Hatt H. Novel function of beta-arrestin2 in the nucleus of mature spermatozoa. J Cell Sci. 2006;119:3047-56 pubmed
    ..Analysis of the interaction partners of beta-arrestin2 indicates that odorant receptor signaling in spermatozoa may be important for the regulation of gene expression during the early processes of fertilization. ..
  24. Chang F, Liu J, Fu H, Wang J, Li F, Yue H, et al. GSK-3β promotes PA-induced apoptosis through changing β-arrestin 2 nucleus location in H9c2 cardiomyocytes. Apoptosis. 2016;21:1045-55 pubmed publisher
    ..LiCl inhibits PA-induced cardiomyocyte apoptosis, which might provide novel therapeutic for cardiovascular diseases induced by metabolic syndrome. ..
  25. Gao H, Sun Y, Wu Y, Luan B, Wang Y, Qu B, et al. Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways. Mol Cell. 2004;14:303-17 pubmed
    ..Taken together, the current study may present a novel mechanism for regulation of the immune system by the sympathetic nervous system. ..
  26. Thomsen A, Hvidtfeldt M, Brauner Osborne H. Biased agonism of the calcium-sensing receptor. Cell Calcium. 2012;51:107-16 pubmed publisher
    ..In conclusion, the results of this study indicate that several active conformations of CaSR, stabilized by different molecules, exist, which affect intracellular signaling distinctly. ..
  27. Dent M, Tappia P, Dhalla N. Gender related alterations of ?-adrenoceptor mechanisms in heart failure due to arteriovenous fistula. J Cell Physiol. 2012;227:3080-7 pubmed publisher
    ..Furthermore, estrogen appears to play an important role in the upregulation of ?-AR mechanisms and the maintenance of cardiac function in AV-shunt females. ..
  28. Ahmed M, Zhan X, Song X, Kook S, Gurevich V, Gurevich E. Ubiquitin ligase parkin promotes Mdm2-arrestin interaction but inhibits arrestin ubiquitination. Biochemistry. 2011;50:3749-63 pubmed publisher
    ..Parkin binding to arrestins along with its effects on arrestin interaction with Mdm2 and ubiquitination is a novel function of this protein with implications for Parkinson's disease pathology. ..
  29. Wang Q, Zhang L, Wu H, Wei W. The expression change of ?-arrestins in fibroblast-like synoviocytes from rats with collagen-induced arthritis and the effect of total glucosides of paeony. J Ethnopharmacol. 2011;133:511-6 pubmed publisher
  30. Gurevich E, Benovic J, Gurevich V. Arrestin2 and arrestin3 are differentially expressed in the rat brain during postnatal development. Neuroscience. 2002;109:421-36 pubmed
    ..Thus, the response of receptors to specific drugs stimulating or blocking these receptors may depend on complement of arrestins in their target cells. ..
  31. Bjork K, Rimondini R, Hansson A, Terasmaa A, Hyytia P, Heilig M, et al. Modulation of voluntary ethanol consumption by beta-arrestin 2. FASEB J. 2008;22:2552-60 pubmed publisher
    ..We identified elevated expression of the beta-arrestin 2 gene (Arrb2) in the striatum and the hippocampus of ethanol-preferring AA rats compared to their nonpreferring counterpart ANA ..
  32. Stanasila L, Abuin L, Dey J, Cotecchia S. Different internalization properties of the alpha1a- and alpha1b-adrenergic receptor subtypes: the potential role of receptor interaction with beta-arrestins and AP50. Mol Pharmacol. 2008;74:562-73 pubmed publisher
  33. Lee M, Appleton K, Strungs E, Kwon J, Morinelli T, Peterson Y, et al. The conformational signature of β-arrestin2 predicts its trafficking and signalling functions. Nature. 2016;531:665-8 pubmed publisher
    ..This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function. ..
  34. Wang Q, Zhao J, Brady A, Feng J, Allen P, Lefkowitz R, et al. Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors. Science. 2004;304:1940-4 pubmed
    ..The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses. ..
  35. Li X, Baillie G, Houslay M. Mdm2 directs the ubiquitination of beta-arrestin-sequestered cAMP phosphodiesterase-4D5. J Biol Chem. 2009;284:16170-82 pubmed publisher
  36. Wang B, Yang Y, Abou Samra A, Friedman P. NHERF1 regulates parathyroid hormone receptor desensitization: interference with beta-arrestin binding. Mol Pharmacol. 2009;75:1189-97 pubmed publisher
    ..NHERF1 inhibited beta-arrestin2 binding to wtPTH1R but had no effect on beta-arrestin2 association with pdPTH1R. Such an effect may protect against PTH resistance or PTH1R down-regulation in cells harboring NHERF1. ..
  37. Mancini A, Bertrand G, Vivot K, Carpentier Ã, Tremblay C, Ghislain J, et al. β-Arrestin Recruitment and Biased Agonism at Free Fatty Acid Receptor 1. J Biol Chem. 2015;290:21131-40 pubmed publisher
    ..These observations expose previously unrecognized complexity for GPR40 signal transduction and may guide the development of biased agonists showing improved clinical profile in type 2 diabetes. ..
  38. Liu C, Huang Y, Zhang J, Xu Y, Wu C. Effect of carvedilol on cardiac dysfunction 4 days after myocardial infarction in rats: role of toll-like receptor 4 and ?-arrestin 2. Eur Rev Med Pharmacol Sci. 2013;17:2103-10 pubmed
    ..This beneficial effect may be attributed to inhibit the expression of NF-?B and TLR4, but induce the expression of ?-arrestin 2 in the infarct region of the myocardium, which would suppress inflammation. ..
  39. Cottrell G, Padilla B, Amadesi S, Poole D, Murphy J, Hardt M, et al. Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling. J Biol Chem. 2009;284:22411-25 pubmed publisher
    ..We propose that agonist availability in endosomes, here regulated by ECE-1, controls beta-arrestin-dependent signaling of endocytosed GPCRs. ..
  40. Bychkov E, Zurkovsky L, Garret M, Ahmed M, Gurevich E. Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum. PLoS ONE. 2012;7:e48912 pubmed publisher
    ..These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling. ..
  41. Ogasawara J, Sanpei M, Rahman N, Sakurai T, Kizaki T, Hitomi Y, et al. Beta-adrenergic receptor trafficking by exercise in rat adipocytes: roles of G-protein-coupled receptor kinase-2, beta-arrestin-2, and the ubiquitin-proteasome pathway. FASEB J. 2006;20:350-2 pubmed
    ..However, the decreased protein expression of beta2-AR at 24 h might be due to some change occurring at the translational levels. ..
  42. Monasky M, Taglieri D, Henze M, Warren C, Utter M, Soergel D, et al. The ?-arrestin-biased ligand TRV120023 inhibits angiotensin II-induced cardiac hypertrophy while preserving enhanced myofilament response to calcium. Am J Physiol Heart Circ Physiol. 2013;305:H856-66 pubmed publisher
    ..Selective activation of ?-arrestin-dependent pathways may provide advantages over conventional AT1R blockers. ..
  43. Morinelli T, Lee M, Kendall R, Luttrell L, Walker L, Ullian M. Angiotensin II activates NF-?B through AT1A receptor recruitment of ?-arrestin in cultured rat vascular smooth muscle cells. Am J Physiol Cell Physiol. 2013;304:C1176-86 pubmed publisher
  44. Zhao J, Feng Y, Yan H, Chen Y, Wang J, CHUA B, et al. ?-arrestin2/miR-155/GSK3? regulates transition of 5'-azacytizine-induced Sca-1-positive cells to cardiomyocytes. J Cell Mol Med. 2014;18:1562-70 pubmed publisher
    ..The ?-arrestin2/miR-155/GSK3? pathway may be a new mechanism with implications for treatment of heart disease. ..
  45. Yun Y, Kim D, Seo M, Kim K, Chung K. Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry. Biochem Biophys Res Commun. 2015;457:50-7 pubmed publisher
    ..The conformational differences between β-arrestin1 and β-arrestin2 in both the basal and pre-activated states might determine their different receptor selectivities and different cellular functions. ..
  46. Por E, Gomez R, Akopian A, Jeske N. Phosphorylation regulates TRPV1 association with ?-arrestin-2. Biochem J. 2013;451:101-9 pubmed publisher
    ..Taken together, the findings of the present study suggest that phosphorylation controls the association of TRPV1 with ?-arrestin-2. ..
  47. Canals M, Scholten D, de Munnik S, Han M, Smit M, Leurs R. Ubiquitination of CXCR7 controls receptor trafficking. PLoS ONE. 2012;7:e34192 pubmed publisher
    ..Together these data demonstrate the differential regulation of CXCR7 compared to the related CXCR3 and CXCR4 receptors, and highlight the importance of understanding the molecular determinants responsible for this process. ..
  48. Zimmerman B, Simaan M, Akoume M, Houri N, Chevallier S, Séguéla P, et al. Role of ßarrestins in bradykinin B2 receptor-mediated signalling. Cell Signal. 2011;23:648-59 pubmed publisher
    ..These results highlight ßarrestin's crucial role in the maintenance of proper B2R signalling. ..
  49. Molteni R, Crespo C, Feigelson S, Moser C, Fabbri M, Grabovsky V, et al. Beta-arrestin 2 is required for the induction and strengthening of integrin-mediated leukocyte adhesion during CXCR2-driven extravasation. Blood. 2009;114:1073-82 pubmed publisher
    ..Thus, receptor-induced Galpha(i) and beta-arrestins act sequentially and in spatially distinct compartments to promote optimal KC-induced integrin-dependent adhesion during leukocyte extravasation. ..
  50. Scheggi S, Ferrari A, Pelliccia T, Devoto P, De Montis M, Gambarana C. Fasting biases ?-opioid receptors toward ?-arrestin2-dependent signaling in the accumbens shell. Neuroscience. 2017;352:19-29 pubmed publisher
    ..These results show the ?-arrestin2-dependent prevalence of dopamine D1 receptor signaling in response to acute morphine or sucrose consumption elicited by food deprivation in rats. ..
  51. Khoury E, Nikolajev L, Simaan M, Namkung Y, Laporte S. Differential regulation of endosomal GPCR/?-arrestin complexes and trafficking by MAPK. J Biol Chem. 2014;289:23302-17 pubmed publisher
    ..Our findings unveil a novel subtype specific mode of MAPK-dependent regulation of ?-arrestins in intracellular trafficking and signaling of GPCRs, and suggest differential endosomal receptor/?-arrestin-2 signaling roles among species. ..
  52. Beaulieu J, Sotnikova T, Marion S, Lefkowitz R, Gainetdinov R, Caron M. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell. 2005;122:261-73 pubmed
  53. Komori N, Cain S, Roch J, Miller K, Matsumoto H. Differential expression of alternative splice variants of beta-arrestin-1 and -2 in rat central nervous system and peripheral tissues. Eur J Neurosci. 1998;10:2607-16 pubmed