Robert Lefkowitz

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. ncbi request reprint Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins
    Stephen J Perry
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 298:834-6. 2002
  2. ncbi request reprint Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination
    Sudha K Shenoy
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:14498-506. 2003
  3. ncbi request reprint beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation
    William G Barnes
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:8041-50. 2005
  4. ncbi request reprint Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:15315-24. 2005
  5. ncbi request reprint Seven-transmembrane receptor signaling through beta-arrestin
    Sudha K Shenoy
    Howard Hughes Medical Institute, Durham, NC 27710, USA
    Sci STKE 2005:cm10. 2005
  6. ncbi request reprint The superfamily of heptahelical receptors
    R J Lefkowitz
    Howard Hughes Medical Institute and Departments of Medicine Cardiology and Biochemistry, Duke University Medical Centre, Durham, North Carolina 27710, USA
    Nat Cell Biol 2:E133-6. 2000
  7. ncbi request reprint Transduction of receptor signals by beta-arrestins
    Robert J Lefkowitz
    Howard Hughes Medical Institute, Durham, NC 27710, USA
    Science 308:512-7. 2005
  8. ncbi request reprint Summary of Wenner-Gren international symposium receptor-receptor interactions among heptaspanning membrane receptors: from structure to function
    Robert J Lefkowitz
    Howard Hughes Medical Institute Professor of Medicine and Biochemistry, Duke University Medical Center, Durham, NC, USA
    J Mol Neurosci 26:293-4. 2005
  9. ncbi request reprint Historical review: a brief history and personal retrospective of seven-transmembrane receptors
    Robert J Lefkowitz
    Howard Hughes Medical Institute, James B Duke Professor of Medicine, Duke University Medical Center, Room 468, CARL Bldg, Research Drive, DUMC Box 3821, Durham, NC 27710, USA
    Trends Pharmacol Sci 25:413-22. 2004
  10. ncbi request reprint Seven transmembrane receptors: a brief personal retrospective
    Robert J Lefkowitz
    Howard Hughes Medical Institute at Duke University Medical Center, Department of Medicine, Durham, NC 27710, USA
    Biochim Biophys Acta 1768:748-55. 2007

Detail Information

Publications72

  1. ncbi request reprint Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins
    Stephen J Perry
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 298:834-6. 2002
    ....
  2. ncbi request reprint Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination
    Sudha K Shenoy
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:14498-506. 2003
    ..Thus the ubiquitination status of beta-arrestin determines the stability of the receptor-beta-arrestin complex as well as the trafficking pattern of beta-arrestin...
  3. ncbi request reprint beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation
    William G Barnes
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:8041-50. 2005
    ....
  4. ncbi request reprint Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:15315-24. 2005
    ....
  5. ncbi request reprint Seven-transmembrane receptor signaling through beta-arrestin
    Sudha K Shenoy
    Howard Hughes Medical Institute, Durham, NC 27710, USA
    Sci STKE 2005:cm10. 2005
    ..Beta-arrestins act as endocytic adaptors and signal mediators not only for the 7TMRs, but also for several receptor tyrosine kinases...
  6. ncbi request reprint The superfamily of heptahelical receptors
    R J Lefkowitz
    Howard Hughes Medical Institute and Departments of Medicine Cardiology and Biochemistry, Duke University Medical Centre, Durham, North Carolina 27710, USA
    Nat Cell Biol 2:E133-6. 2000
    ..Here I provide a personal perspective on events leading up to and flowing from this exciting discovery that opened up a vast field of research...
  7. ncbi request reprint Transduction of receptor signals by beta-arrestins
    Robert J Lefkowitz
    Howard Hughes Medical Institute, Durham, NC 27710, USA
    Science 308:512-7. 2005
    ..This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular functions through a rapidly expanding list of signaling pathways...
  8. ncbi request reprint Summary of Wenner-Gren international symposium receptor-receptor interactions among heptaspanning membrane receptors: from structure to function
    Robert J Lefkowitz
    Howard Hughes Medical Institute Professor of Medicine and Biochemistry, Duke University Medical Center, Durham, NC, USA
    J Mol Neurosci 26:293-4. 2005
    ..Another potentially interesting function of some orphan receptors might be to act as chaperones for other receptors, helping to bring them to the cell surface and stabilizing their membrane expression...
  9. ncbi request reprint Historical review: a brief history and personal retrospective of seven-transmembrane receptors
    Robert J Lefkowitz
    Howard Hughes Medical Institute, James B Duke Professor of Medicine, Duke University Medical Center, Room 468, CARL Bldg, Research Drive, DUMC Box 3821, Durham, NC 27710, USA
    Trends Pharmacol Sci 25:413-22. 2004
    ..Numerous opportunities for novel therapeutics should emerge from current and future research on 7TM receptor biology...
  10. ncbi request reprint Seven transmembrane receptors: a brief personal retrospective
    Robert J Lefkowitz
    Howard Hughes Medical Institute at Duke University Medical Center, Department of Medicine, Durham, NC 27710, USA
    Biochim Biophys Acta 1768:748-55. 2007
    ..Here I set down some personal reflections on the evolution of the field during the past 35 years, hanging the thread of the story on some of the work from my own laboratory...
  11. ncbi request reprint 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
    ..The beta-arrestins are also found to be involved in the regulation of novel receptor systems, such as Frizzled and TGFbeta receptors...
  12. pmc The annual ASCI meeting: does nostalgia have a future?
    Robert J Lefkowitz
    Howard Hughes Medical Institute, Department of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Clin Invest 118:1231-3. 2008
    ..In this brief essay, I set down some miscellaneous recollections of these meetings and some thoughts about why they were of such central importance in the careers of those of my generation...
  13. ncbi request reprint Dancing with different partners: protein kinase a phosphorylation of seven membrane-spanning receptors regulates their G protein-coupling specificity
    Robert J Lefkowitz
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Pharmacol 62:971-4. 2002
  14. ncbi request reprint Seven transmembrane receptors: something old, something new
    R J Lefkowitz
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Acta Physiol (Oxf) 190:9-19. 2007
    ....
  15. ncbi request reprint 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
    ..These findings demonstrate that the beta2AR can signal to ERK via a GRK5/6-beta-arrestin-dependent pathway, which is independent of G protein coupling...
  16. ncbi request reprint The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation
    Akira Tohgo
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:6258-67. 2003
    ....
  17. ncbi request reprint Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation
    Diane Gesty-Palmer
    Department of Medicine, Howard Hughes Medical Institute, Duke University, Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:10856-64. 2006
    ..These findings imply the existence of distinct active conformations of the hPTH1R responsible for the two pathways, which can be stimulated by unique ligands. Such ligands may have distinct and valuable therapeutic properties...
  18. ncbi request reprint G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95
    Liaoyuan A Hu
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:1607-13. 2002
    ..Regulation of protein association through receptor phosphorylation may be a general mechanism used by G protein-coupled receptors that associate via PDZ domain-mediated protein/protein interactions...
  19. ncbi request reprint Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestins
    Christopher D Nelson
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Science 315:663-6. 2007
    ..Thus, beta-arrestins can serve similar regulatory functions for disparate classes of 7TMRs through structurally dissimilar enzymes that degrade chemically distinct second messengers...
  20. pmc Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptor
    Christopher D Nelson
    Howard Hughes Medical Institute, Departments of Medicine, Immunology, and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 283:21093-101. 2008
    ..Collectively, these data support a model in which beta-arrestins direct the localization of PIP5K Ialpha and PIP(2) production to agonist-activated 7TMRs, thereby regulating receptor internalization...
  21. ncbi request reprint Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling
    Wei Chen
    Howard Hughes Medical Institute, Duke University Medical Center, Departments of Medicine and Biochemistry, Durham, NC 27710, USA
    Science 301:1394-7. 2003
    ..Thus, the regulatory actions of beta-arrestins are broader than previously appreciated, extending to the TGF-beta receptor family as well...
  22. pmc Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptors
    Arun K Shukla
    Department of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 105:9988-93. 2008
    ..Our data thus highlight another interesting aspect of 7TMR signaling--i.e., functionally specific receptor conformations can be translated to downstream effectors such as beta-arrestins, thereby governing their functional specificity...
  23. ncbi request reprint beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation
    Akira Tohgo
    Howard Hughes Medical Institute and the Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:9429-36. 2002
    ..These data demonstrate that beta-arrestins facilitate GPCR-mediated ERK activation but inhibit ERK-dependent transcription by binding to phospho-ERK1/2, leading to its retention in the cytosol...
  24. ncbi request reprint 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
    ....
  25. ncbi request reprint GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation
    Liaoyuan A Hu
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:26295-301. 2003
    ..These data suggest that GIPC can regulate beta1-adrenergic receptor-stimulated, Gi-mediated, ERK activation while having no effect on receptor internalization or Gs-mediated cAMP signaling...
  26. 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
    ..GRK2 suppression actually increased beta-arrestin-stimulated ERK activation. These results suggest that beta-arrestin recruited in response to receptor phosphorylation by different GRKs has distinct functional potentials...
  27. ncbi request reprint Stable interaction between beta-arrestin 2 and angiotensin type 1A receptor is required for beta-arrestin 2-mediated activation of extracellular signal-regulated kinases 1 and 2
    Huijun Wei
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:48255-61. 2004
    ..These findings demonstrate how the ability of receptors to interact with beta-arrestins determines both the mechanism of ERK activation as well as the physiological consequences of this activation...
  28. ncbi request reprint Activation-dependent conformational changes in {beta}-arrestin 2
    Kunhong Xiao
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 279:55744-53. 2004
    ....
  29. ncbi request reprint 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
    ..Thus, these studies demonstrate the potential for developing a novel class of 7TMR ligands with a distinct bias for beta-arrestin-mediated signaling...
  30. ncbi request reprint 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...
  31. pmc S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor trafficking
    Kentaro Ozawa
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 31:395-405. 2008
    ..Thus, beta-arrestin subserves the functional coupling of eNOS and GPCRs, and dynamic S-nitrosylation/denitrosylation of beta-arrestin 2 regulates stimulus-induced GPCR trafficking...
  32. ncbi request reprint G-protein-coupled receptor (GPCR) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCR
    William E Miller
    Departments of Medicine and Biochemistry, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 278:21663-71. 2003
    ..Understanding the regulation of viral GPCRs by GRKs and beta-arrestins will provide important new insights into not only aspects of viral pathogenesis but also basic mechanisms of receptor signaling...
  33. pmc Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference
    Seungkirl Ahn
    The Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 100:1740-4. 2003
    ..This approach should allow discovery of novel signaling and regulatory roles for the beta-arrestins in many seven-membrane-spanning receptor systems...
  34. 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
    ..Furthermore, G protein-biased ligands that activate GPR109A in a beta-arrestin-independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia...
  35. ncbi request reprint Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors
    Fang Tsyr Lin
    Howard Hughes Medical Institute and Departments of Medicine and Biochemistry, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Biochemistry 41:10692-9. 2002
    ..Thus it appears that the function of all arrestin family members in mediating internalization of G protein-coupled receptors is regulated by distinct phosphorylation/dephosphorylation mechanisms...
  36. ncbi request reprint 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
    ..These newly appreciated attributes of these two families of protein highlight their unique ability to coordinate the various aspects of 7TMR functions...
  37. ncbi request reprint Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted system
    A Musa Zamah
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 277:31249-56. 2002
    ..These results provide strong experimental support for the idea that PKA-mediated phosphorylation of the beta(2)-adrenergic receptor switches its predominant coupling from G(s) to G(i)...
  38. ncbi request reprint 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
    Kelly N Nobles
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 282:21370-81. 2007
    ..This study represents the first direct evidence that the "receptor-bound" conformations of beta-arrestins1 and 2 are different...
  39. pmc Beta-arrestin-mediated signaling regulates protein synthesis
    Scott M DeWire
    Department of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:10611-20. 2008
    ..This novel demonstration that beta-arrestins regulate protein synthesis reveals that the spectrum of beta-arrestin-mediated signaling events is broader than previously imagined...
  40. pmc Beta-arrestin-mediated localization of smoothened to the primary cilium
    Jeffrey J Kovacs
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Science 320:1777-81. 2008
    ..These results suggest roles for beta-arrestins in mediating the intracellular transport of a 7TMR to its obligate subcellular location for signaling...
  41. ncbi request reprint Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2
    Seungkirl Ahn
    Howard Hughes Medical Institute, Department of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:7807-11. 2004
    ....
  42. ncbi request reprint Regulation of V2 vasopressin receptor degradation by agonist-promoted ubiquitination
    Negin P Martin
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:45954-9. 2003
    ..However, receptor stimulation leads to rapid beta-arrestin2-dependent ubiquitination of the receptor and increased degradation...
  43. ncbi request reprint Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor
    Seungkirl Ahn
    Howard Hughes Medical Institute, Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:26642-51. 2002
    ..Thus, c-Src-mediated tyrosine phosphorylation is required for the function of dynamin in ligand-induced signaling receptor internalization...
  44. ncbi request reprint Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxis
    Dacia L Hunton
    Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Box 3821, Duke University Medical Center, Durham, NC 27710, USA
    Mol Pharmacol 67:1229-36. 2005
    ..These data suggest that beta-arrestin 2 can mediate chemotaxis through mechanisms which may be G-protein-independent (Ang II receptors) or -dependent (LPA receptors)...
  45. pmc Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 106:6650-5. 2009
    ..Thus, USP33-beta-arrestin interaction is a key regulatory step in 7TMR trafficking and signal transmission from the activated receptors to downstream effectors...
  46. 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
    ....
  47. ncbi request reprint 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
    ..Here, we review the signaling capacities of these versatile adapter molecules and discuss the possible implications for cellular processes such as chemotaxis and apoptosis...
  48. pmc 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
    Jihee Kim
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 284:11953-62. 2009
    ....
  49. 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
    ..These findings establish a key role for beta-arrestin-2 in mediating cellular cytoprotective functions by a 7-transmembrane receptor and define the biochemical pathways involved...
  50. pmc Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration
    Jihee Kim
    Department of Medicine Cardiology, Duke University Medical Center, Durham, NC 27710, USA
    Circ Res 103:70-9. 2008
    ..These findings identify inhibition of beta-arrestin2 as a novel therapeutic strategy for combating atherosclerosis and arterial restenosis after angioplasty...
  51. pmc Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor
    Larry S Barak
    Box 3287, Duke University, Durham, NC 27710
    Mol Pharmacol 74:585-94. 2008
    ....
  52. pmc Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation
    Sudha K Shenoy
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 282:29549-62. 2007
    ....
  53. ncbi request reprint 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
    ....
  54. ncbi request reprint Seven-transmembrane-spanning receptors and heart function
    Howard A Rockman
    Departments of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 415:206-12. 2002
    ..Most of these discoveries have focused on the most common type of cardiac receptor - the seven-transmembrane-spanning receptor or G-protein-coupled receptor...
  55. 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
    ....
  56. ncbi request reprint Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis
    Thomas J Povsic
    Division of Cardiology, Department of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:51334-9. 2003
    ....
  57. 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
    ..These data uncover a role of beta-arrestins in the regulation of NF-kappaB-mediated gene regulation...
  58. ncbi request reprint PKA-mediated phosphorylation of the beta1-adrenergic receptor promotes Gs/Gi switching
    Negin P Martin
    Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Cell Signal 16:1397-403. 2004
    ..These results strongly support the hypothesis that the beta(1)-AR, like the beta(2)-AR, can undergo PKA-dependent "G(s)/G(i) switching"...
  59. ncbi request reprint 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...
  60. ncbi request reprint Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways
    Antonio Rapacciuolo
    Department of Medicine and Cell Biology, Medical Center, Duke University, Durham, North Carolina 27710, USA
    J Biol Chem 278:35403-11. 2003
    ..e. PKA-mediated phosphorylation directs internalization via a caveolae pathway, whereas GRK-mediated phosphorylation directs it through clathrin-coated pits...
  61. 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
    ..These findings indicate distinct functional capabilities of beta-arrestins bound to receptors phosphorylated by different classes of GRKs...
  62. ncbi request reprint G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor elucidated by diacylglycerol dynamics
    Jonathan D Violin
    Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:36411-9. 2006
    ....
  63. ncbi request reprint G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by fluorescence resonance energy transfer
    Jonathan D Violin
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:20577-88. 2006
    ..Because GRK isoforms vary in their regulation, this partially redundant system ensures beta-arrestin recruitment while providing the opportunity for tissue-specific regulation of the rate of beta-arrestin recruitment...
  64. ncbi request reprint 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
    ..Furthermore, the utility of a pharmacological strategy aimed at targeting this GPCR desensitization machinery to regulate brain functions can be envisaged...
  65. ncbi request reprint Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors
    Qin Wang
    Department of Pharmacology and Center of Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Science 304:1940-4. 2004
    ..The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses...
  66. ncbi request reprint {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...
  67. ncbi request reprint Homo- and hetero-oligomerization of thyrotropin-releasing hormone (TRH) receptor subtypes. Differential regulation of beta-arrestins 1 and 2
    Aylin C Hanyaloglu
    7TM Receptor Laboratory, Western Australian Institute for Medical Research WAIMR, University of Western Australia, Centre for Medical Research, Nedlands, Perth, WA 6009, Australia
    J Biol Chem 277:50422-30. 2002
    ..This study demonstrates that TRHR subtypes are differentially regulated by the beta-arrestins and also provides the first evidence that the interactions of TRHRs with beta-arrestin may be altered by hetero-oligomer formation...
  68. ncbi request reprint Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma
    David T Lodowski
    Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
    Science 300:1256-62. 2003
    ....
  69. 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
    ..Thus, receptor-stimulated beta-arrestin-mediated recruitment of PDE4 plays a central role in the regulation of G protein switching by the beta(2)AR in a physiological system, the cardiac myocyte...
  70. ncbi request reprint Constitutive protease-activated receptor-2-mediated migration of MDA MB-231 breast cancer cells requires both beta-arrestin-1 and -2
    Lan Ge
    Division of Biomedical Sciences, Biochemical and Molecular Biology Program and Cellular, Molecular and Developmental Biology Program, University of California, Riverside, CA 92521, USA
    J Biol Chem 279:55419-24. 2004
    ....
  71. ncbi request reprint beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation
    May M Paing
    Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599 7365, USA
    J Biol Chem 277:1292-300. 2002
    ....
  72. ncbi request reprint Beta-arrestin and Mdm2 mediate IGF-1 receptor-stimulated ERK activation and cell cycle progression
    Leonard Girnita
    Department of Oncology and Pathology, Division of Cellular and Molecular Tumor Pathology, CCK, R8 04, Karolinska Hospital, SE 171 76 Stockholm, Sweden, and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Biol Chem 282:11329-38. 2007
    ..These data suggest that beta-arrestin-dependent ERK signaling by the IGF-1R regulates cell cycle progression and may thus be an important regulator of the growth of normal and malignant cells...

Research Grants32

  1. MOLECULAR REGULATION OF CARDIAC ADRENERGIC RECEPTORS
    Robert Lefkowitz; Fiscal Year: 1999
    ..Moreover, the results have the potential to point the way toward novel therapeutic strategies for cardiovascular diseases. ..
  2. Molecular Regulation of Cardiovascular 7 TM Receptors
    Robert J Lefkowitz; Fiscal Year: 2010
    ....
  3. MOLECULAR REGULATION OF CARDIAC ADRENERGIC RECEPTORS
    Robert Lefkowitz; Fiscal Year: 2004
    ..Understanding of the regulation of beta-ARs may point toward novel therapeutic strategies for cardiovascular diseases. ..
  4. B-Arrestins and GPCR Kinases in Vascular Function/Growth
    Robert Lefkowitz; Fiscal Year: 2005
    ..These experiments have the potential to lead to the development of new strategies for limiting vein graft failure and restenosis. ..
  5. Molecular Regulation of Cardiovascular 7 TM Receptors
    Robert Lefkowitz; Fiscal Year: 2007
    ..The resulting understanding of the molecular basis of the newly appreciated GRK and a-arrestin-mediated signaling pathways should point the way toward development of novel therapeutics for cardiovascular diseases. ..
  6. B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular Function
    Robert Lefkowitz; Fiscal Year: 2009
    ....
  7. Molecular Regulation of Cardiovascular 7 TM Receptors
    Robert Lefkowitz; Fiscal Year: 2009
    ..The resulting understanding of the molecular basis of the newly appreciated GRK and a-arrestin-mediated signaling pathways should point the way toward development of novel therapeutics for cardiovascular diseases. ..
  8. B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular Function
    Robert Lefkowitz; Fiscal Year: 2009
    ..These experiments have the potential to delineate an entirely novel and general mode of receptor-mediated signaling and to point the way to the development of novel therapeutics which target this recently discovered signaling mechanism. ..
  9. B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular Function
    Robert J Lefkowitz; Fiscal Year: 2010
    ....
  10. MOLECULAR PROPERTIES OF CARDIAC ADRENERGIC RECEPTORS
    Robert Lefkowitz; Fiscal Year: 1980
    ....