Richard Neubig

Summary

Affiliation: University of Michigan
Country: USA

Publications

  1. pmc Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels
    Benita Sjögren
    Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Pharmacol 82:500-9. 2012
  2. pmc A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen
    Rebecca A Roof
    Department of Pharmacology, University of Michigan, 1301 MSRB III SPC 5632, 1150 W, Medical Center Dr, Ann Arbor, MI 48109, USA
    BMC Pharmacol 9:9. 2009
  3. ncbi request reprint Regulators of G protein signaling (RGS proteins): novel central nervous system drug targets
    R R Neubig
    Departments of Pharmacology and Internal Medicine Hypertension, The University of Michigan, Ann Arbor 48109 0632, USA
    J Pept Res 60:312-6. 2002
  4. doi request reprint Mind your salts: when the inactive constituent isn't
    Richard R Neubig
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
    Mol Pharmacol 78:558-9. 2010
  5. ncbi request reprint Missing links: mechanisms of protean agonism
    Richard R Neubig
    Department of Pharmacology, 1301 MSRB III, 1150 W Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
    Mol Pharmacol 71:1200-2. 2007
  6. ncbi request reprint International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology
    Richard R Neubig
    Department of Pharmacology, 1301 MSRB III Box 0632, University of Michigan, Ann Arbor, MI 48109 0632, USA
    Pharmacol Rev 55:597-606. 2003
  7. ncbi request reprint Regulators of G-protein signalling as new central nervous system drug targets
    Richard R Neubig
    Departments of Pharmacology and Internal Medicine Hypertension Division, University of Michigan, Ann Arbor, Massachusetts 48109 0632, USA
    Nat Rev Drug Discov 1:187-97. 2002
  8. ncbi request reprint Regulators of G protein signaling & drugs of abuse
    John R Traynor
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Mol Interv 5:30-41. 2005
  9. ncbi request reprint Under the microscope: single molecule symposium at the University of Michigan, 2006
    Nils G Walter
    Department of Chemistry, University of Michigan, 930 N University Avenue, Ann Arbor, MI 48109 1055, USA
    Biopolymers 85:106-14. 2007
  10. ncbi request reprint Receptor-antagonist interactions in the complexes of agouti and agouti-related protein with human melanocortin 1 and 4 receptors
    Biao Xin Chai
    Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biochemistry 44:3418-31. 2005

Collaborators

Detail Information

Publications62

  1. pmc Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels
    Benita Sjögren
    Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Pharmacol 82:500-9. 2012
    ..Our results support the concept of small-molecule modulation of RGS2 protein levels as a new strategy for cardiovascular therapy...
  2. pmc A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen
    Rebecca A Roof
    Department of Pharmacology, University of Michigan, 1301 MSRB III SPC 5632, 1150 W, Medical Center Dr, Ann Arbor, MI 48109, USA
    BMC Pharmacol 9:9. 2009
    ..We recently described a focused one-bead, one-compound (OBOC) library screen to identify peptide inhibitors of RGS4. Here we extend our observations to include another peptide with a different mechanism of action...
  3. ncbi request reprint Regulators of G protein signaling (RGS proteins): novel central nervous system drug targets
    R R Neubig
    Departments of Pharmacology and Internal Medicine Hypertension, The University of Michigan, Ann Arbor 48109 0632, USA
    J Pept Res 60:312-6. 2002
    ..Furthermore, drugs that could inhibit their activity could be useful in preventing the development of or in treating drug dependence...
  4. doi request reprint Mind your salts: when the inactive constituent isn't
    Richard R Neubig
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
    Mol Pharmacol 78:558-9. 2010
    ..Thus, pharmacologists, regulators, and clinicians should "mind their salts" in considering differences among supposedly equivalent agents...
  5. ncbi request reprint Missing links: mechanisms of protean agonism
    Richard R Neubig
    Department of Pharmacology, 1301 MSRB III, 1150 W Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
    Mol Pharmacol 71:1200-2. 2007
    ..Thus, these two important articles further solidify the concepts of functional selectivity and protean agonism and begin to define the first postreceptor step in actions of protean agonist ligands...
  6. ncbi request reprint International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology
    Richard R Neubig
    Department of Pharmacology, 1301 MSRB III Box 0632, University of Michigan, Ann Arbor, MI 48109 0632, USA
    Pharmacol Rev 55:597-606. 2003
    ..IX. Recommendations on terms and symbols in quantitative pharmacology. Pharmacol Rev 47:255-266)...
  7. ncbi request reprint Regulators of G-protein signalling as new central nervous system drug targets
    Richard R Neubig
    Departments of Pharmacology and Internal Medicine Hypertension Division, University of Michigan, Ann Arbor, Massachusetts 48109 0632, USA
    Nat Rev Drug Discov 1:187-97. 2002
    ..The diversity of RGS proteins with highly localized and dynamically regulated distributions in brain makes them attractive targets for pharmacotherapy of central nervous system disorders...
  8. ncbi request reprint Regulators of G protein signaling & drugs of abuse
    John R Traynor
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Mol Interv 5:30-41. 2005
    ..Finally, we consider if RGS proteins represent viable targets for drug abuse medications...
  9. ncbi request reprint Under the microscope: single molecule symposium at the University of Michigan, 2006
    Nils G Walter
    Department of Chemistry, University of Michigan, 930 N University Avenue, Ann Arbor, MI 48109 1055, USA
    Biopolymers 85:106-14. 2007
    ....
  10. ncbi request reprint Receptor-antagonist interactions in the complexes of agouti and agouti-related protein with human melanocortin 1 and 4 receptors
    Biao Xin Chai
    Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biochemistry 44:3418-31. 2005
    ....
  11. ncbi request reprint Fluorescence analysis of receptor-G protein interactions in cell membranes
    Noune A Sarvazyan
    Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109 0632, USA
    Biochemistry 41:12858-67. 2002
    ..Thus flow cytometry permits quantiatitive and real-time assessments of protein-protein interactions in complex membrane environments...
  12. ncbi request reprint Endogenous RGS protein action modulates mu-opioid signaling through Galphao. Effects on adenylyl cyclase, extracellular signal-regulated kinases, and intracellular calcium pathways
    Mary J Clark
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109 0632, USA
    J Biol Chem 278:9418-25. 2003
    ....
  13. ncbi request reprint RGS-insensitive G-protein mutations to study the role of endogenous RGS proteins
    Ying Fu
    Department of Pharmacology, University of Michigan, Ann Arbor 48105, USA
    Methods Enzymol 389:229-43. 2004
    ..This will reveal the full extent of RGS regulation and will not be confounded by redundancy in the function of multiple RGS proteins...
  14. ncbi request reprint Affinity assays using fluorescence anisotropy with capillary electrophoresis separation
    Rebecca J Whelan
    Department of Chemistry and Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    Anal Chem 76:7380-6. 2004
    ..FACE affinity assay is envisioned as a method that can quantify selected binding partners and screen complex samples for compounds that possess affinity for a particular small molecule that is used as a probe...
  15. pmc Thinking outside of the "RGS box": new approaches to therapeutic targeting of regulators of G protein signaling
    Benita Sjögren
    Department of Pharmacology, University of Michigan, 1150 W Medical Center Dr, MSRB III, Ann Arbor, MI 48109, USA
    Mol Pharmacol 78:550-7. 2010
    ..Because several RGS proteins are rapidly degraded by the N-end rule pathway, finding ways to stabilize them may prove to be an effective way to enhance RGS protein function...
  16. pmc Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins
    Levi L Blazer
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    Mol Pharmacol 78:524-33. 2010
    ..CCG-63802 and related analogs represent a useful step toward the development of chemical tools for the study of RGS physiology...
  17. ncbi request reprint Endogenous RGS proteins and Galpha subtypes differentially control muscarinic and adenosine-mediated chronotropic effects
    Ying Fu
    Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA
    Circ Res 98:659-66. 2006
    ..Thus, alterations in RGS function may play a role in pathophysiological processes and RGS proteins could represent novel cardiovascular therapeutic targets...
  18. pmc Microfabricated channel array electrophoresis for characterization and screening of enzymes using RGS-G protein interactions as a model system
    Jian Pei
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109 1055, USA
    Anal Chem 80:5225-31. 2008
    ..Both designs showed excellent reproducibility of peak migration time and peak area. Relative standard deviations of normalized peak area of enzymatic product BODIPY-GDP were 5% and 11%, respectively, in the 16- and 36-channel designs...
  19. pmc Regulator of G protein signaling protein suppression of Galphao protein-mediated alpha2A adrenergic receptor inhibition of mouse hippocampal CA3 epileptiform activity
    Brianna L Goldenstein
    Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202 9037, USA
    Mol Pharmacol 75:1222-30. 2009
    ..This suggests a possible role for RGS inhibitors or selective alpha(2A)AR agonists as a novel antiepileptic drug therapy...
  20. ncbi request reprint Mutagenesis and peptide analysis of the DRY motif in the alpha2A adrenergic receptor: evidence for alternate mechanisms in G protein-coupled receptors
    Duane A Chung
    Biophysics Research Division, The University of Michigan, Ann Arbor, MI 48109, USA
    Biochem Biophys Res Commun 293:1233-41. 2002
    ..These results indicate that the alpha2A AR does not follow the conventional GPCR mechanistic paradigm with respect to the function of the DRY motif...
  21. ncbi request reprint Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells
    Qin Wang
    Department of Pharmacology, The University of Michigan, Ann Arbor 48109 0632, USA
    J Biol Chem 277:24949-58. 2002
    ....
  22. pmc A juxtamembrane mutation in the N terminus of the dopamine transporter induces preference for an inward-facing conformation
    Bipasha Guptaroy
    Department of Pharmacology, 2220E MSRBIII, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
    Mol Pharmacol 75:514-24. 2009
    ..The mechanism underlying the important functional role of Thr62 in hDAT activity suggested by these findings is examined in a structural context using dynamic simulations of a three-dimensional molecular model of DAT...
  23. pmc Assembly of high order G alpha q-effector complexes with RGS proteins
    Aruna Shankaranarayanan
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    J Biol Chem 283:34923-34. 2008
    ....
  24. ncbi request reprint Capillary electrophoresis assay for G protein-coupled receptor-mediated GTPase activity
    Emily E Jameson
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    Anal Chem 79:1158-63. 2007
    ..It is envisioned that this technique could be used for screening for novel GPCR ligands or other G protein signaling modifiers...
  25. doi request reprint Small molecule protein-protein interaction inhibitors as CNS therapeutic agents: current progress and future hurdles
    Levi L Blazer
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Neuropsychopharmacology 34:126-41. 2009
    ..In particular, we will focus upon recent work towards developing small molecule inhibitors of amyloid-beta and alpha-synuclein aggregation, inhibitors of critical components of G-protein-signaling pathways, and PDZ domain inhibitors...
  26. pmc Novel peptide ligands of RGS4 from a focused one-bead, one-compound library
    Rebecca A Roof
    Department of Pharmacology, University of Michigan, 1301 MSRB III SPC5632, Ann Arbor, MI 48103, USA
    Chem Biol Drug Des 72:111-9. 2008
    ..Peptide 2 has been modeled to fit in the same binding pocket predicted for YJ34 but in the reverse orientation...
  27. ncbi request reprint A spatial focusing model for G protein signals. Regulator of G protein signaling (RGS) protien-mediated kinetic scaffolding
    Huailing Zhong
    Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109 0632, USA
    J Biol Chem 278:7278-84. 2003
    ....
  28. pmc Polyplexed flow cytometry protein interaction assay: a novel high-throughput screening paradigm for RGS protein inhibitors
    David L Roman
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biomol Screen 14:610-9. 2009
    ..Subsequent deconvolution of the compounds mixtures verified the identification of active compounds at specific RGS targets in their mixtures using the polyplexed FCPIA method...
  29. pmc Differential modulation of mu-opioid receptor signaling to adenylyl cyclase by regulators of G protein signaling proteins 4 or 8 and 7 in permeabilised C6 cells is Galpha subtype dependent
    Jeffery N Talbot
    Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA
    J Neurochem 112:1026-34. 2010
    ....
  30. pmc Use of flow cytometric methods to quantify protein-protein interactions
    Levi L Blazer
    Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan, USA
    Curr Protoc Cytom . 2010
    ..An adaptation of this method that is compatible for high-throughput screening is also provided...
  31. ncbi request reprint Endogenous regulator of G protein signaling proteins suppress Galphao-dependent, mu-opioid agonist-mediated adenylyl cyclase supersensitization
    Mary J Clark
    Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan 48109 0632, USA
    J Pharmacol Exp Ther 310:215-22. 2004
    ..These results demonstrate a role for Galphao in adenylyl cyclase supersensitization after mu-agonist exposure and show that this action is modulated by endogenous RGS proteins...
  32. ncbi request reprint Depicting a protein's two faces: GPCR classification by phylogenetic tree-based HMMs
    Bin Qian
    Biophysics Research Division, University of Michigan, Ann Arbor, MI 48105, USA
    FEBS Lett 554:95-9. 2003
    ..In this study we used the method to generate common features of G protein-coupled receptors (GPCRs). The profile generated by T-HMM gives high accuracy in GPCR function classification, both by ligand and by coupled G protein...
  33. ncbi request reprint Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of Goalpha
    Yu Shangguan
    Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA
    J Neurochem 86:1006-14. 2003
    ..These results suggest that diminished inhibitory G protein function observed in DRGs neurons from diabetic rats involves an isoform-specific PKC-dependent pathway...
  34. doi request reprint Regulators of G protein signaling proteins as targets for drug discovery
    Benita Sjögren
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA
    Prog Mol Biol Transl Sci 91:81-119. 2010
    ..This chapter gives an overview of what is currently known about biological functions of RGS proteins based on in vivo and in vitro data. We also summarize the current status in targeting RGS proteins in drug discovery...
  35. pmc Isoflurane-induced changes in righting response and breathing are modulated by RGS proteins
    Eduardo E Icaza
    Departments of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109 5615, USA
    Anesth Analg 109:1500-5. 2009
    ....
  36. pmc Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423
    CHRIS R EVELYN
    Department of Pharmacology, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109, USA
    Bioorg Med Chem Lett 20:665-72. 2010
    ..Both compounds were also capable of inhibiting cell invasion with equal efficacy to 1 but with less attendant cytotoxicity...
  37. ncbi request reprint NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix
    Duane A Chung
    Biophysics Research Division and Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    Biochemistry 41:3596-604. 2002
    ..These data should lead to more accurate models of the intracellular surface of GPCRs and of receptor-mediated G protein activation...
  38. pmc High-throughput screening for small-molecule inhibitors of LARG-stimulated RhoA nucleotide binding via a novel fluorescence polarization assay
    CHRIS R EVELYN
    Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan 48109 0632, USA
    J Biomol Screen 14:161-72. 2009
    ..In addition, the fluorescence polarization guanine nucleotide-binding assay described here should serve as a useful approach for both high-throughput screening and general biological applications...
  39. doi request reprint In vitro protein kinase activity measurement by flow cytometry
    Donald J Bernsteel
    Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109, USA
    Anal Biochem 383:180-5. 2008
    ..We also discuss conditions necessary to optimize measurement of the activity of several kinases in a single sample...
  40. pmc RGS inhibition at G(alpha)i2 selectively potentiates 5-HT1A-mediated antidepressant effects
    Jeffery N Talbot
    Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 107:11086-91. 2010
    ..By selectively enhancing the beneficial effects of serotonin, inhibition of RGS proteins represents a therapeutic approach for the treatment of mood disorders...
  41. pmc GNAI2 and regulators of G protein signaling as a potential Noonan syndrome mechanism
    Xinyan Huang
    Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109, USA
    Med Hypotheses 73:56-9. 2009
    ..This suggests a novel set of candidate genes for NS (GNAI2 and RGS proteins) and if validated could have important implications for therapy as well...
  42. ncbi request reprint Expression of novel splice variants of the G protein subunit, Go alpha, is tissue-specific and age-dependent in the rat
    Jong Hyeon Yoo
    Department of Internal Medicine, Gastrointestinal Peptide Research Center, University of Michigan, Ann Arbor 48109 0368, USA
    Gene 296:249-55. 2002
    ..The age-dependent and tissue-specific expression of the G(o)alpha1 splice variants presage a broader functional role than has been observed historically with G(o)...
  43. ncbi request reprint Detection of G proteins by affinity probe capillary electrophoresis using a fluorescently labeled GTP analogue
    Emily E Jameson
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    Anal Chem 75:4297-304. 2003
    ..Additionally, the capability of the technique to detect several G proteins based on their binding to BGTPgammaS was demonstrated with assays for Galpha and Galpha(i1) and for Ras and Rab3A...
  44. ncbi request reprint Dimerization in aminergic G-protein-coupled receptors: application of a hidden-site class model of evolution
    Orkun S Soyer
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biochemistry 42:14522-31. 2003
    ..On the basis of these findings, we propose an experimentally testable dimerization mechanism, involving interactions among different combinations of these helices in different families of aminergic GPCRs...
  45. ncbi request reprint Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells
    Qin Wang
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 279:28831-4. 2004
    ..Suppression of p115rhoGEF had no effect. Thus different rhoGEFs (LARG and PDZrhoGEF) mediate downstream rho signaling by the thrombin and LPA receptors...
  46. ncbi request reprint Ribozyme- and siRNA-mediated suppression of RGS-containing RhoGEF proteins
    Qin Wang
    Department of Pharmacology, University of Michigan, Ann Arbor 48109, USA
    Methods Enzymol 389:244-65. 2004
    ..Also, the three siRNAs targeting LARG, PDZ-RhoGEF, and p115-RhoGEF are able to discriminate the closely related sequences within this RGS-RhoGEF gene family...
  47. ncbi request reprint Structure-based design, synthesis, and activity of peptide inhibitors of RGS4 GAP activity
    Yafei Jin
    Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109, USA
    Methods Enzymol 389:266-77. 2004
    ..These compounds should prove useful for elucidating RGS-mediated activity and serve as a starting point for the development of a novel class of therapeutic agent...
  48. ncbi request reprint Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma
    Bradley S Henson
    Department of Oral Medicine, Pathology, and Oncology, University of Michigan School of Dentistry, Ann Arbor, 48109 0506, USA
    J Biol Chem 280:22564-71. 2005
    ..GALR1s inhibitory effects on proliferation in epithelial cells raises the possibility that inactivation or disregulation of this receptor can lead to uncontrolled proliferation and neoplastic transformation...
  49. ncbi request reprint Mechanism of action and structural requirements of constrained peptide inhibitors of RGS proteins
    Rebecca A Roof
    Department of Pharmacology, 1150 W Medical Center Dr, University of Michigan, Ann Arbor, MI 48109, USA
    Chem Biol Drug Des 67:266-74. 2006
    ..These data support the proposed mechanism of action of peptide RGS inhibitors, demonstrate their action in native cells, and provide a starting point for the design of RGS inhibitor drugs...
  50. pmc Pleiotropic phenotype of a genomic knock-in of an RGS-insensitive G184S Gnai2 allele
    Xinyan Huang
    Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109, USA
    Mol Cell Biol 26:6870-9. 2006
    ..Thus, loss of RGS actions at Galpha(i2) produces a dramatic and pleiotropic phenotype which is more evident than the phenotype seen for individual RGS protein knockouts...
  51. ncbi request reprint Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay
    David L Roman
    Department of Pharmacology, University of Michigan Medical School, 1150 W Medical Center Drive, 1303 MSRB III, Ann Arbor, MI 41809, USA
    Mol Pharmacol 71:169-75. 2007
    ..Thus, we demonstrate the feasibility of targeting RGS/Galpha protein-protein interactions with small molecules as a novel means to modulate GPCR-mediated signaling processes...
  52. ncbi request reprint Real-time detection of basal and stimulated G protein GTPase activity using fluorescent GTP analogues
    Emily E Jameson
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 280:7712-9. 2005
    ..The unexpected levels of BGTPgammaS hydrolysis detected suggest that caution should be used when interpreting data from fluorescence assays with this probe...
  53. ncbi request reprint N-terminal residues control proteasomal degradation of RGS2, RGS4, and RGS5 in human embryonic kidney 293 cells
    Johannes Bodenstein
    Department of Pharmacology, 1301 MSRB III Box 0632, 1150 W Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109 0632, USA
    Mol Pharmacol 71:1040-50. 2007
    ..Thus, proteasomal regulation of RGS expression in HEK293 cells strongly controls RGS function and a novel RGS2 mutation with decreased protein expression could be relevant to the pathophysiology of hypertension in humans...
  54. ncbi request reprint Endogenous RGS proteins modulate SA and AV nodal functions in isolated heart: implications for sick sinus syndrome and AV block
    Ying Fu
    Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109 0632, USA
    Am J Physiol Heart Circ Physiol 292:H2532-9. 2007
    ..The severe carbachol-induced sinus bradycardia in Galpha(i2)G184S mice suggests a possible role for alterations of Galpha(i2) or RGS proteins in sick sinus syndrome and pathological AV block...
  55. ncbi request reprint Inverse agonist activity of agouti and agouti-related protein
    Biao Xin Chai
    Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109 0682, USA
    Peptides 24:603-9. 2003
    ..These data shed new light on the determinants and mechanism of inverse agonism at the MC4R...
  56. ncbi request reprint Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs
    Susanne Lutz
    Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Maybachstrasse 14, D 68169 Mannheim, Germany
    Science 318:1923-7. 2007
    ..We propose that this structure represents the crux of an ancient signal transduction pathway that is expected to be important in an array of physiological processes...
  57. ncbi request reprint The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state
    G Enrico Rovati
    Laboratory of Molecular Pharmacology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
    Mol Pharmacol 71:959-64. 2007
    ..Thus, it is essential to look beyond the rhodopsin ground-state model of conformational activation to clarify the role of this highly conserved triplet in GPCR activation and function...
  58. pmc And the winner is ... RGS4!
    Richard R Neubig
    Circ Res 103:444-6. 2008
  59. ncbi request reprint Ligand-receptor-G-protein molecular assemblies on beads for mechanistic studies and screening by flow cytometry
    Peter C Simons
    Department of Pathology and Cancer Center, University of New Mexico HSC, Albuquerque, NM 87131, USA
    Mol Pharmacol 64:1227-38. 2003
    ....
  60. ncbi request reprint Regions in the G protein gamma subunit important for interaction with receptors and effectors
    Chang Seon Myung
    Department of Pharmacology, College of Pharmacy, Chungnam National University Daejeon, Korea
    Mol Pharmacol 69:877-87. 2006
    ..The results indicate that both the N- and C-terminal regions of the gamma subunit impart specificity to receptor and effector interactions...
  61. ncbi request reprint Stimulation of cellular signaling and G protein subunit dissociation by G protein betagamma subunit-binding peptides
    Farida Goubaeva
    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, New York 14642, USA
    J Biol Chem 278:19634-41. 2003
    ..These data suggest a novel mechanism by which selective betagamma-binding peptides can release G protein betagamma subunits from heterotrimers to stimulate G protein pathways in cells...
  62. ncbi request reprint Real-time analysis of ternary complex on particles: direct evidence for partial agonism at the agonist-receptor-G protein complex assembly step of signal transduction
    Peter C Simons
    Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    J Biol Chem 279:13514-21. 2004
    ..The assemblies can be further generalized to other G protein coupled receptor protein-protein interactions...

Research Grants42

  1. Physiological functions of G-alpha-i/o and control by regulators of G protein sig
    Richard R Neubig; Fiscal Year: 2010
    ..By improving those therapeutically useful signals at the expense of signals leading to side effects, we can produce better medicines or can make existing medicines better tolerated. ..
  2. STRUCTURAL BASIS OF RECEPTOR/G PROTEIN FUNCTION
    Richard Neubig; Fiscal Year: 2004
    ..This work should greatly improve our understanding of the structural and mechanistic basis of RG coupling and should facilitate the design of drugs that target particular G protein subunit combinations. ..
  3. Biophysical Studies of G Protein Activation/Deactivation
    Richard Neubig; Fiscal Year: 2003
    ..The studies in this proposal should permit a better understanding of rapid G protein activation and deactivation mechanisms and will explore the potential of RGS proteins as a novel target of drug action. ..
  4. Multiplexed flow cytometry screens for RGS inhibitors
    Richard Neubig; Fiscal Year: 2006
    ..The ultimate aim of this project is the identification of selective small molecule inhibitors of RGS action. This will provide important chemical tools and accelerate the development of novel therapeutics. ..
  5. Biophysical Studies of G Protein Activation/Deactivation
    Richard Neubig; Fiscal Year: 2006
    ..The studies in this proposal should permit a better understanding of rapid G protein activation and deactivation mechanisms and will explore the potential of RGS proteins as a novel target of drug action. ..
  6. Design of Small Molecules Acting at Regulators of G Protein Signaling
    Richard R Neubig; Fiscal Year: 2010
    ..This project will provide the initial steps and proof of principle for medications development targeting RGS proteins - a key modulator of signaling related to drug abuse. ..
  7. Pharmacological Targeting of Regulators of G Protein Signaling
    Richard Neubig; Fiscal Year: 2009
    ..The ultimate goal is to define their potential as therapeutic targets in heart disease, obesity, and diabetes. ..
  8. Multiplexed flow cytometry screens for RGS inhibitors
    Richard Neubig; Fiscal Year: 2007
    ..The ultimate aim of this project is the identification of selective small molecule inhibitors of RGS action. This will provide important chemical tools and accelerate the development of novel therapeutics. ..
  9. Design of Small Molecules Acting at Regulators of G Protein Signaling
    Richard Neubig; Fiscal Year: 2007
    ..This project will provide the initial steps and proof of principle for medications development targeting RGS proteins - a key modulator of signaling related to drug abuse. ..
  10. Pharmacological Targeting of Regulators of G Protein Signaling
    Richard Neubig; Fiscal Year: 2007
    ..The ultimate goal is to define their potential as therapeutic targets in heart disease, obesity, and diabetes. ..
  11. BIOPHYSICAL STUDIES OF G PROTEIN ACTIVATION
    Richard Neubig; Fiscal Year: 2001
    ....
  12. PEPTIDE MODULATORS OF G PROTEIN FUNCTION
    Richard Neubig; Fiscal Year: 2000
    ..The specificity of these "drugs" will be tested in cell culture with the aim of future use in gene therapy approaches to cardiovascular disease. ..
  13. PEPTIDE MODULATORS OF G PROTEIN FUNCTION
    Richard Neubig; Fiscal Year: 1993
    ....
  14. RAPID KINETICS OF A2 ADRENERGIC RECEPTOR ACTIVATION
    Richard Neubig; Fiscal Year: 1993
    ..More generally, the information on receptor-G protein coupling is applicable to a wide range of biological signalling mechanisms including adenylate cyclase, inositol lipid metabolism and regulation of ion channels...