arrestins

Summary

Summary: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.

Top Publications

  1. Yang C, Huang H, Chen K, Chen Y, Sheen Chen S, Lin C. Antinociceptive potentiation and attenuation of tolerance by intrathecal ?-arrestin 2 small interfering RNA in rats. Br J Anaesth. 2011;107:774-81 pubmed publisher
    ..This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain. ..
  2. Penn R, Bond R, Walker J. GPCRs and arrestins in airways: implications for asthma. Handb Exp Pharmacol. 2014;219:387-403 pubmed publisher
    ..The capacity of arrestins to regulate GPCR signaling, via either control of GPCR desensitization/resensitization or G protein-independent ..
  3. Barak L, Peterson S. Modeling of bias for the analysis of receptor signaling in biochemical systems. Biochemistry. 2012;51:1114-25 pubmed publisher
  4. Lymperopoulos A, Bathgate A. Pharmacogenomics of the heptahelical receptor regulators G-protein-coupled receptor kinases and arrestins: the known and the unknown. Pharmacogenomics. 2012;13:323-41 pubmed publisher
    ..The present review will discuss what is known so far in this evolving field of GRK/Arr pharmacogenomics, as well as highlight important areas likely to produce invaluable information in the future. ..
  5. Bychkov E, Ahmed M, Gurevich V, Benovic J, Gurevich E. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis. 2011;44:248-58 pubmed publisher
    ..G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions...
  6. Tilley D. G protein-dependent and G protein-independent signaling pathways and their impact on cardiac function. Circ Res. 2011;109:217-30 pubmed publisher
  7. Deng H, Hu H, Fang Y. Tyrphostin analogs are GPR35 agonists. FEBS Lett. 2011;585:1957-62 pubmed publisher
    ..These agonists provide pharmacological tools to study the biology and function of GPR35. ..
  8. Lima Fernandes E, Enslen H, Camand E, Kotelevets L, Boularan C, Achour L, et al. Distinct functional outputs of PTEN signalling are controlled by dynamic association with ?-arrestins. EMBO J. 2011;30:2557-68 pubmed publisher
    ..We report that the scaffolding proteins ?-arrestins (?-arrs) are important regulators of PTEN...
  9. Nobles K, Xiao K, Ahn S, Shukla A, Lam C, Rajagopal S, et al. Distinct phosphorylation sites on the ?(2)-adrenergic receptor establish a barcode that encodes differential functions of ?-arrestin. Sci Signal. 2011;4:ra51 pubmed publisher
    ..plays essential roles in the regulation of receptor function by promoting interactions of the receptors with ?-arrestins. These multifunctional adaptor proteins desensitize GPCRs, by reducing receptor coupling to G proteins and ..

More Information

Publications62

  1. 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
    ..promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of ?-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right...
  2. Min J, DeFea K. ?-arrestin-dependent actin reorganization: bringing the right players together at the leading edge. Mol Pharmacol. 2011;80:760-8 pubmed publisher
    ..mediators of G-protein-coupled receptor desensitization and internalization and later as signaling platforms, ?-arrestins play a requisite role in chemotaxis and reorganization of the actin cytoskeleton, downstream of multiple ..
  3. Liu J, Horst R, KATRITCH V, Stevens R, Wuthrich K. Biased signaling pathways in ?2-adrenergic receptor characterized by 19F-NMR. Science. 2012;335:1106-10 pubmed publisher
    ..The selective effects of different ligands on the conformational equilibria involving helices VI and VII provide insights into the long-range structural plasticity of ?(2)AR in partial and biased agonist signaling...
  4. Dang V, Chieng B, Azriel Y, Christie M. Cellular morphine tolerance produced by ?arrestin-2-dependent impairment of ?-opioid receptor resensitization. J Neurosci. 2011;31:7122-30 pubmed publisher
  5. Ramachandran R, Mihara K, Chung H, Renaux B, Lau C, Muruve D, et al. Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2). J Biol Chem. 2011;286:24638-48 pubmed publisher
    ..Our data illustrate a new mode of PAR regulation that involves biased PAR(2) signaling by neutrophil elastase and a disarming/silencing effect of cathepsin-G and proteinase-3. ..
  6. Burch M, Osman N, Getachew R, Al aryahi S, Poronnik P, Zheng W, et al. G protein coupled receptor transactivation: extending the paradigm to include serine/threonine kinase receptors. Int J Biochem Cell Biol. 2012;44:722-7 pubmed publisher
    ..These insights expand the possibilities for outcomes of therapeutically targeting GPCRs where more substantive and prolonged actions such as the synthesis of extracellular matrix may be affected. ..
  7. Vibhuti A, Gupta K, Subramanian H, Guo Q, Ali H. Distinct and shared roles of ?-arrestin-1 and ?-arrestin-2 on the regulation of C3a receptor signaling in human mast cells. PLoS ONE. 2011;6:e19585 pubmed publisher
    ..response that reflects G protein activation and a delayed response that is G protein independent but requires ?-arrestins. The role of ?-arrestins on C3aR activation/regulation in human mast cells, however, remains unknown...
  8. Ibrahim I, Kurose H. ?-arrestin-mediated signaling improves the efficacy of therapeutics. J Pharmacol Sci. 2012;118:408-12 pubmed
    b>Arrestins (?-arrestin-1 and ?-arrestin-2) were first identified as proteins that have the ability to desensitize G protein-coupled receptors (GPCRs)...
  9. Taguchi K, Kobayashi T, Matsumoto T, Kamata K. Dysfunction of endothelium-dependent relaxation to insulin via PKC-mediated GRK2/Akt activation in aortas of ob/ob mice. Am J Physiol Heart Circ Physiol. 2011;301:H571-83 pubmed publisher
  10. Porrello E, Pfleger K, Seeber R, Qian H, Oro C, Abogadie F, et al. Heteromerization of angiotensin receptors changes trafficking and arrestin recruitment profiles. Cell Signal. 2011;23:1767-76 pubmed publisher
  11. Patwari P, Lee R. An expanded family of arrestins regulate metabolism. Trends Endocrinol Metab. 2012;23:216-22 pubmed publisher
    The classical visual and ?-arrestins belong to a larger family of proteins that likely share structural similarity. Humans have an additional six related proteins sometimes termed the ?-arrestins, whose functions are now emerging...
  12. Nichols H, Saffeddine M, Theriot B, Hegde A, Polley D, El Mays T, et al. ?-Arrestin-2 mediates the proinflammatory effects of proteinase-activated receptor-2 in the airway. Proc Natl Acad Sci U S A. 2012;109:16660-5 pubmed publisher
    ..We hypothesized that the proinflammatory responses to PAR(2) activation are mediated by ?-arrestins, whereas the protective effects are not...
  13. Luttrell L, Miller W. Arrestins as regulators of kinases and phosphatases. Prog Mol Biol Transl Sci. 2013;118:115-47 pubmed publisher
    The discovery that, in addition to mediating G protein-coupled receptor (GPCR) desensitization and endocytosis, arrestins bind to diverse catalytically active nonreceptor proteins and act as ligand-regulated signaling scaffolds led to a ..
  14. Magnan R, Escrieut C, Gigoux V, De K, Clerc P, Niu F, et al. Distinct CCK-2 receptor conformations associated with ?-arrestin-2 recruitment or phospholipase-C activation revealed by a biased antagonist. J Am Chem Soc. 2013;135:2560-73 pubmed publisher
  15. Walther C, Ferguson S. Arrestins: role in the desensitization, sequestration, and vesicular trafficking of G protein-coupled receptors. Prog Mol Biol Transl Sci. 2013;118:93-113 pubmed publisher
    Over the years, ?-arrestins have emerged as multifunctional molecular scaffolding proteins regulating almost every imaginable G protein-coupled receptor (GPCR) function...
  16. Jensen D, Godfrey C, Niklas C, Canals M, Kocan M, Poole D, et al. The bile acid receptor TGR5 does not interact with ?-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts. J Biol Chem. 2013;288:22942-60 pubmed publisher
    ..stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of ?-arrestins, as assessed by confocal microscopy...
  17. Raehal K, Bohn L. ?-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia. Handb Exp Pharmacol. 2014;219:427-43 pubmed publisher
    ..In this chapter, we review the role of the intracellular regulatory proteins, ?-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and ..
  18. Boerrigter G, Lark M, Whalen E, Soergel D, Violin J, Burnett J. Cardiorenal actions of TRV120027, a novel ß-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and heart failure canines: a novel therapeutic strategy for acute heart failure. Circ Heart Fail. 2011;4:770-8 pubmed publisher
    ..TRV120027 is a novel ß-arrestin-biased AT1R ligand, which engages ß-arrestins while blocking G-protein signaling...
  19. Thathiah A, Horré K, Snellinx A, Vandewyer E, Huang Y, Ciesielska M, et al. ?-arrestin 2 regulates A? generation and ?-secretase activity in Alzheimer's disease. Nat Med. 2013;19:43-9 pubmed publisher
    b>arrestins are associated with numerous aspects of G protein-coupled receptor (GPCR) signaling and regulation and accordingly influence diverse physiological and pathophysiological processes...
  20. Zhan X, Kaoud T, Dalby K, Gurevich V. Nonvisual arrestins function as simple scaffolds assembling the MKK4-JNK3?2 signaling complex. Biochemistry. 2011;50:10520-9 pubmed publisher
    b>Arrestins make up a small family of proteins with four mammalian members that play key roles in the regulation of multiple G protein-coupled receptor-dependent and -independent signaling pathways...
  21. Gimenez L, Vishnivetskiy S, Baameur F, Gurevich V. Manipulation of very few receptor discriminator residues greatly enhances receptor specificity of non-visual arrestins. J Biol Chem. 2012;287:29495-505 pubmed publisher
    Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of "receptor discriminator" residues in arrestin-3...
  22. Gurevich V, Hanson S, Song X, Vishnivetskiy S, Gurevich E. The functional cycle of visual arrestins in photoreceptor cells. Prog Retin Eye Res. 2011;30:405-30 pubmed publisher
  23. Lefkowitz R. Arrestins come of age: a personal historical perspective. Prog Mol Biol Transl Sci. 2013;118:3-18 pubmed publisher
    Visual arrestin and the two ?-arrestins (1 and 2) were originally discovered 25-30 years ago in the context of their ability to desensitize phosphorylated G protein-coupled receptors (rhodopsin and the ?2-adrenergic receptor, ..
  24. Weeks K, Dwyer D, Aamodt E. Clozapine and lithium require Caenorhabditis elegans ?-arrestin and serum- and glucocorticoid-inducible kinase to affect Daf-16 (FOXO) localization. J Neurosci Res. 2011;89:1658-65 pubmed publisher
    ..Lithium, a mood stabilizer often used to treat psychosis, also requires ?-arrestin and SGK to suppress the nuclear localization of DAF-16. ..
  25. Shea F, ROWELL J, Li Y, Chang T, Alvarez C. Mammalian ? arrestins link activated seven transmembrane receptors to Nedd4 family e3 ubiquitin ligases and interact with ? arrestins. PLoS ONE. 2012;7:e50557 pubmed publisher
    ..Here we first screen all five widely-expressed human alpha arrestins for subcellular localization in ligand-stimulated and -unstimulated cells overexpressing the seven transmembrane ..
  26. Kim Y, Hofmann K, Ernst O, Scheerer P, Choe H, Sommer M. Crystal structure of pre-activated arrestin p44. Nature. 2013;497:142-6 pubmed publisher
    b>Arrestins interact with G-protein-coupled receptors (GPCRs) to block interaction with G proteins and initiate G-protein-independent signalling...
  27. Lymperopoulos A, Bathgate A. Arrestins in the cardiovascular system. Prog Mol Biol Transl Sci. 2013;118:297-334 pubmed publisher
    Of the four mammalian arrestins, only the ?-arrestins (?arrs; Arrestin2 and -3) are expressed throughout the cardiovascular system, where they regulate, as either desensitizers/internalizers or signal transducers, several G-protein-..
  28. Zhuang L, Hu W, Zhang M, Xin S, Jia W, Zhao J, et al. Beta-arrestin-1 protein represses diet-induced obesity. J Biol Chem. 2011;286:28396-402 pubmed publisher
    ..Consistently, transgenic overexpression of ?-arrestin-1 repressed diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that ?-arrestin-1 plays a role in metabolism regulation. ..
  29. Pöll F, Doll C, Schulz S. Rapid dephosphorylation of G protein-coupled receptors by protein phosphatase 1? is required for termination of ?-arrestin-dependent signaling. J Biol Chem. 2011;286:32931-6 pubmed publisher
  30. Kang D, Tian X, Benovic J. ?-Arrestins and G protein-coupled receptor trafficking. Methods Enzymol. 2013;521:91-108 pubmed publisher
    b>Arrestins are adaptor proteins that function to regulate G protein-coupled receptor (GPCR) signaling and trafficking. There are four mammalian members of the arrestin family, two visual and two nonvisual...
  31. Coffa S, Breitman M, Spiller B, Gurevich V. A single mutation in arrestin-2 prevents ERK1/2 activation by reducing c-Raf1 binding. Biochemistry. 2011;50:6951-8 pubmed publisher
    b>Arrestins regulate the signaling and trafficking of G protein-coupled receptors (GPCRs)...
  32. Liggett S. Phosphorylation barcoding as a mechanism of directing GPCR signaling. Sci Signal. 2011;4:pe36 pubmed publisher
    ..of homologous desensitization: GRK phosphorylation of the receptors leads to the subsequent binding of ?-arrestins, which partially quenches receptor coupling to G proteins...
  33. Jiang D, Xie T, Liang J, Noble P. ?-Arrestins in the immune system. Prog Mol Biol Transl Sci. 2013;118:359-93 pubmed publisher
    b>Arrestins regulate G protein-coupled receptors through receptor desensitization while also acting as signaling scaffolds to facilitate numerous effector pathways...
  34. Reiter E, Ahn S, Shukla A, Lefkowitz R. Molecular mechanism of ?-arrestin-biased agonism at seven-transmembrane receptors. Annu Rev Pharmacol Toxicol. 2012;52:179-97 pubmed publisher
    ..This review focuses on one particular class of biased ligands that has the ability to alter the balance between G protein-dependent and ?-arrestin-dependent signal transduction. ..
  35. Zheng H, Shen H, Oprea I, Worrall C, Stefanescu R, Girnita A, et al. ?-Arrestin-biased agonism as the central mechanism of action for insulin-like growth factor 1 receptor-targeting antibodies in Ewing's sarcoma. Proc Natl Acad Sci U S A. 2012;109:20620-5 pubmed publisher
    ..Defining and suppressing such biased signaling represents a practical therapeutic strategy to enhance response to anti-IGF-1R therapies. ..
  36. Girnita A, Zheng H, Gronberg A, Girnita L, Stahle M. Identification of the cathelicidin peptide LL-37 as agonist for the type I insulin-like growth factor receptor. Oncogene. 2012;31:352-65 pubmed publisher
    ..Functional experiments show that LL-37-dependent activation of the IGF-1R signaling resulted in increased migratory and invasive potential of malignant cells. ..
  37. Carpentier E, Greenbaum L, Rochdi D, Abrol R, Goddard W, Bichet D, et al. Identification and characterization of an activating F229V substitution in the V2 vasopressin receptor in an infant with NSIAD. J Am Soc Nephrol. 2012;23:1635-40 pubmed
    ..These results emphasize the importance of genetic testing and the functional characterization of mutant receptors for patients with nephrogenic syndrome of inappropriate antidiuresis because the results might inform treatment decisions. ..
  38. Lin H, Trejo J. Transactivation of the PAR1-PAR2 heterodimer by thrombin elicits ?-arrestin-mediated endosomal signaling. J Biol Chem. 2013;288:11203-15 pubmed publisher
    ..Upon thrombin activation, PAR1-PAR2 dimers co-internalize and recruit ?-arrestins to endosomes...
  39. Liu H, Long J, Zhang P, Li K, Tan J, Sun B, et al. Elevated ?-arrestin1 expression correlated with risk stratification in acute lymphoblastic leukemia. Int J Hematol. 2011;93:494-501 pubmed publisher
    ..In conclusion, ?-arrestin1 may be a useful predictor of risk stratification and prognosis of ALL, and thus of potential use in the design of individualized therapy strategies. ..
  40. Zheng H, Worrall C, Shen H, Issad T, Seregard S, Girnita A, et al. Selective recruitment of G protein-coupled receptor kinases (GRKs) controls signaling of the insulin-like growth factor 1 receptor. Proc Natl Acad Sci U S A. 2012;109:7055-60 pubmed publisher
    b>Arrestins are multifunctional proteins that play central roles in G protein-coupled receptor (GPCR) trafficking and signaling...
  41. Shukla A, Xiao K, Lefkowitz R. Emerging paradigms of ?-arrestin-dependent seven transmembrane receptor signaling. Trends Biochem Sci. 2011;36:457-69 pubmed publisher
    b>Arrestins, originally discovered to desensitize activated seven transmembrane receptors (7TMRs; also known as G-protein-coupled receptors, GPCRs), are now well established mediators of receptor endocytosis, ubiquitylation and G protein-..
  42. Law I, Murphy J, Bakirtzi K, Bunnett N, Pothoulakis C. Neurotensin-induced proinflammatory signaling in human colonocytes is regulated by ?-arrestins and endothelin-converting enzyme-1-dependent endocytosis and resensitization of neurotensin receptor 1. J Biol Chem. 2012;287:15066-75 pubmed publisher
    ..Our results also indicate that ?ARRs and ECE-1-dependent recycling regulate MAP kinase and NF-?B signaling as well as cell proliferation in human colonocytes in response to NT. ..
  43. Mustafa S, See H, Seeber R, Armstrong S, White C, Ventura S, et al. Identification and profiling of novel ?1A-adrenoceptor-CXC chemokine receptor 2 heteromer. J Biol Chem. 2012;287:12952-65 pubmed publisher
    ..This has important implications for the use and future development of pharmaceuticals targeting these receptors...
  44. Lymperopoulos A. Beta-arrestin biased agonism/antagonism at cardiovascular seven transmembrane-spanning receptors. Curr Pharm Des. 2012;18:192-8 pubmed
    ..Additionally, the discovery of this novel mode of heptahelical receptor signaling via ?arrestins has prompted a revision of classical pharmacological concepts such as receptor agonism/antagonism, as well as ..
  45. Allen J, Yost J, Setola V, Chen X, Sassano M, Chen M, et al. Discovery of ?-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc Natl Acad Sci U S A. 2011;108:18488-93 pubmed publisher
    ..Recent work has highlighted noncanonical modes of dopamine D(2) receptor (D(2)R) signaling via ?-arrestins as being important for the therapeutic actions of both antipsychotic and antimanic agents...
  46. Krilov L, Nguyen A, Miyazaki T, Unson C, Williams R, Lee N, et al. Dual mode of glucagon receptor internalization: role of PKC?, GRKs and ?-arrestins. Exp Cell Res. 2011;317:2981-94 pubmed publisher
    ..The present study explores the mechanisms of GR internalization and the role of PKC?, GPCR kinases (GRKs) and ?-arrestins therein. We have reported previously that PKC? mediates GR phosphorylation and desensitization...
  47. Yang X, Zhou G, Ren T, Li H, Zhang Y, Yin D, et al. ?-Arrestin prevents cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt pathways. Apoptosis. 2012;17:1019-26 pubmed publisher
    ..Our study thus demonstrates that ?-arrestin inhibits cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt signaling pathways. ..
  48. Zhuang L, Hu W, Xin S, Zhao J, Pei G. Beta-arrestin-1 protein represses adipogenesis and inflammatory responses through its interaction with peroxisome proliferator-activated receptor-gamma (PPARgamma). J Biol Chem. 2011;286:28403-13 pubmed publisher
    ..Therefore, our findings not only reveal a molecular mechanism for the modulation of obesity by ?-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders. ..
  49. Oligny Longpré G, Corbani M, Zhou J, Hogue M, Guillon G, Bouvier M. Engagement of ?-arrestin by transactivated insulin-like growth factor receptor is needed for V2 vasopressin receptor-stimulated ERK1/2 activation. Proc Natl Acad Sci U S A. 2012;109:E1028-37 pubmed publisher
    ..Here, we describe a G protein-independent mechanism that unravels an unanticipated role for ?-arrestins. Stimulation of the V2 vasopressin receptor (V2R) in cultured cells or in vivo in rat kidney medullar collecting ..
  50. 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
    ..three families of proteins: the heterotrimeric G proteins, the G-protein-coupled receptor kinases (GRKs) and the arrestins. G proteins mediate activation of second-messenger-generating enzymes and other effectors, GRKs phosphorylate ..
  51. Shenoy S, Lefkowitz R. ?-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci. 2011;32:521-33 pubmed publisher
    b>Arrestins function as endocytic adaptors and mediate trafficking of a variety of cell-surface receptors, including seven-transmembrane receptors (7TMRs)...
  52. Soh U, Trejo J. Activated protein C promotes protease-activated receptor-1 cytoprotective signaling through ?-arrestin and dishevelled-2 scaffolds. Proc Natl Acad Sci U S A. 2011;108:E1372-80 pubmed publisher
    ..In human endothelial cells, PAR1 and ?-arrestins form a preassembled complex and cosegregate in caveolin-1-enriched fractions...
  53. Lundgren K, Tobin N, Lehn S, Stal O, Rydén L, Jirstrom K, et al. Stromal expression of ?-arrestin-1 predicts clinical outcome and tamoxifen response in breast cancer. J Mol Diagn. 2011;13:340-51 pubmed publisher
    ..Furthermore, CCND1 amplification was inversely correlated with tumor cell expression of ?-arrestin-1, indicating ARRB1 gene deletion in CCND1-amplified breast cancers. ..