Research Topics
Genomes and Genes | Robert LefkowitzSummaryAffiliation: Duke University Medical Center Country: USA Publications
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Publications
Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestinsStephen J Perry
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Science 298:834-6. 2002....- Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitinationSudha 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... - beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulationWilliam G Barnes
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 280:8041-50. 2005.... - Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomesSudha K Shenoy
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 280:15315-24. 2005.... - Seven-transmembrane receptor signaling through beta-arrestinSudha 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... - The superfamily of heptahelical receptorsR 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... - Transduction of receptor signals by beta-arrestinsRobert 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... - Summary of Wenner-Gren international symposium receptor-receptor interactions among heptaspanning membrane receptors: from structure to functionRobert 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... - Historical review: a brief history and personal retrospective of seven-transmembrane receptorsRobert 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... - Seven transmembrane receptors: a brief personal retrospectiveRobert 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... - beta-arrestins: traffic cops of cell signalingRobert 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... 
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...- Dancing with different partners: protein kinase a phosphorylation of seven membrane-spanning receptors regulates their G protein-coupling specificityRobert J Lefkowitz
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
Mol Pharmacol 62:971-4. 2002 - Seven transmembrane receptors: something old, something newR J Lefkowitz
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
Acta Physiol (Oxf) 190:9-19. 2007.... - beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptorSudha 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... - The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activationAkira Tohgo
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 278:6258-67. 2003.... - Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activationDiane 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... - G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95Liaoyuan 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... - Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestinsChristopher 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... - Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptorChristopher 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... - Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signalingWei 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... - Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptorsArun 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... - beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulationAkira 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... - An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behaviorJean 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.... - GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activationLiaoyuan 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... - Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptorXiu-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... - 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 2Huijun 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... - Activation-dependent conformational changes in {beta}-arrestin 2Kunhong Xiao
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
J Biol Chem 279:55744-53. 2004.... - beta-arrestin-biased agonism at the beta2-adrenergic receptorMatthew 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... - Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4Wei 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... - S-nitrosylation of beta-arrestin regulates beta-adrenergic receptor traffickingKentaro 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... - G-protein-coupled receptor (GPCR) kinase phosphorylation and beta-arrestin recruitment regulate the constitutive signaling activity of the human cytomegalovirus US28 GPCRWilliam 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... - Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interferenceSeungkirl 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... - beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in miceRobert 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... - Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptorsFang 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... - GRKs and beta-arrestins: roles in receptor silencing, trafficking and signalingEric 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... - Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted systemA 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)... - 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 -2Kelly 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... - Beta-arrestin-mediated signaling regulates protein synthesisScott 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... - Beta-arrestin-mediated localization of smoothened to the primary ciliumJeffrey 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... - Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2Seungkirl 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.... - Regulation of V2 vasopressin receptor degradation by agonist-promoted ubiquitinationNegin 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... - Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptorSeungkirl 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... - Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated pathway of chemotaxisDacia 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)... - Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2Sudha 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... - Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7Sudarshan Rajagopal
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Proc Natl Acad Sci U S A 107:628-32. 2010.... - Beta-arrestins and cell signalingScott 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... - 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 receptorJihee Kim
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
J Biol Chem 284:11953-62. 2009.... - {beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD PhosphorylationSeungkirl 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... - Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migrationJihee 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... 
Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensorLarry S Barak
Box 3287, Duke University, Durham, NC 27710
Mol Pharmacol 74:585-94. 2008....- Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activationSudha K Shenoy
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 282:29549-62. 2007.... - New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptorsRobert J Lefkowitz
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
Mol Cell 24:643-52. 2006.... - Seven-transmembrane-spanning receptors and heart functionHoward 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... - Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2Huijun 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.... - Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosisThomas 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.... - beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalphaD 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... - PKA-mediated phosphorylation of the beta1-adrenergic receptor promotes Gs/Gi switchingNegin 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"... - Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2Wei 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... - Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathwaysAntonio 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... - Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signalingJihee 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... - G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor elucidated by diacylglycerol dynamicsJonathan 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.... - G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by fluorescence resonance energy transferJonathan 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... - Desensitization of G protein-coupled receptors and neuronal functionsRaul 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... - Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptorsQin 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... - {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 ligaseLeonard 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... - Homo- and hetero-oligomerization of thyrotropin-releasing hormone (TRH) receptor subtypes. Differential regulation of beta-arrestins 1 and 2Aylin 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... - Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and GbetagammaDavid 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.... - beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to GiGeorge 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... - Constitutive protease-activated receptor-2-mediated migration of MDA MB-231 breast cancer cells requires both beta-arrestin-1 and -2Lan 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.... - beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulationMay 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.... - Beta-arrestin and Mdm2 mediate IGF-1 receptor-stimulated ERK activation and cell cycle progressionLeonard 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 Grants
- MOLECULAR REGULATION OF CARDIAC ADRENERGIC RECEPTORSRobert Lefkowitz; Fiscal Year: 1999..Moreover, the results have the potential to point the way toward novel therapeutic strategies for cardiovascular diseases. ..
- Molecular Regulation of Cardiovascular 7 TM ReceptorsRobert J Lefkowitz; Fiscal Year: 2010....
- MOLECULAR REGULATION OF CARDIAC ADRENERGIC RECEPTORSRobert Lefkowitz; Fiscal Year: 2004..Understanding of the regulation of beta-ARs may point toward novel therapeutic strategies for cardiovascular diseases. ..
- B-Arrestins and GPCR Kinases in Vascular Function/GrowthRobert Lefkowitz; Fiscal Year: 2005..These experiments have the potential to lead to the development of new strategies for limiting vein graft failure and restenosis. ..
- Molecular Regulation of Cardiovascular 7 TM ReceptorsRobert 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. ..
- B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular FunctionRobert Lefkowitz; Fiscal Year: 2009....
- Molecular Regulation of Cardiovascular 7 TM ReceptorsRobert 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. ..
- B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular FunctionRobert 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. ..
- B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular FunctionRobert J Lefkowitz; Fiscal Year: 2010....
- MOLECULAR PROPERTIES OF CARDIAC ADRENERGIC RECEPTORSRobert Lefkowitz; Fiscal Year: 1980....