Gene Symbol: Arrb1
Description: arrestin, beta 1
Alias: BARRES, beta-arrestin-1
Species: rat
Products:     Arrb1

Top Publications

  1. 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. ..
  2. 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. ..
  3. Dominguez R, Hu E, Zhou M, Baudry M. 17beta-estradiol-mediated neuroprotection and ERK activation require a pertussis toxin-sensitive mechanism involving GRK2 and beta-arrestin-1. J Neurosci. 2009;29:4228-38 pubmed publisher
    ..These results demonstrate that E2-mediated neuroprotection and ERK activation involve ERalpha activation of G-protein- and beta-arrestin-mediated mechanisms...
  4. Orsini M, Parent J, Mundell S, Marchese A, Benovic J. 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;274:31076-86 pubmed
  5. 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
  6. DeWire S, Kim J, Whalen E, Ahn S, Chen M, Lefkowitz R. Beta-arrestin-mediated signaling regulates protein synthesis. J Biol Chem. 2008;283:10611-20 pubmed publisher
    ..This novel demonstration that beta-arrestins regulate protein synthesis reveals that the spectrum of beta-arrestin-mediated signaling events is broader than previously imagined. ..
  7. 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. ..
  8. Nobles K, Guan Z, Xiao K, Oas T, Lefkowitz R. The active conformation of beta-arrestin1: direct evidence for the phosphate sensor in the N-domain and conformational differences in the active states of beta-arrestins1 and -2. J Biol Chem. 2007;282:21370-81 pubmed
    ..This study represents the first direct evidence that the "receptor-bound" conformations of beta-arrestins1 and 2 are different. ..
  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. Ge L, Ly Y, Hollenberg M, DeFea K. A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem. 2003;278:34418-26 pubmed
  2. 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
  3. Komori N, Neal J, Cain S, Logan J, Wirsig C, Miller K. Presence of beta-arrestin-1 immunoreactivity in the cutaneous nerve fibers of rat glabrous skin. Brain Res. 2003;988:121-9 pubmed
    ..Our observations thus indicate that betaArr1 may be involved in modulation of specific tactile stimulation from the skin in addition to nociception. ..
  4. Vinge L, Øie E, Andersson Y, Grøgaard H, Andersen G, Attramadal H. Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats. Am J Physiol Heart Circ Physiol. 2001;281:H2490-9 pubmed
    ..Conversely, the cellular distribution of GRK3 and GRK5 implicates these isoforms as putative regulators of cardiac myocyte function...
  5. 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
  6. 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. ..
  7. Lyubarsky A, Lem J, Chen J, Falsini B, Iannaccone A, Pugh E. Functionally rodless mice: transgenic models for the investigation of cone function in retinal disease and therapy. Vision Res. 2002;42:401-15 pubmed
    ..The desensitizing effect of the 530 nm background on UV-pigment driven responses provides new evidence in support of the hypothesis of functional co-expression of the M-pigment in cones expressing primarily the UV-pigment. ..
  8. Sood R, Ritov G, Richter Levin G, Barki Harrington L. Selective increase in the association of the ?2 adrenergic receptor, ? Arrestin-1 and p53 with Mdm2 in the ventral hippocampus one month after underwater trauma. Behav Brain Res. 2013;240:26-8 pubmed publisher
    ..Our results provide support for the idea that stress-related events may result in biochemical changes restricted to the ventral 'emotion-related' parts of the hippocampus. ..
  9. 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. ..
  10. Zhou P, Fan H, Hu H, Tang Q, Liu X, Zhang L, et al. Role of DOR-?-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis. J Huazhong Univ Sci Technolog Med Sci. 2014;34:815-820 pubmed publisher
    ..Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-?-arrestin1-Bcl-2 signal transduction pathway. ..
  11. 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
  12. Jia J, Zeng X, Zhou X, Li Y, Bai J. The induction of thioredoxin-1 by epinephrine withdraws stress via interaction with β-arrestin-1. Cell Cycle. 2014;13:3121-31 pubmed publisher
    ..Taken together, our data suggest that Trx-1/β-arrestin-1 interaction may represent a novel endogenous mechanism on protecting against stress. ..
  13. 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 pubmed publisher
    ..Such signaling mechanism may serve as a prototype to generate new therapeutic GLP-1R ligands. ..
  14. Barnes W, Reiter E, Violin J, Ren X, Milligan G, Lefkowitz R. beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. J Biol Chem. 2005;280:8041-50 pubmed
  15. Perry S, Baillie G, Kohout T, McPhee I, Magiera M, Ang K, et al. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science. 2002;298:834-6 pubmed
  16. 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
  17. Marion S, Kara E, Crepieux P, Piketty V, Martinat N, Guillou F, et al. G protein-coupled receptor kinase 2 and beta-arrestins are recruited to FSH receptor in stimulated rat primary Sertoli cells. J Endocrinol. 2006;190:341-50 pubmed
    ..This FSH-R interaction with beta-arrestins was sustained for up to 30 min. In conclusion, our data strongly suggest that the GRK/beta-arrestin machinery plays a physiologically relevant role in the regulation of the FSH signaling. ..
  18. Zakrzewicz A, Krasteva G, Wilhelm J, Dietrich H, Wilker S, Padberg W, et al. Reduced expression of arrestin beta 2 by graft monocytes during acute rejection of rat kidneys. Immunobiology. 2011;216:854-61 pubmed publisher
    ..Intravascular mononuclear graft leukocytes were isolated 4 days after kidney transplantation. ARRB1 and ARRB2 mRNA expression was reduced in blood leukocytes from allografts undergoing acute rejection, whereas on ..
  19. Zhu W, Tilley D, Myers V, Coleman R, Feldman A. Arginine vasopressin enhances cell survival via a G protein-coupled receptor kinase 2/?-arrestin1/extracellular-regulated kinase 1/2-dependent pathway in H9c2 cells. Mol Pharmacol. 2013;84:227-35 pubmed publisher
  20. Zoudilova M, Kumar P, Ge L, Wang P, Bokoch G, DeFea K. Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem. 2007;282:20634-46 pubmed
    ..These findings identify cofilin as a novel target of beta-arrestin-dependent scaffolding and suggest that many PAR-2-induced processes may be independent of Galpha(q/11) protein coupling. ..
  21. MacKenzie K, Wallace D, Hill E, Anthony D, Henderson D, Houslay D, et al. Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation. Biochem J. 2011;435:755-69 pubmed publisher
    ..Long PDE4 isoforms thus provide a novel node for cross-talk between the cAMP and p38 MAPK signalling systems at the level of MK2. ..
  22. Venkatesha R, Ahamed J, Nuesch C, Zaidi A, Ali H. Platelet-activating factor-induced chemokine gene expression requires NF-kappaB activation and Ca2+/calcineurin signaling pathways. Inhibition by receptor phosphorylation and beta-arrestin recruitment. J Biol Chem. 2004;279:44606-12 pubmed
    ..However, receptor phosphorylation and beta-arrestin recruitment inhibit CCL2 production by blocking both NF-kappaB activation and Ca2+/calcineurin-dependent signaling pathways. ..
  23. McDonald P, Cote N, Lin F, Premont R, Pitcher J, Lefkowitz R. Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. J Biol Chem. 1999;274:10677-80 pubmed
  24. Beaulieu J, Gainetdinov R. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011;63:182-217 pubmed publisher
  25. 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;7:139-47 pubmed
    ..Thus, beta-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling. ..
  26. Wong A, Abrams M, Micevych P. β-arrestin regulates estradiol membrane-initiated signaling in hypothalamic neurons. PLoS ONE. 2015;10:e0120530 pubmed publisher
    ..arrestin-1 (Arrb1) was found in the ARH and in N-38 neurons...
  27. Barki Harrington L, Rockman H. Beta-arrestins: multifunctional cellular mediators. Physiology (Bethesda). 2008;23:17-22 pubmed publisher
    ..This review explores the many functions of beta-arrestins, with an emphasis on their recently identified role as regulators of receptor signaling. ..
  28. Kendall R, Lee M, Pleasant D, Robinson K, Kuppuswamy D, McDermott P, et al. Arrestin-dependent angiotensin AT1 receptor signaling regulates Akt and mTor-mediated protein synthesis. J Biol Chem. 2014;289:26155-66 pubmed publisher
    ..These results suggest that in vivo, arrestin pathway-selective AT1 receptor agonists may promote cell growth or hypertrophy through arrestin-mediated mechanisms despite their antagonism of G protein signaling. ..
  29. Das M, Ghosh M, Das S. Thyroid Hormone-Induced Differentiation of Astrocytes is Associated with Transcriptional Upregulation of β-arrestin-1 and β-adrenergic Receptor-Mediated Endosomal Signaling. Mol Neurobiol. 2016;53:5178-90 pubmed publisher
    ..Observations suggest that TH upregulate β-arrestin-1 in astrocytes to facilitate endocytosis of β2-AR, required for endosomal ERK activation to drive the differentiation process. ..
  30. Lee C, Bhatt S, Shukla A, Desnoyer R, Yadav S, Kim M, et al. Site-specific cleavage of G protein-coupled receptor-engaged beta-arrestin. Influence of the AT1 receptor conformation on scissile site selection. J Biol Chem. 2008;283:21612-20 pubmed publisher
    ..Our findings suggest that beta-arrestin cleavage upon AT(1)R stimulation is a part of the unraveling beta-arrestin-mediated G protein-coupled receptor signaling diversity. ..
  31. Mishra S, Keyel P, Edeling M, Dupin A, Owen D, Traub L. Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein. J Biol Chem. 2005;280:19270-80 pubmed
    ..We suggested that biased beta subunit engagement by ARH and the only other beta2 appendage selective adaptor, beta-arrestin, promotes efficient incorporation of this mechanistically distinct subset of CLASPs into clathrin-coated buds. ..
  32. Dalle S, Imamura T, Rose D, Worrall D, Ugi S, Hupfeld C, et al. Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating beta-arrestin-1. Mol Cell Biol. 2002;22:6272-85 pubmed
  33. Shukla A, Kim J, Ahn S, Xiao K, Shenoy S, Liedtke W, et al. Arresting a transient receptor potential (TRP) channel: beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4. J Biol Chem. 2010;285:30115-25 pubmed publisher
    ..Thus, our data provide the first evidence of a functional link between ?-arrestins and TRPV4 and uncovers an entirely novel mechanism to maintain appropriate intracellular Ca(2+) concentration to avoid excessive Ca(2+) signaling. ..
  34. Puca L, Chastagner P, Meas Yedid V, Israel A, Brou C. ?-arrestin 1 (ARRDC1) and ?-arrestins cooperate to mediate Notch degradation in mammals. J Cell Sci. 2013;126:4457-68 pubmed publisher
    ..Our data show for the first time that ARRDC1 and ?-arrestins heterodimerize and cooperate in the same complex to promote non-activated Notch receptor degradation, thus acting as negative regulators of Notch signaling. ..
  35. Shukla A, Manglik A, Kruse A, Xiao K, Reis R, Tseng W, et al. Structure of active ?-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide. Nature. 2013;497:137-41 pubmed publisher
    ..These results reveal, at high resolution, a receptor-interacting interface on ?-arrestin, and they indicate a potentially general molecular mechanism for activation of these multifunctional signalling and regulatory proteins. ..
  36. Li B, Wang C, Zhou Z, Zhao J, Pei G. ?-Arrestin-1 directly interacts with G?s and regulates its function. FEBS Lett. 2013;587:410-6 pubmed publisher
    ..Arrestin-1 L33K mutant shows reduced interaction with G?(s) and has no detectable effects on G?(s) function. Our study thus reveals a direct crosstalk of ?-arrestin-1 with G?(s). ..
  37. Dorn G. GRK mythology: G-protein receptor kinases in cardiovascular disease. J Mol Med (Berl). 2009;87:455-63 pubmed publisher
    ..Here, recent developments are reviewed, with an emphasis on novel GRK functions and signaling pathways. ..
  38. Hara M, Kovacs J, Whalen E, Rajagopal S, Strachan R, Grant W, et al. A stress response pathway regulates DNA damage through ?2-adrenoreceptors and ?-arrestin-1. Nature. 2011;477:349-53 pubmed publisher
    ..In mice and in human cell lines, ?-arrestin-1 (ARRB1), activated via ?(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding ..
  39. Usui I, Imamura T, Huang J, Satoh H, Shenoy S, Lefkowitz R, et al. beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1. Mol Cell Biol. 2004;24:8929-37 pubmed
  40. Lymperopoulos A, Rengo G, Zincarelli C, Kim J, Koch W. 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;57:356-65 pubmed publisher
    ..Adrenal ?arr1 inhibition, either directly or with AT?R "biased" antagonists that prevent receptor-?arr1 coupling, might be of therapeutic value for curbing HF-exacerbating hyperaldosteronism. ..
  41. Liao Y, Fan H, Chen X. [Pathogenetic mechanism of beta-arrestin1 in experimental colitis of rats and intervention effects of oxymatrine]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010;30:1067-72 pubmed
    ..Oxymatrine can intervene the signal transduction, which may be one of the mechanisms of oxymatrine in attenuating colitis in rats. ..
  42. Chen W, Hu L, Semenov M, Yanagawa S, Kikuchi A, Lefkowitz R, et al. beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. Proc Natl Acad Sci U S A. 2001;98:14889-94 pubmed
  43. Shenoy S, Lefkowitz R. Angiotensin II-stimulated signaling through G proteins and beta-arrestin. Sci STKE. 2005;2005:cm14 pubmed
  44. Marion S, Fralish G, Laporte S, Caron M, Barak L. N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins. J Biol Chem. 2007;282:18937-44 pubmed
    ..Additionally, these naturally occurring variations in beta-arrestins may also differentially regulate the composition of the signaling complexes organized on the receptor. ..
  45. Kroeger K, Hanyaloglu A, Seeber R, Miles L, Eidne K. Constitutive and agonist-dependent homo-oligomerization of the thyrotropin-releasing hormone receptor. Detection in living cells using bioluminescence resonance energy transfer. J Biol Chem. 2001;276:12736-43 pubmed
    ..This study supports the usefulness of BRET as a powerful tool for studying GPCR aggregations and receptor/protein interactions in general and presents evidence that the functioning unit of TRHRs exists as homomeric complexes. ..
  46. Iacovelli L, Salvatore L, Capobianco L, Picascia A, Barletta E, Storto M, et al. Role of G protein-coupled receptor kinase 4 and beta-arrestin 1 in agonist-stimulated metabotropic glutamate receptor 1 internalization and activation of mitogen-activated protein kinases. J Biol Chem. 2003;278:12433-42 pubmed
    ..We conclude that GRK2 and GRK4 regulate the mGlu(1) receptor by different mechanisms and that beta-arrestin is directly involved in glutamate-stimulated MAP kinase activation by acting as a signaling molecule. ..
  47. 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
    The two widely coexpressed isoforms of beta-arrestin (termed beta arrestin 1 and 2) are highly similar in amino acid sequence...
  48. Wang W, Wu X, Jia L, Zhang H, Cai F, Mao H, et al. Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis. Neuroscience. 2016;313:199-212 pubmed publisher
    ..These results suggested that β-arr1 and 2 may differently modulate mGluR7 signaling in developmental sevoflurane neurotoxicity. This study also reveals a β-arr-biased agonism at GPCRs (e.g. mGluR7). ..
  49. Pi M, Oakley R, Gesty Palmer D, Cruickshank R, Spurney R, Luttrell L, et al. Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization. Mol Endocrinol. 2005;19:1078-87 pubmed
    ..We conclude that GRKs and beta-arrestins play key roles in regulating CASR responsiveness in parathyroid glands. ..
  50. Flores Otero J, Ahn K, Delgado Peraza F, Mackie K, Kendall D, Yudowski G. Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1. Nat Commun. 2014;5:4589 pubmed publisher
    ..These studies reveal how receptor activation translates into ?-arrestin signalling and identify a mechanism to control this pathway. ..
  51. Schmidlin F, Roosterman D, Bunnett N. The third intracellular loop and carboxyl tail of neurokinin 1 and 3 receptors determine interactions with beta-arrestins. Am J Physiol Cell Physiol. 2003;285:C945-58 pubmed
    ..Thus loop 3 and the COOH tail specify colocalization of the NK1R with beta-arrestin 1 and determine the rate of resensitization. ..
  52. Lombardi M, van den Tweel E, Kavelaars A, Groenendaal F, van Bel F, Heijnen C. Hypoxia/ischemia modulates G protein-coupled receptor kinase 2 and beta-arrestin-1 levels in the neonatal rat brain. Stroke. 2004;35:981-6 pubmed
    ..We hypothesize that these changes result in supersensitization of multiple GPCRs and might therefore contribute to HI-induced brain damage. ..