Abstract
The four members of the mammalian arrestin family, two visual and two nonvisual, share the property of stimulus-dependent docking to G protein-coupled receptors. This conformational selectivity permits them to function in receptor desensitization, as arrestin binding sterically inhibits G protein coupling. The two nonvisual arrestins further act as adapter proteins, linking receptors to the clathrin-dependent endocytic machinery and regulating receptor sequestration, intracellular trafficking, recycling, and degradation. Arrestins also function as ligand-regulated scaffolds, recruiting catalytically active proteins into receptor-based multiprotein “signalsome” complexes. Arrestin binding thus marks the transition from a transient G protein-coupled state on the plasma membrane to a persistent arrestin-coupled state that continues to signal as the receptor internalizes. Two of the earliest discovered and most studied arrestin-dependent signaling pathways involve regulation of Src family nonreceptor tyrosine kinases and the ERK1/2 mitogen-activated kinase cascade. In each case, arrestin scaffolding imposes constraints on kinase activity that dictate signal duration and substrate specificity. Evidence suggests that arrestin-bound ERK1/2 and Src not only play regulatory roles in receptor desensitization and trafficking but also mediate longer term effects on cell growth, migration, proliferation, and survival.
Keywords
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- BRET:
-
Bioluminescence resonance energy transfer
- EGF:
-
Epidermal growth factor
- ERK1/2:
-
Extracellular signal-regulated kinases 1 and 2
- GPCR:
-
G protein-coupled receptor
- GRK:
-
GPCR kinase
- JNK/SAPK:
-
c-Jun N-terminal kinase/stress-activated protein kinase
- LPA:
-
Lysophosphatidic acid
- MAPK:
-
Mitogen-activated protein kinase
- MEF:
-
Murine embryo fibroblast
- PAR:
-
Protease-activated receptor
- PK:
-
Protein kinase
- PLC:
-
Phospholipase C
- PTH:
-
Parathyroid hormone
- SH:
-
Src homology
References
Ahn S, Maudsley S, Luttrell LM et al (1999) Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling. J Biol Chem 274:1185–1188
Ahn S, Kim J, Lucaveche CL et al (2002) Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor. J Biol Chem 277:26642–26651
Ahn S, Shenoy SK, Wei H et al (2004a) Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor. J Biol Chem 279:35518–35525
Ahn S, Wei H, Garrison TR et al (2004b) Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2. J Biol Chem 279:7807–7811
Aplin M, Christensen GL, Schneider M et al (2007) Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes. Basic Clin Pharmacol Toxicol 100:296–301
Appleton KM, Lee MH, Alele C (2013) Biasing the parathyroid hormone receptor: relating in vitro ligand efficacy to in vivo biological activity. Methods Enzymol 522:229–262
Aragay AM, Mellado M, Frade JM et al (1998) Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2. Proc Natl Acad Sci USA 95:2985–2990
Azzi M, Charest PG, Angers S et al (2003) Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc Natl Acad Sci USA 100:11406–11411
Barlic J, Andrews JD, Kelvin AA et al (2000) Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI. Nat Immunol 1:227–233
Barnes WG, Reiter E, Violin JD et al (2005) beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. J Biol Chem 280:8041–8050
Bhandari D, Trejo J, Benovic JL et al (2007) Arrestin-2 interacts with the ubiquitin-protein isopeptide ligase atrophin-interacting protein 4 and mediates endosomal sorting of the chemokine receptor CXCR4. J Biol Chem 282:36971–36979
Brahmbhatt AA, Klemke RL (2003) ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis. J Biol Chem 278:13016–13025
Breitman M, Kook S, Gimenez LE et al (2012) Silent scaffolds: inhibition of c-Jun N-terminal kinase 3 activity in cell by dominant-negative arrestin-3 mutant. J Biol Chem 287:19653–19664
Brinson RE, Harding T, Diliberto PA et al (1998) Regulation of a calcium-dependent tyrosine kinase in vascular smooth muscle cells by angiotensin II and platelet-derived growth factor. Dependence on calcium and the actin cytoskeleton. J Biol Chem 273:1711–1718
Burack WR, Shaw AS (2000) Signal transduction: hanging on a scaffold. Curr Opin Cell Biol 12:211–216
Carpenter G (2000) EGF receptor transactivation mediated by the proteolytic production of EGF-like agonists. Sci STKE 2000(15):pe1
Cheung R, Malik M, Ravyn V et al (2009) An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages. J Leukoc Biol 86:833–845
Choi KY, Satterberg B, Lyons DM et al (1994) Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae. Cell 78:499–512
Christopoulos A, Kenakin T (2002) G protein-coupled receptor allosterism and complexing. Pharmacol Rev 54:323–374
Chun KS, Lao HC, Trempus CS et al (2009) The prostaglandin receptor EP2 activates multiple signaling pathways and beta-arrestin1 complex formation during mouse skin papilloma development. Carcinogenesis 30:1620–1627
Coffa S, Breitman M, Hanson SM et al (2011a) The effect of arrestin conformation on the recruitment of c-Raf1, MEK1, and ERK1/2 activation. PloS One 6:e28723
Coffa S, Breitman M, Spiller BW et al (2011b) A single mutation in arrestin-2 prevents ERK1/2 activation by reducing c-Raf1 binding. Biochemistry 50:6951–6958
Daaka Y, Luttrell LM, Ahn S (1998) Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J Biol Chem 273:685–688
Dasgupta P, Rastogi S, Pillai S et al (2006) Nicotine induces cell proliferation by beta-arrestin-mediated activation of Src and Rb-Raf-1 pathways. J Clin Invest 116:2208–2217
DeFea KA, Zalevsky J, Thoma MS et al (2000a) beta-Arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol 148:1267–1281
DeFea KA, Vaughn ZD, O’Bryan EM et al (2000b) The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta-arrestin-dependent scaffolding complex. Proc Natl Acad Sci USA 97:11086–11091
Della Rocca GJ, Maudsley SR, Daaka Y et al (1999) Pleiotropic coupling of G protein-coupled receptors to the mitogen-activated protein kinase cascade. Role of focal adhesions and receptor tyrosine kinases. J Biol Chem 274:13978–13984
DeRooij J, Zwartkruis FL, Verheijen MH et al (1998) Epac is a Rap1 guanine nucleotide exchange factor directly activated by cAMP. Nature 396:474–477
DeWire SM, Kim J, Whalen EJ et al (2008) Beta-arrestin-mediated signaling regulates protein synthesis. J Biol Chem 283:10611–10620
Dikic I, Tokiwa G, Lev S et al (1996) A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation. Nature 383:547–550
Dikic I, Dikic I, Schlessinger J (1998) Identification of a new Pyk2 isoform implicated in chemokine and antigen receptor signaling. J Biol Chem 273:14301–14308
Drake MT, Violin JD, Whalen EJ et al (2008) beta-Arrestin-biased agonism at the beta2-adrenergic receptor. J Biol Chem 283:5669–5676
Elorza A, Samago S, Mayor F Jr (2000) Agonist-dependent modulation of G protein-coupled receptor kinase 2 by mitogen-activated protein kinases. Mol Pharmacol 57:778–783
Elorza A, Penela P, Sarnago S et al (2003) MAPK-dependent degradation of G protein-coupled receptor kinase 2. J Biol Chem 278:29164–29173
Erpel T, Courtneidge SA (1995) Src family protein tyrosine kinases and cellular signal transduction pathways. Curr Opin Cell Biol 7:176–182
Fan G, Shumay E, Malbon CC et al (2001) c-Src tyrosine kinase binds the beta2-adrenergic receptor via phospho-Tyr-350, phosphorylates G-protein-linked receptor kinase 2, and mediates agonist-induced receptor desensitization. J Biol Chem 276:13240–13247
Ferguson SS (2001) Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev 53:1–24
Fessart D, Simaan M, Laporte SA (2005) c-Src regulates clathrin adapter protein 2 interaction with beta-arrestin and the angiotensin II type 1 receptor during clathrin-mediated internalization. Mol Endocrinol 19:491–503
Fessart D, Simaan M, Zimmerman B et al (2007) Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2 complex. J Cell Sci 120:1723–1732
Fong AM, Premont RT, Richardson RM et al (2002) Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci USA 99:7478–7483
Freedman NJ, Lefkowitz RJ (1996) Desensitization of G protein-coupled receptors. Recent Prog Horm Res 51:319–351
Galandrin S, Bouvier M (2006) Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol 70:1575–1584
Galet C, Ascoli M (2008) Arrestin-3 is essential for the activation of Fyn by the luteinizing hormone receptor (LHR) in MA-10 cells. Cell Signal 20:1822–2829
Ge L, Ly Y, Hollenberg M et al (2003) A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem 278:34418–34426
Ge L, Shenoy SK, Lefkowitz RJ et al (2004) Constitutive protease-activated receptor-2-mediated migration of MDA MB-231 breast cancer cells requires both beta-arrestin-1 and -2. J Biol Chem 279:55419–55424
Gesty-Palmer D, El Shewy H, Kohout TA et al (2005) beta-Arrestin 2 expression determines the transcriptional response to lysophosphatidic acid stimulation in murine embryo fibroblasts. J Biol Chem 280:32157–32167
Gesty-Palmer D, Chen M, Reiter E et al (2006) Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J Biol Chem 281:10856–10864
Gesty-Palmer D, Flannery P, Yuan L et al (2009) A beta-arrestin biased agonist of the parathyroid hormone receptor (PTH1R) promotes bone formation independent of G protein activation. Sci Transl Med 1:1ra1
Gesty-Palmer D, Liao S, Yuan L et al (2013) beta-Arrestin pathway-selective G protein-coupled receptor agonists engender unique biological efficacy in vivo. Mol Endocrinol 27:296–314
Ghalayini AJ, Desai N, Smith KR et al (2002) Light-dependent association of Src with photoreceptor rod outer segment membrane proteins in vivo. J Biol Chem 277:1469–1476
Hanson SM, Cleghorn WM, Francis DJ et al (2007) Arrestin mobilizes signaling proteins to the cytoskeleton and redirects their activity. J Mol Biol 368:375–387
Haskell MD, Slack JK, Parsons JT et al (2001) c-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes. Chem Rev 101:2425–2440
Hawes BE, van Biesen T, Koch WJ et al (1995) Distinct pathways of Gi- and Gq-mediated mitogen activated protein kinase activation. J Biol Chem 270:17148–17153
Heitzler D, Durand G, Gallay N et al (2012) Competing G protein-coupled receptor kinases balance G protein and beta-arrestin signaling. Mol Syst Biol 8:590
Holloway AC, Qian H, Pipolo L et al (2002) Side-chain substitutions within angiotensin II reveal different requirements for signaling, internalization, and phosphorylation of type 1A angiotensin receptors. Mol Pharmacol 61:768–777
Hunton DL, Barnes WG, Kim J et al (2005) Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxis. Mol Pharmacol 67:1229–1236
Hupfeld CJ, Resnik JL, Ugi S et al (2005) Insulin-induced beta-arrestin1 Ser-412 phosphorylation is a mechanism for desensitization of ERK activation by Galphai-coupled receptors. J Biol Chem 280:1016–1023
Ignatova EG, Belcheva MM, Bohn LM et al (1999) Requirement of receptor internalization for opioid stimulation of mitogen-activated protein kinase: biochemical and immunofluorescence confocal microscopic evidence. J Neurosci 19:56–63
Imamura T, Huang J, Dalle S et al (2001) beta-Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport. J Biol Chem 276:43663–43667
Jafri F, El-Shewy HM, Lee MH et al (2006) Constitutive ERK1/2 activation by a chimeric neurokinin 1 receptor-beta-arrestin1 fusion protein. Probing the composition and function of the G protein-coupled receptor “signalsome”. J Biol Chem 281:19346–19357
Kenakin TP (1996) Receptor conformational induction versus selection: All part of the same energy landscape. Trends Pharmacol Sci 17:190–191
Kenakin T, Miller LE (2010) Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 62:265–304
Kendall RT, Strungs EG, Rachidi SM et al (2011) The beta-arrestin pathway-selective type 1A angiotensin receptor (AT1A) agonist [Sar1, Ile4, Ile8]angiotensin II regulates a robust G protein-independent signaling network. J Biol Chem 286:19880–19891
Kim J, Ahn S, Ren XR (2005) Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling. Proc Natl Acad Sci USA 102:1442–1447
Kim J, Zhang L, Peppel K et al (2008) Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration. Circ Res 103:70–79
Kim J, Ahn S, Rajagopal K et al (2009) 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 284:11953–11962
Kohout TA, Nicholas SL, Perry SJ et al (2004) Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J Biol Chem 279:23214–23222
Kolch W, Heldecker G, Kochs G et al (1993) Protein kinase C alpha activates Raf-1 by direct phosphorylation. Nature 364:249–255
Kryiakis JM, Avruch J (1996) Sounding the alarm: protein kinase cascades activated by stress and inflammation. J Biol Chem 271:24313–24316
Kuo F-T, Lu T-L, Fu H-W (2006) Opposing effects of beta-arrestin1 and beta-arrestin2 on activation and degradation of Src induced by protease-activated receptor 1. Cell Signal 18:1914–1923
Lee M-H, El-Shewy HM, Luttrell DK et al (2008) Role of beta-arrestin-mediated desensitization and signaling in the control of angiotensin AT1a receptor-stimulated transcription. J Biol Chem 283:2088–2097
Lee SH, Hollingsworth R, Kwon HY et al (2012) beta-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser(83) and microglia chemotaxis. Glia 60:1366–1377
Lefkowitz RJ, Pierce KL, Luttrell LM (2002) Dancing with different partners: PKA phosphorylation of seven membrane-spanning receptors regulates their G protein coupling specificity. Mol Pharm 62:971–974
Lev S, Moreno H, Martinez R et al (1995) Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature 376:737–745
Li X, Hunter D, Morris J et al (1998) A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation by a two-stage process involving adherence and a subsequent intracellular signal. J Biol Chem 273:9361–9364
Lin FT, Krueger KM, Kendall HE et al (1997) Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. J Biol Chem 272:31051–31057
Lin FT, Miller WE, Luttrell LM et al (1999) Feedback regulation of beta-arrestin1 function by extracellular signal-regulated kinases. J Biol Chem 274:15971–15974
Lin FT, Chen W, Shenoy S et al (2002) Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors. Biochemistry 41:10692–10699
Liu X, Pawson T (1994) Biochemistry of the Src protein-tyrosine kinase: regulation by SH2 and SH3 domains. Recent Prog Horm Res 49:149–160
Luttrell LM (2003) Location, Location, Location. Spatial and temporal regulation of MAP kinases by G protein-coupled receptors. J Mol Endo 30:117–126
Luttrell LM, Gesty-Palmer D (2010) Beyond desensitization: physiological relevance of arrestin-dependent signaling. Pharmacol Rev 62:305–330
Luttrell LM, Kenakin TP (2011) Refining efficacy: allosterism and bias in G protein-coupled receptor signaling. Methods Mol Biol 756:3–35
Luttrell LM, Lefkowitz RJ (2002) The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115:455–465
Luttrell DK, Luttrell LM (2004) Not so strange bedfellows: G-protein-coupled receptors and Src family kinases. Oncogene 23:7969–7978
Luttrell LM, Hawes BE, van Biesen T et al (1996) Role of c-Src in G protein-coupled receptor- and Gbetagamma subunit-mediated activation of mitogen activated protein kinases. J Biol Chem 271:19443–19450
Luttrell LM, Della Rocca GJ, van Biesen T et al (1997) Gbetagamma subunits mediate Src-dependent phosphorylation of the epidermal growth factor receptor. J Biol Chem 272:4637–4644
Luttrell LM, Ferguson SS, Daaka Y et al (1999) Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283:655–661
Luttrell LM, Roudabush FL, Choy EW et al (2001) Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci USA 98:2449–2454
Machesky LM (1997) Cell motility: complex dynamics at the leading edge. Curr Biol 7:R164–R167
Maudsley S, Martin B, Luttrell LM (2005) Perspectives in pharmacology: the origins of diversity and specificity in G protein-coupled receptor signaling. J Pharmacol Exp Ther 314:485–494
McDonald PH, Chow CW, Miller WE et al (2000) Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290:1574–1577
Meng D, Lynch MJ, Huston E et al (2009) MEK1 binds directly to beta-arrestin1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization. J Biol Chem 284:11425–11435
Miller WE, Maudsley S, Ahn S et al (2000) 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 275:11312–11319
Miller WE, McDonald PH, Cai SF et al (2001) Identification of a motif in the carboxyl terminus of beta-arrestin2 responsible for activation of JNK3. J Biol Chem 276:27770–27777
Miura S, Zhang J, Matsuo Y et al (2004) Activation of extracellular signal-activated kinase by angiotensin II-induced Gq-independent epidermal growth factor receptor transactivation. Hypertens Res 27:765–770
Mossa O, Ashton AW, Fraig M et al (2008) Novel role of thromboxane receptors beta isoform in bladder cancer pathogenesis. Cancer Res 68:4097–4104
Nobles KN, Guan Z, Xiao K et al (2007) 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 282:21370–21381
Nobles KN, Xiao K, Ahn S et al (2011) Distinct phosphorylation sites on the β(2)-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin. Sci Signal 4:ra51
Noma T, Lemaire A, Naga Prasad SV et al (2007) Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection. J Clin Invest 117:2445–2458
Oakley RH, Laporte SA, Holt JA et al (2000) Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J Biol Chem 275:17201–17210
Ozawa K, Whalen EJ, Nelson CD et al (2008) S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking. Mol Cell 31:395–405
Parent JL, Labrecque P, Orsini MJ et al (1999) Internalization of the TXA2 receptor alpha and beta isoforms. Role of the differentially spliced COOH terminus in agonist-promoted receptor internalization. J Biol Chem 274:8941–8948
Pearson G, Robinson F, Beers Gibson T et al (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiologic functions. Endocr Rev 22:153–183
Penela P, Elorza A, Sarnago S et al (2001) Beta-arrestin- and c-Src-dependent degradation of G-protein-coupled receptor kinase 2. EMBO J 20:5129–5138
Pierce KL, Luttrell LM, Lefkowitz RJ (2001a) New mechanisms in heptahelical receptor signaling to mitogen activated protein kinase cascades. Oncogene 20:1532–1539
Pierce KL, Tohgo A, Ahn S et al (2001b) Epidermal growth factor (EGF) receptor-dependent ERK activation by G protein-coupled receptors: a co-culture system for identifying intermediates upstream and downstream of heparin-binding EGF shedding. J Biol Chem 276:23155–23160
Pitcher JA, Tesmer JG, Freeman JL et al (1999) Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases. J Biol Chem 274:34531–34534
Prenzel N, Zwick E, Daub H et al (1999) EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402:884–888
Ren XR, Reiter E, Ahn S et al (2005) Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor. Proc Natl Acad Sci USA 102:1448–1453
Ross EM, Wilkie TM (2000) GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 69:795–827
Samama P, Cotecchia S, Costa T et al (1993) A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model. J Biol Chem 268:4625–4636
Sarnago S, Elorza A, Mayor F Jr (1999) Agonist-dependent phosphorylation of the G protein-coupled receptor kinase 2 (GRK2) by Src tyrosine kinase. J Biol Chem 274:34411–34416
Scott MG, Le Rouzic E, Perianin A et al (2002) Differential nucleocytoplasmic shuttling of beta-arrestins. Characterization of a leucine-rich nuclear export signal in beta-arrestin2. J Biol Chem 277:37693–37701
Scott MG, Pierotti V, Storez H et al (2006) Cooperative regulation of extracellular signal-regulated kinase activation and cell shape change by filamin A and beta-arrestins. Mol Cell Biol 26:3432–3445
Seo J, Tsakem EL, Breitman M et al (2011) Identification of arrestin-3-specific residues necessary for JNK3 kinase activation. J Biol Chem 286:27894–27901
Seta K, Nanamori M, Modrall JG et al (2002) AT1 receptor mutant lacking heterotrimeric G protein coupling activates the Src-Ras-ERK pathway without nuclear translocation of ERKs. J Biol Chem 277:9268–9277
Shenoy SK (2007) Seven-transmembrane receptors and ubiquitination. Circ Res 100:1142–1154
Shenoy SK, Lefkowitz RJ (2003) Trafficking pattern of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J Biol Chem 278:14498–14506
Shenoy SK, Lefkowitz RJ (2005) Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes. J Biol Chem 280:15315–15324
Shenoy SK, McDonald PH, Kohout TA et al (2001) Regulation of receptor fate by ubiquitination of activated beta2-adrenergic receptor and beta-arrestin. Science 294:1307–1313
Shenoy SK, Drake MT, Nelson CD et al (2006) beta-Arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor. J Biol Chem 281:1261–1273
Shenoy SK, Barak LS, Xiao K et al (2007) Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation. J Biol Chem 282:29549–29562
Shenoy SK, Xiao K, Venkataramanan V et al (2008) Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor. J Biol Chem 283:22166–22176
Shenoy SK, Modi AS, Shukla AK et al (2009) Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2. Proc Natl Acad Sci USA 106:6650–6655
Shukla AK, Violin JD, Whalen EJ et al (2008) Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptors. Proc Natl Acad Sci USA 105:9988–9993
Song X, Raman D, Gurevich EV et al (2006) Visual and both non-visual arrestins in their “inactive” conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm. J Biol Chem 281:21491–21499
Song X, Coffa S, Fu H et al (2009) How does arrestin assemble MAPKs into a signaling complex? J Biol Chem 284:685–695
Stoffel RH III, Pitcher JA, Lefkowitz RJ (1997) Targeting G protein-coupled receptor kinases to their receptor substrates. J Membr Biol 157:1–8
Stokoe D, Macdonald SG, Cadwallader K et al (1994) Activation of Raf as a result of recruitment to the plasma membrane. Science 264:1463–1467
Stork PJ (2002) ERK signaling: duration, duration, duration. Cell Cycle 1:315–317
Sullivan SK, McGrath DA, Grigoriadis D et al (1999) Pharmacological and signaling analysis of human chemokine receptor CCR-7 stably expressed in HEK-293 cells: high-affinity binding of recombinant ligands MIP-3beta and SLC stimulates multiple signaling cascades. Biochem Biophys Res Commun 263:685–690
Superti-Furga G, Courtneidge SA (1995) Structure-function relationships in Src family and related protein tyrosine kinases. Bioessays 17:321–330
Talbot J, Joly E, Prentki M et al (2012) beta-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. Mol Cell Endocrinol 364:65–70
Terrillon S, Bouvier M (2004) Receptor activity-independent recruitment of beta-arrestin2 reveals specific signalling modes. EMBO J 23:3950–3961
Tohgo A, Pierce KL, Choy EW et al (2002) beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK mediated transcription following angiotensin AT1a receptor stimulation. J Biol Chem 277:9429–9436
Tohgo A, Choy EW, Gesty-Palmer D et al (2003) The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation. J Biol Chem 278:6258–6267
van Biesen T, Hawes BE, Luttrell DK et al (1995) Receptor tyrosine kinase- and Gbetagamma-mediated MAP kinase activation by a common signalling pathway. Nature 376:781–784
Vossler MR, Yao H, York RD et al (1997) cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap-1-dependent pathway. Cell 89:73–82
Wang Y, Tang Y, Teng L et al (2006) Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 7:139–147
Wei H, Ahn S, Shenoy SK et al (2003) Independent G protein and beta-arrestin2 mediated activation of ERK by angiotensin. Proc Natl Acad Sci USA 100:10782–10787
Werbonat Y, Kleutges N, Jakobs KH et al (2000) Essential role of dynamin in internalization of M2 muscarinic acetylcholine and angiotensin AT1A receptors. J Biol Chem 275:21969–21974
Whalen EJ, Rajagopal S, Lefkowitz RJ (2011) Therapeutic potential of β-arrestin- and G protein-biased agonists. Trends Mol Med 17:126–139
Whitmarsh AJ, Cavanagh J, Tournier C et al (1998) A mammalian scaffold complex that selectively mediates MAP kinase activation. Science 281:1671–1674
Wisler JW, DeWire SM, Whalen EJ et al (2007) A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci USA 104:16657–16662
Wu J, Dent P, Jelinek T et al (1993) Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3’,5’-monophosphate. Science 62:1065–1068
Xiao K, Shenoy SK, Nobles K et al (2004) Activation-dependent conformational changes in beta-arrestin 2. J Biol Chem 279:55744–55753
Xiao K, Sun J, Kim J et al (2010) Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci USA 107:15299–15304
Zidar DA, Violin JD, Whalen EJ et al (2009) Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands. Proc Natl Acad Sci USA 106:9649–9654
Zimmerman B, Simaan M, Lee M-H et al (2009) c-Src-mediated phosphorylation of AP-2 reveals a general mechanism for receptors internalizing through the clathrin pathway. Cell Signal 21:103–110
Zoudilova M, Kumar P, Ge L et al (2007) Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem 282:20634–20646
Acknowledgments
Work conducted in the authors’ laboratory is supported by National Institutes of Health Grant R01 DK055524 and the Research Service of the Charleston, SC Veterans Affairs Medical Center. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government.
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Strungs, E.G., Luttrell, L.M. (2014). Arrestin-Dependent Activation of ERK and Src Family Kinases. In: Gurevich, V. (eds) Arrestins - Pharmacology and Therapeutic Potential. Handbook of Experimental Pharmacology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41199-1_12
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