• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Nov 1, 2003; 375(Pt 3): 503–515.
PMCID: PMC1223736

Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling.


Beta-arrestins are cytosolic proteins that bind to activated and phosphorylated G-protein-coupled receptors [7MSRs (seven-membrane-spanning receptors)] and uncouple them from G-protein-mediated second messenger signalling pathways. The binding of beta-arrestins to 7MSRs also leads to new signals via activation of MAPKs (mitogen-activated protein kinases) such as JNK3 (c-Jun N-terminal kinase 3), ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38 MAPKs. By binding to endocytic proteins [clathrin, AP2 (adapter protein 2), NSF (N -ethylmaleimide-sensitive fusion protein) and ARF6 (ADP-ribosylation factor 6)], beta-arrestins also serve as adapters to link the receptors to the cellular trafficking machinery. Agonist-promoted ubiquitination of beta-arrestins is a prerequisite for their role in receptor internalization, as well as a determinant of the differing trafficking patterns of distinct classes of receptors. Recently, beta-arrestins have also been implicated as playing novel roles in cellular chemotaxis and apoptosis. By virtue of their ability to bind, in a stimulus-dependent fashion, to 7MSRs as well as to different classes of cellular proteins, beta-arrestins serve as versatile adapter proteins that regulate the signalling and trafficking of the receptors.

Full Text

The Full Text of this article is available as a PDF (326K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Pierce Kristen L, Premont Richard T, Lefkowitz Robert J. Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 2002 Sep;3(9):639–650. [PubMed]
  • Stadel JM, Nambi P, Shorr RG, Sawyer DF, Caron MG, Lefkowitz RJ. Phosphorylation of the beta-adrenergic receptor accompanies catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase. Trans Assoc Am Physicians. 1983;96:137–145. [PubMed]
  • Sibley DR, Peters JR, Nambi P, Caron MG, Lefkowitz RJ. Desensitization of turkey erythrocyte adenylate cyclase. Beta-adrenergic receptor phosphorylation is correlated with attenuation of adenylate cyclase activity. J Biol Chem. 1984 Aug 10;259(15):9742–9749. [PubMed]
  • Lefkowitz RJ. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J Biol Chem. 1998 Jul 24;273(30):18677–18680. [PubMed]
  • Benovic JL, Strasser RH, Caron MG, Lefkowitz RJ. Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci U S A. 1986 May;83(9):2797–2801. [PMC free article] [PubMed]
  • Carman CV, Parent JL, Day PW, Pronin AN, Sternweis PM, Wedegaertner PB, Gilman AG, Benovic JL, Kozasa T. Selective regulation of Galpha(q/11) by an RGS domain in the G protein-coupled receptor kinase, GRK2. J Biol Chem. 1999 Nov 26;274(48):34483–34492. [PubMed]
  • Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ. Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. Science. 1992 Aug 28;257(5074):1264–1267. [PubMed]
  • Stoffel RH, Randall RR, Premont RT, Lefkowitz RJ, Inglese J. Palmitoylation of G protein-coupled receptor kinase, GRK6. Lipid modification diversity in the GRK family. J Biol Chem. 1994 Nov 11;269(45):27791–27794. [PubMed]
  • Pitcher JA, Fredericks ZL, Stone WC, Premont RT, Stoffel RH, Koch WJ, Lefkowitz RJ. Phosphatidylinositol 4,5-bisphosphate (PIP2)-enhanced G protein-coupled receptor kinase (GRK) activity. Location, structure, and regulation of the PIP2 binding site distinguishes the GRK subfamilies. J Biol Chem. 1996 Oct 4;271(40):24907–24913. [PubMed]
  • Pitcher JA, Freedman NJ, Lefkowitz RJ. G protein-coupled receptor kinases. Annu Rev Biochem. 1998;67:653–692. [PubMed]
  • Stoffel RH, Inglese J, Macrae AD, Lefkowitz RJ, Premont RT. Palmitoylation increases the kinase activity of the G protein-coupled receptor kinase, GRK6. Biochemistry. 1998 Nov 17;37(46):16053–16059. [PubMed]
  • Barak LS, Warabi K, Feng X, Caron MG, Kwatra MM. Real-time visualization of the cellular redistribution of G protein-coupled receptor kinase 2 and beta-arrestin 2 during homologous desensitization of the substance P receptor. J Biol Chem. 1999 Mar 12;274(11):7565–7569. [PubMed]
  • Cong M, Perry SJ, Lin FT, Fraser ID, Hu LA, Chen W, Pitcher JA, Scott JD, Lefkowitz RJ. Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. J Biol Chem. 2001 May 4;276(18):15192–15199. [PubMed]
  • Freedman NJ, Ament AS, Oppermann M, Stoffel RH, Exum ST, Lefkowitz RJ. Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor kinase specificity. J Biol Chem. 1997 Jul 11;272(28):17734–17743. [PubMed]
  • Dhami Gurpreet Kaur, Anborgh Pieter H, Dale Lianne B, Sterne-Marr Rachel, Ferguson Stephen S G. Phosphorylation-independent regulation of metabotropic glutamate receptor signaling by G protein-coupled receptor kinase 2. J Biol Chem. 2002 Jul 12;277(28):25266–25272. [PubMed]
  • Lodowski David T, Pitcher Julie A, Capel W Darrell, Lefkowitz Robert J, Tesmer John J G. Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma. Science. 2003 May 23;300(5623):1256–1262. [PubMed]
  • Benovic JL, Kühn H, Weyand I, Codina J, Caron MG, Lefkowitz RJ. Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc Natl Acad Sci U S A. 1987 Dec;84(24):8879–8882. [PMC free article] [PubMed]
  • Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science. 1990 Jun 22;248(4962):1547–1550. [PubMed]
  • 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. J Biol Chem. 1992 Sep 5;267(25):17882–17890. [PubMed]
  • Craft CM, Whitmore DH, Wiechmann AF. Cone arrestin identified by targeting expression of a functional family. J Biol Chem. 1994 Feb 11;269(6):4613–4619. [PubMed]
  • Gurevich VV, Richardson RM, Kim CM, Hosey MM, Benovic JL. Binding of wild type and chimeric arrestins to the m2 muscarinic cholinergic receptor. J Biol Chem. 1993 Aug 15;268(23):16879–16882. [PubMed]
  • Gurevich VV, Dion SB, Onorato JJ, Ptasienski J, Kim CM, Sterne-Marr R, Hosey MM, Benovic JL. Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors. J Biol Chem. 1995 Jan 13;270(2):720–731. [PubMed]
  • Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, Lin F, Kawakatsu H, Owada K, Luttrell DK, et al. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science. 1999 Jan 29;283(5402):655–661. [PubMed]
  • Min Le, Galet Colette, Ascoli Mario. The association of arrestin-3 with the human lutropin/choriogonadotropin receptor depends mostly on receptor activation rather than on receptor phosphorylation. J Biol Chem. 2002 Jan 4;277(1):702–710. [PubMed]
  • Qian H, Pipolo L, Thomas WG. Association of beta-Arrestin 1 with the type 1A angiotensin II receptor involves phosphorylation of the receptor carboxyl terminus and correlates with receptor internalization. Mol Endocrinol. 2001 Oct;15(10):1706–1719. [PubMed]
  • Shenoy Sudha K, Lefkowitz Robert J. Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J Biol Chem. 2003 Apr 18;278(16):14498–14506. [PubMed]
  • Barak LS, Ferguson SS, Zhang J, Caron MG. A beta-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation. J Biol Chem. 1997 Oct 31;272(44):27497–27500. [PubMed]
  • Pals-Rylaarsdam R, Gurevich VV, Lee KB, Ptasienski JA, Benovic JL, Hosey MM. Internalization of the m2 muscarinic acetylcholine receptor. Arrestin-independent and -dependent pathways. J Biol Chem. 1997 Sep 19;272(38):23682–23689. [PubMed]
  • Vishnivetskiy SA, Paz CL, Schubert C, Hirsch JA, Sigler PB, Gurevich VV. How does arrestin respond to the phosphorylated state of rhodopsin? J Biol Chem. 1999 Apr 23;274(17):11451–11454. [PubMed]
  • Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG. Association of beta-arrestin with G protein-coupled receptors during clathrin-mediated endocytosis dictates the profile of receptor resensitization. J Biol Chem. 1999 Nov 5;274(45):32248–32257. [PubMed]
  • Kovoor A, Celver J, Abdryashitov RI, Chavkin C, Gurevich VV. Targeted construction of phosphorylation-independent beta-arrestin mutants with constitutive activity in cells. J Biol Chem. 1999 Mar 12;274(11):6831–6834. [PubMed]
  • Lohse MJ, Andexinger S, Pitcher J, Trukawinski S, Codina J, Faure JP, Caron MG, Lefkowitz RJ. Receptor-specific desensitization with purified proteins. Kinase dependence and receptor specificity of beta-arrestin and arrestin in the beta 2-adrenergic receptor and rhodopsin systems. J Biol Chem. 1992 Apr 25;267(12):8558–8564. [PubMed]
  • Mukherjee S, Palczewski K, Gurevich V, Benovic JL, Banga JP, Hunzicker-Dunn M. A direct role for arrestins in desensitization of the luteinizing hormone/choriogonadotropin receptor in porcine ovarian follicular membranes. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):493–498. [PMC free article] [PubMed]
  • Ahn Seungkirl, Nelson Christopher D, Garrison Tiffany Runyan, Miller William E, Lefkowitz Robert J. Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1740–1744. [PMC free article] [PubMed]
  • Mundell SJ, Loudon RP, Benovic JL. Characterization of G protein-coupled receptor regulation in antisense mRNA-expressing cells with reduced arrestin levels. Biochemistry. 1999 Jul 6;38(27):8723–8732. [PubMed]
  • Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ. beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1601–1606. [PMC free article] [PubMed]
  • Paing May M, Stutts Amy B, Kohout Trudy A, Lefkowitz Robert J, Trejo JoAnn. beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation. J Biol Chem. 2002 Jan 11;277(2):1292–1300. [PubMed]
  • Perry Stephen J, Baillie George S, Kohout Trudy A, McPhee Ian, Magiera Maria M, Ang Kok Long, Miller William E, McLean Alison J, Conti Marco, Houslay Miles D, et al. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science. 2002 Oct 25;298(5594):834–836. [PubMed]
  • Conner DA, Mathier MA, Mortensen RM, Christe M, Vatner SF, Seidman CE, Seidman JG. beta-Arrestin1 knockout mice appear normal but demonstrate altered cardiac responses to beta-adrenergic stimulation. Circ Res. 1997 Dec;81(6):1021–1026. [PubMed]
  • Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT. Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science. 1999 Dec 24;286(5449):2495–2498. [PubMed]
  • Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature. 2000 Dec 7;408(6813):720–723. [PubMed]
  • Lefkowitz RJ, Pitcher J, Krueger K, Daaka Y. Mechanisms of beta-adrenergic receptor desensitization and resensitization. Adv Pharmacol. 1998;42:416–420. [PubMed]
  • Hausdorff WP, Campbell PT, Ostrowski J, Yu SS, Caron MG, Lefkowitz RJ. A small region of the beta-adrenergic receptor is selectively involved in its rapid regulation. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):2979–2983. [PMC free article] [PubMed]
  • Barak LS, Tiberi M, Freedman NJ, Kwatra MM, Lefkowitz RJ, Caron MG. A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration. J Biol Chem. 1994 Jan 28;269(4):2790–2795. [PubMed]
  • Ménard L, Ferguson SS, Barak LS, Bertrand L, Premont RT, Colapietro AM, Lefkowitz RJ, Caron MG. Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration. Biochemistry. 1996 Apr 2;35(13):4155–4160. [PubMed]
  • Claing Audrey, Laporte Stéphane A, Caron Marc G, Lefkowitz Robert J. Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and beta-arrestin proteins. Prog Neurobiol. 2002 Feb;66(2):61–79. [PubMed]
  • von Zastrow M, Kobilka BK. Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors. J Biol Chem. 1992 Feb 15;267(5):3530–3538. [PubMed]
  • Ferguson SS, Downey WE, 3rd, Colapietro AM, Barak LS, Ménard L, Caron MG. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science. 1996 Jan 19;271(5247):363–366. [PubMed]
  • Goodman OB, Jr, Krupnick JG, Santini F, Gurevich VV, Penn RB, Gagnon AW, Keen JH, Benovic JL. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor. Nature. 1996 Oct 3;383(6599):447–450. [PubMed]
  • Goodman OB, Jr, Krupnick JG, Gurevich VV, Benovic JL, Keen JH. Arrestin/clathrin interaction. Localization of the arrestin binding locus to the clathrin terminal domain. J Biol Chem. 1997 Jun 6;272(23):15017–15022. [PubMed]
  • Krupnick JG, Goodman OB, Jr, Keen JH, Benovic JL. Arrestin/clathrin interaction. Localization of the clathrin binding domain of nonvisual arrestins to the carboxy terminus. J Biol Chem. 1997 Jun 6;272(23):15011–15016. [PubMed]
  • 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. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3712–3717. [PMC free article] [PubMed]
  • Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG. The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits. J Biol Chem. 2000 Jul 28;275(30):23120–23126. [PubMed]
  • Gaidarov I, Krupnick JG, Falck JR, Benovic JL, Keen JH. Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. EMBO J. 1999 Feb 15;18(4):871–881. [PMC free article] [PubMed]
  • McDonald PH, Cote NL, Lin FT, Premont RT, Pitcher JA, Lefkowitz RJ. Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. J Biol Chem. 1999 Apr 16;274(16):10677–10680. [PubMed]
  • 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. J Biol Chem. 2001 Nov 9;276(45):42509–42513. [PubMed]
  • Bhattacharya Moshmi, Anborgh Pieter H, Babwah Andy V, Dale Lianne B, Dobransky Tomas, Benovic Jeffery L, Feldman Ross D, Verdi Joseph M, Rylett R Jane, Ferguson Stephen S G. Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization. Nat Cell Biol. 2002 Aug;4(8):547–555. [PubMed]
  • Lin FT, Krueger KM, Kendall HE, Daaka Y, Fredericks ZL, Pitcher JA, Lefkowitz RJ. Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. J Biol Chem. 1997 Dec 5;272(49):31051–31057. [PubMed]
  • Lin Fang-Tsyr, Chen Wei, Shenoy Sudha, Cong Mei, Exum Sabrina T, Lefkowitz Robert J. Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors. Biochemistry. 2002 Aug 27;41(34):10692–10699. [PubMed]
  • Kim You-Me, Barak Larry S, Caron Marc G, Benovic Jeffrey L. Regulation of arrestin-3 phosphorylation by casein kinase II. J Biol Chem. 2002 May 10;277(19):16837–16846. [PubMed]
  • Oakley RH, Laporte SA, Holt JA, Caron MG, Barak LS. Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J Biol Chem. 2000 Jun 2;275(22):17201–17210. [PubMed]
  • 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*. J Biol Chem. 2001 Jun 1;276(22):19452–19460. [PubMed]
  • Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425–479. [PubMed]
  • Hochstrasser M. Ubiquitin-dependent protein degradation. Annu Rev Genet. 1996;30:405–439. [PubMed]
  • Rubin DM, Finley D. Proteolysis. The proteasome: a protein-degrading organelle? Curr Biol. 1995 Aug 1;5(8):854–858. [PubMed]
  • Hartmann-Petersen Rasmus, Seeger Michael, Gordon Colin. Transferring substrates to the 26S proteasome. Trends Biochem Sci. 2003 Jan;28(1):26–31. [PubMed]
  • Ciechanover A, Gonen H, Bercovich B, Cohen S, Fajerman I, Israël A, Mercurio F, Kahana C, Schwartz AL, Iwai K, et al. Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105. Biochimie. 2001 Mar-Apr;83(3-4):341–349. [PubMed]
  • Orian A, Schwartz AL, Israël A, Whiteside S, Kahana C, Ciechanover A. Structural motifs involved in ubiquitin-mediated processing of the NF-kappaB precursor p105: roles of the glycine-rich region and a downstream ubiquitination domain. Mol Cell Biol. 1999 May;19(5):3664–3673. [PMC free article] [PubMed]
  • Katzmann David J, Odorizzi Greg, Emr Scott D. Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol. 2002 Dec;3(12):893–905. [PubMed]
  • Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science. 2001 Nov 9;294(5545):1307–1313. [PubMed]
  • Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997 Dec 22;420(1):25–27. [PubMed]
  • Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 2000 Mar 24;275(12):8945–8951. [PubMed]
  • Marchese A, Benovic JL. Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J Biol Chem. 2001 Dec 7;276(49):45509–45512. [PubMed]
  • Hicke L, Zanolari B, Riezman H. Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization. J Cell Biol. 1998 Apr 20;141(2):349–358. [PMC free article] [PubMed]
  • Terrell J, Shih S, Dunn R, Hicke L. A function for monoubiquitination in the internalization of a G protein-coupled receptor. Mol Cell. 1998 Jan;1(2):193–202. [PubMed]
  • Dunn R, Hicke L. Multiple roles for Rsp5p-dependent ubiquitination at the internalization step of endocytosis. J Biol Chem. 2001 Jul 13;276(28):25974–25981. [PubMed]
  • Dunn R, Hicke L. Domains of the Rsp5 ubiquitin-protein ligase required for receptor-mediated and fluid-phase endocytosis. Mol Biol Cell. 2001 Feb;12(2):421–435. [PMC free article] [PubMed]
  • Roth AF, Davis NG. Ubiquitination of the PEST-like endocytosis signal of the yeast a-factor receptor. J Biol Chem. 2000 Mar 17;275(11):8143–8153. [PubMed]
  • Dalle Stéphane, Imamura Takeshi, Rose David W, Worrall Dorothy Sears, Ugi Satoshi, Hupfeld Christopher J, Olefsky Jerrold M. 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 Sep;22(17):6272–6285. [PMC free article] [PubMed]
  • Hupfeld Christopher J, Dalle Stephane, Olefsky Jerrold M. Beta -Arrestin 1 down-regulation after insulin treatment is associated with supersensitization of beta 2 adrenergic receptor Galpha s signaling in 3T3-L1 adipocytes. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):161–166. [PMC free article] [PubMed]
  • Lin FT, Daaka Y, Lefkowitz RJ. beta-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor. J Biol Chem. 1998 Nov 27;273(48):31640–31643. [PubMed]
  • Chen W, Hu LA, Semenov MV, Yanagawa S, Kikuchi A, Lefkowitz RJ, Miller WE. beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14889–14894. [PMC free article] [PubMed]
  • Chen Wei, ten Berge Derk, Brown Jeff, Ahn Seungkirl, Hu Liaoyuan A, Miller William E, Caron Marc G, Barak Larry S, Nusse Roel, Lefkowitz Robert J. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science. 2003 Sep 5;301(5638):1391–1394. [PubMed]
  • Luttrell LM, Daaka Y, Lefkowitz RJ. Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Curr Opin Cell Biol. 1999 Apr;11(2):177–183. [PubMed]
  • Miller WE, Maudsley S, Ahn S, Khan KD, Luttrell LM, Lefkowitz RJ. beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis. J Biol Chem. 2000 Apr 14;275(15):11312–11319. [PubMed]
  • Ahn S, Maudsley S, Luttrell LM, Lefkowitz RJ, Daaka Y. Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling. J Biol Chem. 1999 Jan 15;274(3):1185–1188. [PubMed]
  • DeFea KA, Vaughn ZD, O'Bryan EM, Nishijima D, Déry O, Bunnett NW. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta -arrestin-dependent scaffolding complex. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11086–11091. [PMC free article] [PubMed]
  • Imamura T, Huang J, Dalle S, Ugi S, Usui I, Luttrell LM, Miller WE, Lefkowitz RJ, Olefsky JM. beta -Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport. J Biol Chem. 2001 Nov 23;276(47):43663–43667. [PubMed]
  • Barlic J, Andrews JD, Kelvin AA, Bosinger SE, DeVries ME, Xu L, Dobransky T, Feldman RD, Ferguson SS, Kelvin DJ. Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI. Nat Immunol. 2000 Sep;1(3):227–233. [PubMed]
  • Elion EA. The Ste5p scaffold. J Cell Sci. 2001 Nov;114(Pt 22):3967–3978. [PubMed]
  • Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI. JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway. Mol Cell Biol. 1999 Nov;19(11):7539–7548. [PMC free article] [PubMed]
  • Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ. The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999 Oct;19(10):7245–7254. [PMC free article] [PubMed]
  • 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. 2000 Nov 24;290(5496):1574–1577. [PubMed]
  • DeFea KA, Zalevsky J, Thoma MS, Déry O, Mullins RD, Bunnett NW. beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol. 2000 Mar 20;148(6):1267–1281. [PMC free article] [PubMed]
  • 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. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2449–2454. [PMC free article] [PubMed]
  • Tohgo Akira, Pierce Kristen L, Choy Eric W, Lefkowitz Robert J, Luttrell Louis M. beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J Biol Chem. 2002 Mar 15;277(11):9429–9436. [PubMed]
  • Tohgo Akira, Choy Eric W, Gesty-Palmer Diane, Pierce Kristen L, Laporte Stephane, Oakley Robert H, Caron Marc G, Lefkowitz Robert J, Luttrell Louis M. The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation. J Biol Chem. 2003 Feb 21;278(8):6258–6267. [PubMed]
  • Lin FT, Miller WE, Luttrell LM, Lefkowitz RJ. Feedback regulation of beta-arrestin1 function by extracellular signal-regulated kinases. J Biol Chem. 1999 Jun 4;274(23):15971–15974. [PubMed]
  • Pitcher JA, Tesmer JJ, Freeman JL, Capel WD, Stone WC, Lefkowitz RJ. Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases. J Biol Chem. 1999 Dec 3;274(49):34531–34534. [PubMed]
  • Ogier-Denis E, Pattingre S, El Benna J, Codogno P. Erk1/2-dependent phosphorylation of Galpha-interacting protein stimulates its GTPase accelerating activity and autophagy in human colon cancer cells. J Biol Chem. 2000 Dec 15;275(50):39090–39095. [PubMed]
  • Maller JL, Schwab MS, Roberts BT, Gross SD, Taieb FE, Tunquist BJ. The pathway of MAP kinase mediation of CSF arrest in Xenopus oocytes. Biol Cell. 2001 Sep;93(1-2):27–33. [PubMed]
  • Sun Yue, Cheng Zhijie, Ma Lan, Pei Gang. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem. 2002 Dec 20;277(51):49212–49219. [PubMed]
  • Miller William E, Houtz Daniel A, Nelson Christopher D, Kolattukudy PE, Lefkowitz Robert J. G-protein-coupled receptor (GPCR) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCR. J Biol Chem. 2003 Jun 13;278(24):21663–21671. [PubMed]
  • Parent CA, Devreotes PN. A cell's sense of direction. Science. 1999 Apr 30;284(5415):765–770. [PubMed]
  • Fong Alan M, Premont Richard T, Richardson Ricardo M, Yu Yen-Rei A, Lefkowitz Robert J, Patel Dhavalkumar D. Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7478–7483. [PMC free article] [PubMed]
  • Ge Lan, Ly Youly, Hollenberg Morley, DeFea Kathryn. A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem. 2003 Sep 5;278(36):34418–34426. [PubMed]
  • Alloway PG, Howard L, Dolph PJ. The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration. Neuron. 2000 Oct;28(1):129–138. [PubMed]
  • Kiselev A, Socolich M, Vinós J, Hardy RW, Zuker CS, Ranganathan R. A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila. Neuron. 2000 Oct;28(1):139–152. [PubMed]
  • Ranganathan Rama. Cell biology. A matter of life or death. Science. 2003 Mar 14;299(5613):1677–1679. [PubMed]
  • Acharya Usha, Patel Shetal, Koundakjian Edmund, Nagashima Kunio, Han Xianlin, Acharya Jairaj K. Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration. Science. 2003 Mar 14;299(5613):1740–1743. [PubMed]
  • Wang Ping, Gao Hua, Ni Yanxiang, Wang Beibei, Wu Yalan, Ji Lili, Qin Linhua, Ma Lan, Pei Gang. Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2. J Biol Chem. 2003 Feb 21;278(8):6363–6370. [PubMed]
  • Scott Mark G H, Le Rouzic Erwann, Périanin Axel, Pierotti Vincenzo, Enslen Hervé, Benichou Serge, Marullo Stefano, Benmerah Alexandre. Differential nucleocytoplasmic shuttling of beta-arrestins. Characterization of a leucine-rich nuclear export signal in beta-arrestin2. J Biol Chem. 2002 Oct 4;277(40):37693–37701. [PubMed]
  • Wang Ping, Wu Yalan, Ge Xin, Ma Lan, Pei Gang. Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus. J Biol Chem. 2003 Mar 28;278(13):11648–11653. [PubMed]
  • Mahanty SK, Wang Y, Farley FW, Elion EA. Nuclear shuttling of yeast scaffold Ste5 is required for its recruitment to the plasma membrane and activation of the mating MAPK cascade. Cell. 1999 Aug 20;98(4):501–512. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...