arrestins

Summary

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

Top Publications

  1. pmc Teaching old receptors new tricks: biasing seven-transmembrane receptors
    Sudarshan Rajagopal
    Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina 27710, USA
    Nat Rev Drug Discov 9:373-86. 2010
  2. ncbi Beta-arrestins and cell signaling
    Scott M DeWire
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Physiol 69:483-510. 2007
  3. ncbi Transduction of receptor signals by beta-arrestins
    Robert J Lefkowitz
    Howard Hughes Medical Institute, Durham, NC 27710, USA
    Science 308:512-7. 2005
  4. ncbi An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior
    Jean Martin Beaulieu
    Department of Cell Biology, Center for Models of Human Disease, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina 27710, USA
    Cell 122:261-73. 2005
  5. pmc Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling
    Arun K Shukla
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Trends Biochem Sci 36:457-69. 2011
  6. ncbi Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes
    L M Luttrell
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 283:655-61. 1999
  7. pmc β-Arrestin-mediated receptor trafficking and signal transduction
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Trends Pharmacol Sci 32:521-33. 2011
  8. pmc Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds
    L M Luttrell
    The Geriatrics Research, Education and Clinical Center, Durham Veterans Affairs Medical Center, Durham, NC 27705, USA
    Proc Natl Acad Sci U S A 98:2449-54. 2001
  9. ncbi Regulation of receptor trafficking by GRKs and arrestins
    Catherine A C Moore
    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Annu Rev Physiol 69:451-82. 2007
  10. ncbi Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4
    Wei Chen
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Science 301:1391-4. 2003

Detail Information

Publications313 found, 100 shown here

  1. pmc Teaching old receptors new tricks: biasing seven-transmembrane receptors
    Sudarshan Rajagopal
    Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Durham, North Carolina 27710, USA
    Nat Rev Drug Discov 9:373-86. 2010
    ..Originally identified as mediators of 7TMR desensitization, beta-arrestins (arrestin 2 and arrestin 3) are now recognized as true adaptor proteins that transduce signals to multiple ..
  2. ncbi Beta-arrestins and cell signaling
    Scott M DeWire
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Physiol 69:483-510. 2007
    Upon their discovery, beta-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization...
  3. ncbi Transduction of receptor signals by beta-arrestins
    Robert J Lefkowitz
    Howard Hughes Medical Institute, Durham, NC 27710, USA
    Science 308:512-7. 2005
    ..scaffolding of cytoplasmic signaling complexes via two multifunctional adaptor and transducer molecules, beta-arrestins 1 and 2...
  4. ncbi An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior
    Jean Martin Beaulieu
    Department of Cell Biology, Center for Models of Human Disease, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina 27710, USA
    Cell 122:261-73. 2005
    ....
  5. pmc Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling
    Arun K Shukla
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Trends Biochem Sci 36:457-69. 2011
    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 ..
  6. ncbi Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes
    L M Luttrell
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 283:655-61. 1999
    ....
  7. pmc β-Arrestin-mediated receptor trafficking and signal transduction
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Trends Pharmacol Sci 32:521-33. 2011
    b>Arrestins function as endocytic adaptors and mediate trafficking of a variety of cell-surface receptors, including seven-transmembrane receptors (7TMRs)...
  8. pmc Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds
    L M Luttrell
    The Geriatrics Research, Education and Clinical Center, Durham Veterans Affairs Medical Center, Durham, NC 27705, USA
    Proc Natl Acad Sci U S A 98:2449-54. 2001
    Using both confocal immunofluorescence microscopy and biochemical approaches, we have examined the role of beta-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of ..
  9. ncbi Regulation of receptor trafficking by GRKs and arrestins
    Catherine A C Moore
    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Annu Rev Physiol 69:451-82. 2007
    ..In this chapter we discuss the mechanisms that regulate receptor endocytic trafficking, emphasizing the role of GPCR kinases (GRKs) and arrestins in this process.
  10. ncbi Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4
    Wei Chen
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Science 301:1391-4. 2003
    ..These findings provide a previously unrecognized mechanism for receptor recruitment of beta-arrestin and demonstrate that Dvl plays an important role in the endocytosis of frizzled, as well as in promoting signaling...
  11. ncbi beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor
    Sudha K Shenoy
    Howard Hughes Medical Institute at Duke University Medical Center, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 281:1261-73. 2006
    ..Here we demonstrate a novel signaling mechanism wherein beta-arrestins mediate beta2AR signaling to extracellular-signal regulated kinases 1/2 (ERK 1/2) independent of G protein ..
  12. pmc Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:22166-76. 2008
    ..Collectively, our findings indicate that the degradative fate of the beta(2)AR in the lysosomal compartments is dependent upon beta-arrestin2-mediated recruitment of Nedd4 to the activated receptor and Nedd4-catalyzed ubiquitination...
  13. ncbi Physiological roles of G protein-coupled receptor kinases and arrestins
    Richard T Premont
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Physiol 69:511-34. 2007
    ..This review focuses on the physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders as well as on recent studies using knockout and transgenic mice to explore the role of GRK-..
  14. ncbi Beta-arrestin/Ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells
    Timothy T Li
    Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada
    Mol Cancer Res 7:1064-77. 2009
    ..Thus, our data show a novel role for beta-arrestin/Ral signaling in mediating LPA-induced breast cancer cell migration and invasion, two important processes in metastasis...
  15. pmc An expanded family of arrestins regulate metabolism
    Parth Patwari
    Harvard Stem Cell Institute and the Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Cambridge, MA 02139, USA
    Trends Endocrinol Metab 23:216-22. 2012
    The classical visual and β-arrestins belong to a larger family of proteins that likely share structural similarity. Humans have an additional six related proteins sometimes termed the α-arrestins, whose functions are now emerging...
  16. ncbi GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling
    Eric Reiter
    Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Trends Endocrinol Metab 17:159-65. 2006
    ..two other families of protein have this remarkable characteristic: G-protein-coupled receptor kinases and beta-arrestins. These two protein families have long been known to have a central and coordinated role in the "..
  17. pmc beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha
    D Scott Witherow
    Department of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 101:8603-7. 2004
    In addition to their roles in desensitization and signaling of seven-membrane-spanning receptors, beta-arrestins have been more recently implicated in regulating non-seven-membrane-spanning receptor pathways...
  18. ncbi Classical and new roles of beta-arrestins in the regulation of G-protein-coupled receptors
    K L Pierce
    The Howard Hughes Medical Institute and the Departments of Medicine and Biochemistry, Box 3821, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Rev Neurosci 2:727-33. 2001
    In the classical model of G-protein-coupled receptor (GPCR) regulation, arrestins terminate receptor signalling...
  19. pmc Antagonism of dopamine D2 receptor/beta-arrestin 2 interaction is a common property of clinically effective antipsychotics
    Bernard Masri
    Departments of Cell Biology, Medicine and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 105:13656-61. 2008
    ..Thus, selective targeting of D2(L)R/beta-arrestin 2 interaction and related signaling pathways may provide new opportunities for antipsychotic development...
  20. ncbi AMD3100 is a CXCR7 ligand with allosteric agonist properties
    Irina Kalatskaya
    Department of Biochemistry, Universite de Montreal, Montreal, Quebec, Canada
    Mol Pharmacol 75:1240-7. 2009
    ....
  21. pmc Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2
    Huijun Wei
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 100:10782-7. 2003
    ..These findings imply the existence of independent G protein- and beta-arrestin 2-mediated pathways leading to ERK1/2 activation and the existence of distinct "active" conformations of a seven-membrane-spanning receptor coupled to each...
  22. ncbi Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins
    Claire Jacob
    Department of Surgery, University of California, San Francisco, California 94143, USA
    J Biol Chem 280:31936-48. 2005
    ..This was prevented by a tryptase inhibitor. We determined the role of ERK1/2 and of beta-arrestins, which recruit ERK1/2 to PAR2 in endosomes and retain ERK1/2 in the cytosol, on PAR2-mediated alterations in ..
  23. pmc G protein-coupled receptor sorting to endosomes and lysosomes
    Adriano Marchese
    Department of Pharmacology and Experimental Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
    Annu Rev Pharmacol Toxicol 48:601-29. 2008
    ..Several recent studies also indicate that the covalent modification of GPCRs with ubiquitin serves as a signal for internalization and lysosomal sorting, expanding the diversity of mechanisms that control trafficking of mammalian GPCRs...
  24. ncbi Beta-arrestins as regulators of signal termination and transduction: how do they determine what to scaffold?
    Kathryn A DeFea
    Biomedical Sciences Division, University of California Riverside, CA 92521, USA
    Cell Signal 23:621-9. 2011
    Over the last decade β-arrestins have emerged as pleiotropic scaffold proteins, capable of mediating numerous diverse responses to multiple agonists...
  25. pmc Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors
    Mounia Azzi
    Department of Biochemistry, Universite de Montreal, Montreal, QC, Canada H3C 3J7
    Proc Natl Acad Sci U S A 100:11406-11. 2003
    ..These results point to a multistate model of receptor activation in which ligand-specific conformations are capable of differentially activating distinct signaling partners...
  26. pmc Distinct phosphorylation sites on the β(2)-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin
    Kelly N Nobles
    1Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Sci Signal 4:ra51. 2011
    ..plays essential roles in the regulation of receptor function by promoting interactions of the receptors with β-arrestins. These multifunctional adaptor proteins desensitize GPCRs, by reducing receptor coupling to G proteins and ..
  27. ncbi GRKs and arrestins: regulators of migration and inflammation
    Anne Vroon
    Department of Psychoneuroimmunology, Room KC03 063 0, Lundlaan 6, 3584 EA, Utrecht, The Netherlands
    J Leukoc Biol 80:1214-21. 2006
    ..GPCR kinases (GRKs) and arrestins control GPCR signaling by mediating desensitization and thus, regulating further signal propagation through G ..
  28. ncbi Desensitization of G protein-coupled receptors and neuronal functions
    Raul R Gainetdinov
    Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Neurosci 27:107-44. 2004
    ..Phosphorylated receptors are then bound by arrestins, which prevent further stimulation of G proteins and downstream signaling pathways...
  29. ncbi Enhanced morphine analgesia in mice lacking beta-arrestin 2
    L M Bohn
    Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 286:2495-8. 1999
    ..Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence...
  30. pmc Temporal profiling of orexin receptor-arrestin-ubiquitin complexes reveals differences between receptor subtypes
    Matthew B Dalrymple
    Laboratory for Molecular Endocrinology G Protein Coupled Receptors, Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Perth, Western Australia 6009, Australia
    J Biol Chem 286:16726-33. 2011
    ..classified as class B receptors for β-arrestin usage based on the initial strength of interaction with both β-arrestins, our temporal profiling revealed tangible differences between OxR subtypes...
  31. ncbi Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly
    Melissa A Edeling
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom
    Dev Cell 10:329-42. 2006
    ..Another interaction surface on the beta2 appendage sandwich is identified for proteins such as eps15 and clathrin, suggesting a mechanism by which clathrin displaces eps15 to lattice edges during assembly...
  32. pmc Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling
    Sudha K Shenoy
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Biochem J 375:503-15. 2003
    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...
  33. pmc Application of G protein-coupled receptor-heteromer identification technology to monitor β-arrestin recruitment to G protein-coupled receptor heteromers
    Heng B See
    Laboratory for Molecular Endocrinology GPCRs, Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Hospital Avenue, Nedlands, WA 6009, Australia
    Assay Drug Dev Technol 9:21-30. 2011
    ....
  34. pmc Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection
    Takahisa Noma
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Clin Invest 117:2445-58. 2007
    ..Here, we identify a new signaling mechanism using both in vitro and in vivo systems whereby beta-arrestins mediate beta1AR signaling to the EGFR...
  35. pmc Therapeutic potential of β-arrestin- and G protein-biased agonists
    Erin J Whalen
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Trends Mol Med 17:126-39. 2011
    ..It is now appreciated that β-arrestins, once viewed simply as negative regulators of traditional 7TMR-stimulated G protein signaling, act as ..
  36. pmc Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling
    John M Busillo
    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 285:7805-17. 2010
    ..These studies reveal that site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases resulting in both positive and negative modulation of CXCR4 signaling...
  37. pmc Location, location, location...site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling
    Andrew B Tobin
    Department of Cell Physiology and Pharmacology, University of Leicester, LE1 9HN, UK
    Trends Pharmacol Sci 29:413-20. 2008
    ..receptors (GPCRs) are regulated by phosphorylation in a process that results in the recruitment of arrestins, leading to receptor desensitization and the activation of arrestin-dependent processes...
  38. ncbi Beta-arrestin-biased ligands at seven-transmembrane receptors
    Jonathan D Violin
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Trends Pharmacol Sci 28:416-22. 2007
    ..receptors (7TMRs), the most common molecular targets of modern drug therapy, are critically regulated by beta-arrestins, which both inhibit classic G-protein signaling and initiate distinct beta-arrestin signaling...
  39. ncbi G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization
    R J Lefkowitz
    Departments of Medicine Cardiology and Biochemistry, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 273:18677-80. 1998
  40. pmc beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2
    K A Defea
    Department of Surgery, University of California, San Francisco, San Francisco, California 94143 0660, USA
    J Cell Biol 148:1267-81. 2000
    ....
  41. pmc On the origins of arrestin and rhodopsin
    Carlos E Alvarez
    Center for Molecular and Human Genetics, The Research Institute at Nationwide Children s Hospital, Columbus, OH 43205, USA
    BMC Evol Biol 8:222. 2008
    ..GPCRs are intimately associated with trimeric G proteins, G protein receptor kinases, and arrestins. We conducted phylogenetic studies to reconstruct the history of arrestins...
  42. ncbi New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors
    Robert J Lefkowitz
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell 24:643-52. 2006
    beta-arrestins, originally discovered as molecules that bind to and desensitize the activated and phosphorylated form of the G protein-coupled beta2-adrenergic receptor (beta2-AR), have recently emerged as multifunctional adaptor/..
  43. pmc G protein-dependent and G protein-independent signaling pathways and their impact on cardiac function
    Douglas G Tilley
    Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, and Center for Translational Medicine, Thomas Jefferson University, 1025 Walnut Street, 402 College Building, Philadelphia, PA 19107, USA
    Circ Res 109:217-30. 2011
    ....
  44. ncbi Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation
    M Han
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Structure 9:869-80. 2001
    b>Arrestins are responsible for the desensitization of many sequence-divergent G protein-coupled receptors...
  45. pmc G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor
    Yoon Namkung
    Molecular Neuropharmacology Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892 9405, USA
    J Biol Chem 284:15038-51. 2009
    ..In contrast, if the receptor is highly phosphorylated, then receptor recycling is promoted. These results reveal a novel role for GRK-mediated phosphorylation in regulating the post-endocytic trafficking of a G protein-coupled receptor...
  46. pmc Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways
    Jeffrey J Kovacs
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Dev Cell 17:443-58. 2009
    b>Arrestins were identified as mediators of G protein-coupled receptor (GPCR) desensitization and endocytosis...
  47. ncbi Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways
    Hua Gao
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, People s Republic of China
    Mol Cell 14:303-17. 2004
    ..Taken together, the current study may present a novel mechanism for regulation of the immune system by the sympathetic nervous system...
  48. pmc β-Arrestin-biased agonism as the central mechanism of action for insulin-like growth factor 1 receptor-targeting antibodies in Ewing's sarcoma
    Huiyuan Zheng
    Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden
    Proc Natl Acad Sci U S A 109:20620-5. 2012
    ..Defining and suppressing such biased signaling represents a practical therapeutic strategy to enhance response to anti-IGF-1R therapies...
  49. pmc Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins
    Parth Patwari
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA
    J Biol Chem 284:24996-5003. 2009
    ..Txnip is a member of the alpha-arrestin protein family; the alpha-arrestins are related to the classical beta-arrestins and visual arrestins...
  50. ncbi Differential beta-arrestin trafficking and endosomal sorting of somatostatin receptor subtypes
    Giovanni Tulipano
    Institut fur Pharmakologie und Toxikologie, Otto von Guericke Universitat, Leipziger Strasse 44, 39120 Magdeburg, Germany
    J Biol Chem 279:21374-82. 2004
    ..Together, these findings may provide important clues about the regulation of receptor responsiveness during long-term administration of somatostatin analogs...
  51. pmc Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia
    E R Bychkov
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Neurobiol Aging 29:379-96. 2008
    b>Arrestins and G proteins-coupled receptor kinases (GRKs) regulate signaling and trafficking of G protein-coupled receptors...
  52. ncbi G protein coupled receptor transactivation: extending the paradigm to include serine/threonine kinase receptors
    Micah L Burch
    BakerIDI Heart and Diabetes Institute, Commercial Road, Melbourne, Victoria 3004, Australia
    Int J Biochem Cell Biol 44:722-7. 2012
    ..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...
  53. ncbi The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits
    S A Laporte
    Howard Hughes Medical Institute Laboratories and the Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 275:23120-6. 2000
    Beta-arrestins are cytosolic proteins that regulate the signaling and the internalization of G protein-coupled receptors (GPCRs)...
  54. pmc Neurotensin triggers dopamine D2 receptor desensitization through a protein kinase C and beta-arrestin1-dependent mechanism
    Dominic Thibault
    Department of Pharmacology, Faculty of Medicine, Universite de Montreal, Quebec H3C 3J7, Canada
    J Biol Chem 286:9174-84. 2011
    ..Taken together, our data suggest that NT acutely regulates D2 autoreceptor function and DA neuron excitability through PKC-mediated phosphorylation of the D2R, leading to heterologous receptor desensitization...
  55. pmc The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis
    S A Laporte
    Howard Hughes Medical Institute Laboratories and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 96:3712-7. 1999
    ..These findings point to a role for AP-2 in GPCR endocytosis, and they suggest that AP-2 functions as a clathrin adaptor for the endocytosis of diverse classes of membrane receptors...
  56. ncbi Clozapine and lithium require Caenorhabditis elegans β-arrestin and serum- and glucocorticoid-inducible kinase to affect Daf-16 (FOXO) localization
    Kathrine R Weeks
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana 71130 3932, USA
    J Neurosci Res 89:1658-65. 2011
    ..Lithium, a mood stabilizer often used to treat psychosis, also requires β-arrestin and SGK to suppress the nuclear localization of DAF-16...
  57. pmc Identification and profiling of novel α1A-adrenoceptor-CXC chemokine receptor 2 heteromer
    Sanam Mustafa
    Laboratory for Molecular Endocrinology G Protein Coupled Receptors, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, Western Australia 6009, Australia
    J Biol Chem 287:12952-65. 2012
    ..This has important implications for the use and future development of pharmaceuticals targeting these receptors...
  58. pmc beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins
    W Chen
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 98:14889-94. 2001
    One aspect of the function of the beta-arrestins is to serve as scaffold or adapter molecules coupling G-protein coupled receptors (GPCRs) to signal transduction pathways distinct from traditional second messenger pathways...
  59. ncbi Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling
    S S Ferguson
    The John P Robarts Research Institute and Department of Physiology, University of Western Ontario, London, Ontario, Canada
    Pharmacol Rev 53:1-24. 2001
    ..GRK-mediated receptor phosphorylation promotes the binding of beta-arrestins, which not only uncouple receptors from heterotrimeric G proteins but also target many GPCRs for internalization ..
  60. pmc Β-arrestin: a signaling molecule and potential therapeutic target for heart failure
    Nabila Noor
    Duke University School of Medicine, Durham, NC, USA
    J Mol Cell Cardiol 51:534-41. 2011
    ..This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."..
  61. pmc Activated protein C promotes protease-activated receptor-1 cytoprotective signaling through β-arrestin and dishevelled-2 scaffolds
    Unice J K Soh
    Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:E1372-80. 2011
    ..In human endothelial cells, PAR1 and β-arrestins form a preassembled complex and cosegregate in caveolin-1-enriched fractions...
  62. pmc Selective recruitment of G protein-coupled receptor kinases (GRKs) controls signaling of the insulin-like growth factor 1 receptor
    Huiyuan Zheng
    Department of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden
    Proc Natl Acad Sci U S A 109:7055-60. 2012
    b>Arrestins are multifunctional proteins that play central roles in G protein-coupled receptor (GPCR) trafficking and signaling...
  63. ncbi Heteromerization of angiotensin receptors changes trafficking and arrestin recruitment profiles
    Enzo R Porrello
    Department of Physiology, The University of Melbourne, Victoria 3010, Australia
    Cell Signal 23:1767-76. 2011
    ....
  64. pmc Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy
    John A Allen
    Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 108:18488-93. 2011
    ..Recent work has highlighted noncanonical modes of dopamine D(2) receptor (D(2)R) signaling via β-arrestins as being important for the therapeutic actions of both antipsychotic and antimanic agents...
  65. ncbi beta-arrestin-biased agonism at the beta2-adrenergic receptor
    Matthew T Drake
    Departments of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:5669-76. 2008
    ..unclear if among beta 2AR agonists there exist ligands that disproportionately signal via G proteins or beta-arrestins and are hence "biased...
  66. pmc beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi
    George S Baillie
    Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute for Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Proc Natl Acad Sci U S A 100:940-5. 2003
    ..beta-Arrestins recruit the cAMP-degrading PDE4 phosphodiesterases to the beta(2)AR, thus controlling PKA activity at the ..
  67. ncbi Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2
    Wei Chen
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 306:2257-60. 2004
    ..A Smo agonist stimulated and a Smo antagonist (cyclopamine) inhibited both phosphorylation of Smo by GRK2 and interaction of beta-arrestin 2 with Smo. beta-Arrestin 2 and GRK2 are thus potential mediators of signaling by activated Smo...
  68. pmc Regulation of smoothened by Drosophila G-protein-coupled receptor kinases
    Shuofei Cheng
    Institut de Recherches Cliniques de Montreal, 110 Pine Avenue West, Montreal, QC H2W1R7, Canada
    Dev Biol 337:99-109. 2010
    ..G-protein-coupled receptor kinase activity is also important for efficient downstream signaling...
  69. ncbi Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization
    Moshmi Bhattacharya
    Cell Biology Research Group, The John P Robarts Research Institute, The University of Western Ontario, 100 Perth Drive, London, Ontario, N6A 5K8, Canada
    Nat Cell Biol 4:547-55. 2002
    beta-Arrestins are important in chemoattractant receptor-induced granule release, a process that may involve Ral-dependent regulation of the actin cytoskeleton...
  70. ncbi Identification of novel species-selective agonists of the G-protein-coupled receptor GPR35 that promote recruitment of β-arrestin-2 and activate Gα13
    Laura Jenkins
    Molecular Pharmacology Group, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Biochem J 432:451-9. 2010
    ..The ligands identified in these studies will be useful in interrogating the biological actions of GPR35, but appreciation of the species selectivity of ligands at this receptor will be vital to correctly attribute function...
  71. pmc ARRB1-mediated regulation of E2F target genes in nicotine-induced growth of lung tumors
    Piyali Dasgupta
    Department of Oncologic Sciences, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
    J Natl Cancer Inst 103:317-33. 2011
    ..However, whether ARRB1 translocates to the nucleus upon nicotinic acetylcholine receptor activation and how it regulates growth of human NSCLCs are not known...
  72. ncbi Real-time monitoring of ubiquitination in living cells by BRET
    Julie Perroy
    Département de Biochimie and Groupe de Recherche sur le Système Nerveux Autonome, Universite de Montreal, C P 6128 Succursale Centre Ville Montréal, Quebec H3C 3J7, Canada
    Nat Methods 1:203-8. 2004
    ..The ubiquitination BRET assay should prove to be a useful tool for studying the dynamic ubiquitination of proteins and for understanding which cellular functions are regulated by this post-translational event...
  73. pmc A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling
    James W Wisler
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 104:16657-62. 2007
    ..We hypothesize that such signaling may contribute to the special efficacy of carvedilol in the treatment of heart failure and may serve as a prototype for a new generation of therapeutic beta2AR ligands...
  74. pmc Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction
    K DeFea
    Biomedical Sciences Division, University of California, Riverside, 1620 Computer Statistics Bldg, Riverside, CA 92521, USA
    Br J Pharmacol 153:S298-309. 2008
    ..Recently, GPCRs have been demonstrated to elicit signals through interaction with the scaffolding proteins, beta-arrestins-1 and 2, independent of heterotrimeric G-protein coupling...
  75. ncbi The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals
    Louis M Luttrell
    The Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Sci 115:455-65. 2002
    beta-Arrestins are versatile adapter proteins that form complexes with most G-protein-coupled receptors (GPCRs) following agonist binding and phosphorylation of receptors by G-protein-coupled receptor kinases (GRKs)...
  76. pmc {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation
    Seungkirl Ahn
    Departments of Medicine and Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:8855-65. 2009
    beta-Arrestins, originally discovered as terminators of G protein-coupled receptor signaling, have more recently been appreciated to also function as signal transducers in their own right, although the consequences for cellular ..
  77. ncbi Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation
    Cornelius Krasel
    Institute for Pharmacology and Toxicology, Versbacher Strasse 9, D 97078 Wurzburg, Germany
    J Biol Chem 280:9528-35. 2005
    ..of the agonist-stimulated receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by binding of beta-arrestins to the phosphorylated receptor...
  78. pmc The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42
    Karthikeyan Mythreye
    Department of Medicine and Pharmacology, Duke University Medical Center, Durham, NC 27708, USA
    Proc Natl Acad Sci U S A 106:8221-6. 2009
    ..These studies identify a TGF-beta independent homeostatic function for TbetaRIII in regulating cell migration...
  79. pmc ARRDC3 suppresses breast cancer progression by negatively regulating integrin beta4
    K M Draheim
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Oncogene 29:5032-47. 2010
    ..The results identify the ARRCD3-ITGbeta4 pathway as a new therapeutic target in breast cancer and show the importance of connecting genetic arrays with mechanistic studies in the search for new treatments...
  80. ncbi A beta-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation
    L S Barak
    Howard Hughes Medical Institute Laboratories and Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 272:27497-500. 1997
    ..is a convergent step of GPCR signaling, increase by 5-fold the number of GPCRs known to interact with beta-arrestins, demonstrate that the cytosol is the predominant reservoir of biologically active beta-arrestins, and provide ..
  81. pmc kurtz, a novel nonvisual arrestin, is an essential neural gene in Drosophila
    G Roman
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genetics 155:1281-95. 2000
    ..Importantly, the expression of a full-length krz cDNA within the CNS rescues the krz(1) lethality. These experiments establish the krz nonvisual arrestin as an essential neural gene in Drosophila...
  82. ncbi Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling
    Yaya Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Nat Immunol 7:139-47. 2006
    ..Here we show that beta-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR-IL-1R activation...
  83. pmc Role of beta-arrestin 1 in the metastatic progression of colorectal cancer
    F Gregory Buchanan
    Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, 661 PRB, 2220 Pierce Avenue, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 103:1492-7. 2006
    ..Furthermore, our data implicate a functional role for beta-arrestin 1 as a mediator of cellular migration and metastasis...
  84. pmc Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of extracellular signal-regulated kinase and β-arrestin2 with antinociceptive activity
    Pingwei Zhao
    Department of Anatomy and Cell Biology, Center for Substance Abuse Research, Temple University School of Medicine, 3420 North Broad St, Philadelphia, PA 19140, USA
    Mol Pharmacol 78:560-8. 2010
    ..Our results indicate that the unexpected biological functions of pamoic acid may yield potential new uses for a common drug constituent...
  85. pmc beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice
    Robert W Walters
    Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
    J Clin Invest 119:1312-21. 2009
    ..the GPCR GPR109A and Gi/Go proteins, here we dissected the roles of G proteins and the adaptor proteins, beta-arrestins, in nicotinic acid-induced signaling and physiological responses...
  86. pmc Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands
    Ankur Kapur
    Department of Anatomy and Cell Biology and Center for Substance Abuse Research, Temple University, Philadelphia, Pennsylvania 19140, USA
    J Biol Chem 284:29817-27. 2009
    ..The activation of GPR55 by rimonabant may be responsible for some of the off-target effects that led to its removal as a potential obesity therapy...
  87. pmc Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes
    Keshava Rajagopal
    Department of Surgery, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:16284-9. 2006
    The G protein-coupled receptor kinases (GRKs) and beta-arrestins, families of molecules essential to the desensitization of G protein-dependent signaling via seven-transmembrane receptors (7TMRs), have been recently shown to also ..
  88. pmc Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling
    Karl Balabanian
    INSERM U819, Paris, France
    J Clin Invest 118:1074-84. 2008
    ..Taken together, these results have revealed a pivotal role for GRK3 in regulating CXCR4 attenuation and have provided a mechanistic link between the GRK3 pathway and the CXCR4-related WHIM(WT) disorder...
  89. pmc Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR)
    Kunhong Xiao
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 107:15299-304. 2010
    ..This study provides a system-based view of beta-arrestin-mediated phosphorylation events downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR signaling...
  90. pmc beta-Arrestin mediates beta1-adrenergic receptor-epidermal growth factor receptor interaction and downstream signaling
    Douglas G Tilley
    Department of Medicine, Duke University, Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:20375-86. 2009
    ..These data reveal a new signaling paradigm in which beta-arrestin is required for the maintenance of a beta1AR-EGFR interaction that can direct cytosolic targeting of ERK in response to catecholamine stimulation...
  91. ncbi beta-arrestins: traffic cops of cell signaling
    Robert J Lefkowitz
    Howard Hughes Medical Institute, Duke University Medical Center, DUMC Box 3821, Durham, NC 27710, USA
    Curr Opin Cell Biol 16:162-8. 2004
    ..These functions reflect the ability of the beta-arrestins to bind an ever-growing list of signaling and endocytic elements, often in an agonist-dependent fashion...
  92. ncbi Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor
    Seungkirl Ahn
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:35518-25. 2004
    ..Such differential regulation of the temporal and spatial patterns of ERK1/2 activation via these two pathways strongly implies the existence of distinct physiological endpoints...
  93. ncbi {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
    Leonard Girnita
    Department of Oncology and Pathology, Division of Cellular and Molecular Tumor Pathology, Cancer Center Karolinska, R8 04, Karolinska Hospital, SE 171 76 Stockholm, Sweden
    J Biol Chem 280:24412-9. 2005
    ..To our knowledge this is the first study demonstrating a defined molecular role of beta-arrestin with direct relevance to cell growth and cancer...
  94. pmc Beta-arrestin-2 regulates the development of allergic asthma
    Julia K L Walker
    Department of Medicine, Duke University Medical Center, Box 3821, Durham, North Carolina 27710, USA
    J Clin Invest 112:566-74. 2003
    ..Because beta-arrestin-2 regulates the development of allergic inflammation at a proximal step in the inflammatory cascade, novel therapies focused on this protein may prove useful in the treatment of asthma...
  95. pmc Identification of betaArrestin2 as a corepressor of androgen receptor signaling in prostate cancer
    Vijayabaskar Lakshmikanthan
    Department of Pathology, Medical College of Georgia, Augusta, GA 30912, USA
    Proc Natl Acad Sci U S A 106:9379-84. 2009
    ..We conclude that betaArrestin2 acts as a corepressor of AR by serving as a scaffold for Mdm2 leading to the AR ubiquitylation and degradation...
  96. pmc Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice
    Alan M Fong
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 99:7478-83. 2002
    ..examined signaling and chemotactic responses in splenocytes derived from knockout mice deficient in various beta-arrestins and GRKs, with the expectation that these responses might be enhanced...
  97. pmc Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7
    Sudarshan Rajagopal
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 107:628-32. 2010
    ..It is now recognized that 7TMRs also signal through beta-arrestins, which act as versatile adapters controlling receptor signaling, desensitization, and trafficking...
  98. pmc Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling
    Jihee Kim
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 102:1442-7. 2005
    beta-arrestins bind to G protein-coupled receptor kinase (GRK)-phosphorylated seven transmembrane receptors, desensitizing their activation of G proteins, while concurrently mediating receptor endocytosis, and some aspects of receptor ..
  99. pmc Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor
    Xiu Rong Ren
    Department of Biochemistry, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 102:1448-53. 2005
    Signaling through beta-arrestins is a recently appreciated mechanism used by seven-transmembrane receptors...
  100. ncbi Morphine side effects in beta-arrestin 2 knockout mice
    Kirsten M Raehal
    Department of Pharmacology and Psychiatry, Ohio State University College of Medicine, Columbus, 43210 1239, USA
    J Pharmacol Exp Ther 314:1195-201. 2005
    ..Surprisingly, the genetic disruption of opioid receptor regulation, while enhancing and prolonging analgesia, dramatically attenuates the respiratory suppression and acute constipation caused by morphine...
  101. ncbi Dysfunction of endothelium-dependent relaxation to insulin via PKC-mediated GRK2/Akt activation in aortas of ob/ob mice
    Kumiko Taguchi
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa ku, Tokyo, Japan
    Am J Physiol Heart Circ Physiol 301:H571-83. 2011
    ....

Research Grants66

  1. H1R Signaling and Immune Deviation in EAE
    Cory Teuscher; Fiscal Year: 2013
    ..For many GPCRs sustained MAPK activation involves non-G-protein signaling through b-arrestins. Since we found no difference in G-protein activation of allelic H1R-Ga fusion proteins, this suggested that H1R ..
  2. Regulation and Function of Urocortins and their Receptors
    Aditi Bhargava; Fiscal Year: 2013
    ..We will explore the ability of the adaptor/scaffolding proteins ([unreadable]-arrestins and dynamin) to desensitize and resensitize CRFRs...
  3. The Role of Beta-Arrestins 1 and 2 in Rheumatoid Arthritis
    Hongkuan Fan; Fiscal Year: 2010
    ..Once the specific immune cells that exhibit altered expression of -arrestins are identified, the role of -arrestin 1 and 2 expression on activation of these cells will be examined using the ..
  4. REGULATION OF CELLULAR RESPONSES TO NEUROPEPTIDES
    Nigel W Bunnett; Fiscal Year: 2010
    ..The role of p-arrestins, Rabs and the cytoskeleton in NKlR-mediated MAP kinase activation will be determined using reagents developed in ..
  5. Regulation of Obesity by the Alpha-arrestin ARRDC3
    Ronald B Myers; Fiscal Year: 2013
    ..The [unreadable]-arrestins are major regulators of cellular [unreadable]-adrenergic signaling...
  6. Functional Studies of the Incretin GIP Receptor in Adipocytes
    Timothy E McGraw; Fiscal Year: 2013
    ..In the AIM 3 we will characterize the roles of GPCR kinases (GRKs) and [unreadable]-arrestins in GIP signaling and GIPR traffic...
  7. Diabetic Cardiomyopathy and the Alpha Arrestin Proteins
    Richard T Lee; Fiscal Year: 2013
    ..The Beta Arrestins are well known as important regulators of receptor signaling, including beta adrenergic signaling...
  8. Regulation of Drosophila arrestins in light adaptation
    Bih Hwa Shieh; Fiscal Year: 2012
    ..Our insights into the in vivo regulation of arrestins in Drosophila will broaden our knowledge on the diverse functions that visual arrestins and [unreadable]-..
  9. Novel tools for identifying GPCR compounds modulating specific sub-cellular ERK a
    Haifeng Eishingdrelo; Fiscal Year: 2013
    ..We plan to utilize phosphorylated ERK2 interaction with receptor-associated ? -arrestins as signal readout for the assay development...
  10. Akt-regulated pathways in platelet function
    Donna S Woulfe; Fiscal Year: 2011
    ..Our preliminary studies show that arrestins form agonist-dependent complexes with p85-PI3K subunits in human platelets...
  11. REGULATION OF SIGNALING BY CELL-SURFACE PROTEOLYSIS
    Nigel W Bunnett; Fiscal Year: 2010
    ..proximity assays of protein-protein interactions, studies will examine the innovative concept that PARs and 2- arrestins assemble signaling complexes in endosomes that transmit sustained inflammatory signals...
  12. PAR-1 Signaling and HAND
    KATHLEEN ANNE MAGUIRE-ZEISS; Fiscal Year: 2013
    ..Recent studies have shown that select GPCRs can associate with ?-arrestins to activate the kinase glycogen synthase kinase-3??(GSK-3?) through a novel, non-canonical signaling pathway...
  13. SIGNALING PATHWAYS FOR UV-INDUCED MELANOGENIC RESPONSE
    Zalfa Abdel-Malek; Fiscal Year: 2012
    ..Third, we will define the roles of G protein receptor kinases (GRKs) and 2-arrestins in MC1R surface expression and sequestration...
  14. Regulation of Protease-activated Receptor-1 Signaling
    JoAnn Trejo; Fiscal Year: 2012
    ..Phosphorylation and arrestins are some important components that contribute to desensitization of PAR1 signaling, but other mechanisms are ..
  15. In Vivo Implications of Agonist Selective Activation of Delta Opioid Receptor
    Amynah Amir Ali Pradhan; Fiscal Year: 2012
    ..2-arrestins are major mediators of receptor internalization, and also mediate subsequent receptor signaling...
  16. Spatiotemporal regulation of beta adrenoceptor signaling in cardiacmyocytes
    Yang K Xiang; Fiscal Year: 2013
    ..We will examine the association of PDE4D isoforms with bAR subtype-activated arrestins and PKA in cardiac myocytes, the differential roles of arrestin 2 and 3 in controlling bAR subtype-induced cAMP/..
  17. Exploring a Role for beta-Arrestins in Cardiac Injury and Repair
    Anna M Gumpert; Fiscal Year: 2013
    ..Termination of GPCR signaling is followed by the recruitment of b-arrestins, which leads to physical uncoupling of the G protein from the receptor...
  18. Beta arrestin and NO signaling in endothelial cells
    Neetu Sud; Fiscal Year: 2010
    ..However the molecular mechanisms by which eNOS-HSP90 interactions are stimulated are not fully understood. Beta arrestins are ubiquitous multifunctional adaptor proteins of G-protein coupled receptors (GPCR)...
  19. In Vivo Implications of Agonist Selective Activation of Delta Opioid Receptor
    Amynah Amir Ali Pradhan; Fiscal Year: 2013
    ..unreadable]-arrestins are major mediators of receptor internalization, and also mediate subsequent receptor signaling...
  20. TYROSINE KINASES IN G PROTEIN MEDIATED SIGNALING
    Louis M Luttrell; Fiscal Year: 2013
    ..The central hypothesis of this proposal is that heterotrimeric G proteins and -arrestins serve as independent GPCR signal transducers that mediate distinct facets of the cellular response to GPCR ..
  21. GRK and b-Arrestin Signaling in Cardiac Regeneration
    Walter J Koch; Fiscal Year: 2013
    ..Interestingly, b-arrestins (b-arrestin1 and b-arrestin2 are in the heart) can also initiate intracellular signaling pathways after ..
  22. Signaling regulation in the striatum in Parkinson's disease
    Eugenia V Gurevich; Fiscal Year: 2013
    PROJECT SUMMARY G protein-coupled receptor kinases (GRK) and arrestins act in concert to ensure rapid termination of G protein- mediated signaling by G protein-coupled receptors...
  23. The role of receptor desensitization machinery in psychostimulant addiction
    Eugenia V Gurevich; Fiscal Year: 2012
    ..receptors, including dopamine receptors, is regulated by G protein-coupled receptor kinases (GRKs) and arrestins via the homologous desensitization mechanism...
  24. Signal Transduction of GPR56
    Lei Xu; Fiscal Year: 2013
    ..Mutagenesis analyses, radiolabeling assay, and expression analyses of shRNAs and mutant arrestins will be performed...
  25. Calcium sensing receptor and scaffolds
    GERDA BREITWIESER; Fiscal Year: 2009
    ..Preliminary data suggests CaR interactions with arrestins-1 and -2 modulate intracellular calcium responses and MARK signaling...
  26. Circadian Photoentrainment in Mammals
    Satchidananda Panda; Fiscal Year: 2013
    ..Next, we will assess melanopsin function in mice lacking individual beta-arrestins. Mice with perturbations in melanopsin phosphorylation, kinase activity or arrestin expression will be subject ..
  27. G-PROTEIN-DEPENDENT AND -INDEPENDENT KINASE SIGNALING IN CARDIAC HYPERTROPHY
    Gerald W Dorn; Fiscal Year: 2013
    ..G- protein/PKC signaling, but concomitantly activate alternate G-protein-independent signaling through b- arrestins. For these reasons, we have developed novel floxed GRK and PKC isoform mice and used them to create unique ..
  28. Engagement of heterotrimeric G proteins by Sonic hedgehog
    DAVID RANDELL MANNING; Fiscal Year: 2010
    ..targets, mimic the actions of targets in pertussis toxin-treated cells, and evaluate recruitment through Gi of 2-arrestins. The third aim is to evaluate the requirement for Gi among primary cells serving as targets for Shh, ..
  29. Beta2 Adrenoceptor Structure and Mechanism of Activation
    Brian K Kobilka; Fiscal Year: 2013
    ..GPCR can activate more than one G protein subtype as well as G protein independent signaling pathways such as arrestins. Many GPCRs exhibit basal, agonist independent activity...
  30. The Role of Protein Kinase C in Opioid Tolerance
    William L Dewey; Fiscal Year: 2010
    ..goal of the research is to elucidate the relative importance of PKC to other cellular proteins such as PKA, arrestins, GRK etc in opioid tolerance...
  31. Arrestin Selectivity for GPCRs in Airway Smooth Muscle
    Julia K L Walker; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Arrestins regulate numerous G protein-coupled receptors (GPCRs) by disrupting GPCR-G protein interaction and "arresting" the ability of receptors to signal...
  32. Arrestins in TLR4 Signaling in Macrophages
    Narayanan Parameswaran; Fiscal Year: 2013
    ..Recent studies have demonstrated a critical role for non-visual arrestins (ARR2 and ARR3) in the regulation of TLR signaling and pathophysiology...
  33. Agonist-Directed MOR Desensitization in Opioid Analgesic Tolerance
    Laura M Bohn; Fiscal Year: 2010
    ..b>arrestins are involved in desensitizing and regulating opioid receptors and the removal ?arrestin2 in mice increases ..
  34. TRPV1 regulation by B-arrestins
    ELAINE DARCEY POR; Fiscal Year: 2012
    ..Interestingly, Beta-arrestins a family of cytosolic proteins initially identified for their central role in G-protein coupled receptor (GPCR) ..
  35. Crystallization and structure determination of the angiotensin II type 1 receptor
    Brian K Kobilka; Fiscal Year: 2012
    ..stabilizes an active conformation of the receptor capable of signaling through both the G proteins and the ? -arrestins, and (3) a highly specific ? -arrestin biased agonist that stabilizes a conformation of the receptor that is ..
  36. Mechanisms Regulating GPCR Trafficking
    JoAnn Trejo; Fiscal Year: 2013
    ..Internalization of activated GPCRs occurs through a clathrin- and dynamin-dependent pathway that requires arrestins. However, arrestins are not essential for internalization of all GPCRs...
  37. Mechanisms of the anti-dyskinetic effects of GRK3 in the parkinsonian striatum
    YONATAN CARL; Fiscal Year: 2012
    ..This system of self-regulation relies upon two key proteins, the GPCR kinases, or GRKs, and the arrestins, to adequately control dopamine signal...
  38. Role of Arrestins in G Protein-Coupled Receptor Regulation
    Jeffrey L Benovic; Fiscal Year: 2013
    ..Two protein families, GPCR kinases (GRKs) and arrestins, play a critical role in these processes...
  39. Novel Mechanisms and Therapies in Heart Failure
    Howard A Rockman; Fiscal Year: 2013
    ..to explore the interplay of two universal mechanisms for signaling by betaARs, activation of G proteins and beta-arrestins, and how these are regulated by post-translational modifications (phosphorylation, ubiquitination, S-..
  40. Structure-function studies of visual arrestin
    Vsevolod V Gurevich; Fiscal Year: 2013
    PROJECT SUMMARY Visual arrestins are key players in photoreceptor signaling, governing the rate of signal shutoff and photoresponse recovery...
  41. Structure and function of dopamine receptors.
    Jonathan A Javitch; Fiscal Year: 2013
    ..being to determine the molecular composition of the receptor signaling unit that interacts with G proteins or arrestins, thus clarifying the role of oligomerization in GPCR functio and the potential for exploiting receptor ..
  42. MLP Assay for Arrestin-AP2 Inhibitors
    Eric R Prossnitz; Fiscal Year: 2012
    ..Arrestin mediates internalization via a domain that binds directly to clathrin and the adapter AP-2. Arrestins also bind to kinases and other signaling proteins...
  43. Drug abuse: Discovering ligands for pertinent GPCRs
    Marc G Caron; Fiscal Year: 2013
    ..and maintenance of receptor cDNA and cell assay libraries, particularly containing fluorescent beta-arrestins and NIDA GPCR targets, for immediately access by NIDA investigators...
  44. NEUROGENIC MECHANISMS OF INTESTINAL INFLAMMATION
    Eileen Grady; Fiscal Year: 2006
    ..of SP by the cell surface-enzyme neutral endopeptidase (NEP) and desensitization of the NK 1 R by Beta-arrestins, were found to terminate signaling by SP...
  45. Arrestin interactions with non-receptor binding partners
    Vsevolod V Gurevich; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Arrestins were first described as negative regulators of G protein-coupled receptor (GPCR) signaling via G proteins...
  46. Activation and regulation of the neural stem cell-expressed receptor GPR56
    Randy A Hall; Fiscal Year: 2013
    ..by cytoplasmic binding partners of the receptor that have been identified in preliminary work, including beta-arrestins and PDZ scaffolds...
  47. RESPONSIVENESS OF GNRH RECEPTOR SIGNALING
    JIMMY NEILL; Fiscal Year: 2002
    ..of GnRH receptor signaling are members of the GRK family (G protein coupled receptor kinases) and beta arrestins 1 and 2...
  48. Parathyroid Hormone and Osteoblast Mitogenesis
    Louis Luttrell; Fiscal Year: 2005
    ..Second, beta-arrestins, proteins which bind to agonist-occupied GPCRs and uncouple them from their cognate G proteins, function as ..
  49. REGULATORY DOMAINS OF G PROTEIN COUPLED RECEPTORS
    Ellen Weiss; Fiscal Year: 2002
    ..between G protein-coupled receptors and their G proteins, as well as the G protein-coupled receptor kinases and arrestins that mediate receptor desensitization...
  50. ANTIPSYCHOTICS AND RECEPTOR DESENSITIZATION MACHINERY
    Eugenia Gurevich; Fiscal Year: 2002
    DESCRIPTION: (Adapted from applicant's abstract) Arrestins and G protein-coupled receptor kinases (GRKs) participate in homologous desensitization of hundreds of G protein-coupled receptors (GPCRs)...
  51. RECEPTORS FOR CCK AND OTHER GI-HORMONES
    Craig Logsdon; Fiscal Year: 2004
    ..important in receptor trafficking will be explored, including G protein-coupled receptor kinases (GRKs) and arrestins, in pancreatic acinar cells from humans and mice...
  52. Melatonin Regulation of MT2 Melatonin Receptors
    MATTHEW GERDIN; Fiscal Year: 2003
    ..Using dominant negatives of G protein receptor kinases (GRK), arrestins, and dynamin, confocal microscopic and cell surface biotinylation experiments will examine the process of CHO-..
  53. Arestin Interaction with Endocytic Components
    JEFFREY BENOVIC; Fiscal Year: 2006
    b>Arrestins play an essential role in regulating signaling and trafficking of G protein-coupled receptors (GPCRs)...
  54. Mouse model for juvenile granulosa cell tumorogenesis
    ROSEMARY STEINEMETZ; Fiscal Year: 2004
    ..other essential components of this pathway, such as the G protein-coupled receptor kinases (GRKs) and the arrestins have never been examined for abnormalities that might lead to hyperstimulation...
  55. Role of beta-arrestin-dependent chemotaxis in protease-activated-receptor-2-induc
    Kathryn DeFea; Fiscal Year: 2009
    ..demonstrated multiple G-protein-independent effects of PAR-2, that are mediated by a family of proteins called 2-arrestins (6;9;10;13;17;18)...
  56. MOLECULAR REGULATION OF D1 DOPAMINE RECEPTOR FUNCTION
    Richard Mailman; Fiscal Year: 2004
    ..The complement of Q-arrestins will be determined, and alterations in high affinity binding of GRKs and arrestins to D1 receptors measured ..
  57. Role of Arrestin in Olfactory Desensitization
    CATHERINE MERRILL; Fiscal Year: 2003
    ..gambiae, an arrestin gene, AgArr1. As arrestins are known to desensitize heptahelical receptors (such as odorant receptors), these studies will initially ..
  58. MOLECULAR GENETICS OF OLFACTION IN ANOPHELINE MOSQUITOES
    LAURENCE ZWIEBEL; Fiscal Year: 2004
    ..that these genes encoding odorant binding proteins (OBPs), odorant receptors (ORs) and their corresponding arrestins are more likely to be specific for host seeking behaviors in this vector rather than downstream, and therefore ..
  59. ARRESTINS IN G PROTEIN-COUPLE RECEPTOR REGULATION
    JEFFREY BENOVIC; Fiscal Year: 2005
    ..Two protein families, G protein-coupled receptor kinases (GRKs) and arrestins, play a critical role in regulating these processes...
  60. Regulation of Cardiac Adrenergic Function by S-nitrosylation
    JONATHAN STAMLER; Fiscal Year: 2009
    ..In particular, we have recently identified the ?-arrestins (?arr1 and ?arr2) as targets of ?-AR-coupled S- nitrosylation by NO synthases (eNOS and nNOS)...
  61. Opioid Regulation in a Single Neuron
    Seksiri Arttamangkul; Fiscal Year: 2007
    ..becomes a good substrate for phosphorylation by G protein-coupled receptor kinase (GRK), the recruitment of beta-arrestins and subsequent association with clathrin-coated pits...
  62. The Function of Arrestin in Drosophila Behavior
    Gregg Roman; Fiscal Year: 2005
    ..A primary function of arrestins, to down regulate activated GPCRs, suggests that these proteins are fundamental to the processes of sensory ..
  63. STUDIES ON B2-ADRENERGIC RECEPTOR MRNA BINDING PROTEIN
    BABY THOLANIKUNNEL; Fiscal Year: 2004
    ..post-translational protein modification such as phosphorylation, interactions with regulatory proteins such as arrestins and receptors kinases, and physical sequestration of the receptor away from other signaling components Despite ..
  64. Arrestins in G protein-coupled receptor trafficking
    GREGORY FRALISH; Fiscal Year: 2005
    G protein-coupled receptors (GPCRs) mediate many important physiological responses. Arrestins regulate desensitization and endocytosis of agonist-occupied GPCRs by acting as protein scaffolds for clathrin and the AP2 adaptor complex...
  65. Biophysical Analysis of Opioid Receptor Structure
    Brian Kobilka; Fiscal Year: 2005
    ..functionally distinct receptor conformational states that differ in their interactions with G proteins, kinases, arrestins and possibly other signaling molecules...
  66. REGULATION OF M2 MUSCARINIC RECEPTORS
    Linda Hicke; Fiscal Year: 2001
    ..In other systems, arrestins bind to phosphorylated GPRs to cause R/G uncoupling and guide GPRs to clathrin coated pits for endocytosis...