Susan George

Summary

Affiliation: University of Toronto
Country: Canada

Publications

  1. ncbi request reprint Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, USA
    J Biol Chem 279:7901-8. 2004
  2. ncbi request reprint Dopamine receptor heteromeric complexes and their emerging functions
    Susan R George
    Departments of Medicine and Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada Electronic address
    Prog Brain Res 211:183-200. 2014
  3. pmc The dopamine d1-d2 receptor heteromer in striatal medium spiny neurons: evidence for a third distinct neuronal pathway in Basal Ganglia
    Melissa L Perreault
    Centre for Addiction and Mental Health, University of Toronto Toronto, ON, Canada
    Front Neuroanat 5:31. 2011
  4. pmc Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2
    Melissa L Perreault
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    PLoS ONE 7:e33348. 2012
  5. pmc Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance
    Ahmed Hasbi
    Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
    Mol Brain 4:26. 2011
  6. pmc Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base
    Lucy Skrabanek
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    BMC Bioinformatics 8:177. 2007
  7. ncbi request reprint A transmembrane domain-derived peptide inhibits D1 dopamine receptor function without affecting receptor oligomerization
    S R George
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 273:30244-8. 1998
  8. ncbi request reprint A novel dopamine receptor signaling unit in brain: heterooligomers of D1 and D2 dopamine receptors
    Susan R George
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    ScientificWorldJournal 7:58-63. 2007
  9. ncbi request reprint Blockade of G protein-coupled receptors and the dopamine transporter by a transmembrane domain peptide: novel strategy for functional inhibition of membrane proteins in vivo
    Susan R George
    Department of Pharmacology, University of Toronto, Medical Sciences Building Room 4358, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    J Pharmacol Exp Ther 307:481-9. 2003
  10. ncbi request reprint G-protein-coupled receptor oligomerization and its potential for drug discovery
    Susan R George
    Department of Pharmacology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Nat Rev Drug Discov 1:808-20. 2002

Research Grants

  1. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2004
  2. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2005
  3. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2006
  4. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2007
  5. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2009
  6. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan R George; Fiscal Year: 2010

Collaborators

Detail Information

Publications45

  1. ncbi request reprint Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, USA
    J Biol Chem 279:7901-8. 2004
    ..This discovery of apelin, AT(1), and B(2) receptors with agonist-independent nuclear translocation suggests major unanticipated roles for these receptors in cell signaling and function...
  2. ncbi request reprint Dopamine receptor heteromeric complexes and their emerging functions
    Susan R George
    Departments of Medicine and Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada Electronic address
    Prog Brain Res 211:183-200. 2014
    ..These dopamine receptor heteromers provide new insight into physiological mechanisms and pathophysiological processes involving dopamine. ..
  3. pmc The dopamine d1-d2 receptor heteromer in striatal medium spiny neurons: evidence for a third distinct neuronal pathway in Basal Ganglia
    Melissa L Perreault
    Centre for Addiction and Mental Health, University of Toronto Toronto, ON, Canada
    Front Neuroanat 5:31. 2011
    ....
  4. pmc Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2
    Melissa L Perreault
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    PLoS ONE 7:e33348. 2012
    ..This could have broad implications in understanding how dysregulation of neurotransmission within basal ganglia contributes to dopamine neuronal dysfunction...
  5. pmc Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance
    Ahmed Hasbi
    Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada
    Mol Brain 4:26. 2011
    ..Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance...
  6. pmc Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base
    Lucy Skrabanek
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
    BMC Bioinformatics 8:177. 2007
    ....
  7. ncbi request reprint A transmembrane domain-derived peptide inhibits D1 dopamine receptor function without affecting receptor oligomerization
    S R George
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 273:30244-8. 1998
    ..These findings represent the first demonstration that a peptide based on the transmembrane 6 of the D1DR may represent a novel category of noncompetitive D1DR antagonists...
  8. ncbi request reprint A novel dopamine receptor signaling unit in brain: heterooligomers of D1 and D2 dopamine receptors
    Susan R George
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    ScientificWorldJournal 7:58-63. 2007
    ..Thus, the D1-D2 heterooligomer directly links the action of dopamine to rapid calcium signaling and likely has important effects on dopamine-mediated synaptic plasticity and its functional correlates in brain...
  9. ncbi request reprint Blockade of G protein-coupled receptors and the dopamine transporter by a transmembrane domain peptide: novel strategy for functional inhibition of membrane proteins in vivo
    Susan R George
    Department of Pharmacology, University of Toronto, Medical Sciences Building Room 4358, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    J Pharmacol Exp Ther 307:481-9. 2003
    ..The disruption of the hydrophobic core architecture of membrane proteins represents a novel mechanism of achieving functional inhibition that may be possible to exploit in developing novel therapeutics...
  10. ncbi request reprint G-protein-coupled receptor oligomerization and its potential for drug discovery
    Susan R George
    Department of Pharmacology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Nat Rev Drug Discov 1:808-20. 2002
    ..This review provides a synopsis of the current thinking surrounding GPCR homo-oligomerization and hetero-oligomerization and shows how new models point towards unexplored avenues in the development of new therapies...
  11. ncbi request reprint Oligomerization of mu- and delta-opioid receptors. Generation of novel functional properties
    S R George
    Departments of Pharmacology and Medicine, University of Toronto and the Centre for Addiction and Mental Health, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 275:26128-35. 2000
    ..In this study, we provide, for the first time, evidence for the direct interaction of mu- and delta-opioid receptors to form oligomers, with the generation of novel pharmacology and G protein coupling properties...
  12. pmc D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum
    Asim J Rashid
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Proc Natl Acad Sci U S A 104:654-9. 2007
    ....
  13. ncbi request reprint Agonist-induced cell surface trafficking of an intracellularly sequestered D1 dopamine receptor homo-oligomer
    Michael M C Kong
    Department of Pharmacology, University of Toronto Medical Sciences Building Rm 4358, Toronto, ON, Canada M5S 1A8
    Mol Pharmacol 70:78-89. 2006
    ....
  14. pmc Calcium signaling cascade links dopamine D1-D2 receptor heteromer to striatal BDNF production and neuronal growth
    Ahmed Hasbi
    Centre for Addiction and Mental Health, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 106:21377-82. 2009
    ..This dopaminergic pathway regulating neuronal growth and maturation through BDNF may have considerable significance in disorders such as drug addiction, schizophrenia, and depression...
  15. pmc Dopamine D1-D2 receptor Heteromer-mediated calcium release is desensitized by D1 receptor occupancy with or without signal activation: dual functional regulation by G protein-coupled receptor kinase 2
    Vaneeta Verma
    Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 285:35092-103. 2010
    ..These results indicated that desensitization of the dopamine D1-D2 receptor heteromer-mediated signal can occur by agonist occupancy even without activation and is dually regulated by both the catalytic and RGS domains of GRK2...
  16. ncbi request reprint Dopamine receptor oligomerization visualized in living cells
    Brian F O'Dowd
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 280:37225-35. 2005
    ..Thus, we describe a novel method showing that a homogeneous receptor conformation maintains the structural integrity of oligomers, whereas conformational heterogeneity disrupts it...
  17. ncbi request reprint Using ligand-induced conformational change to screen for compounds targeting G-protein-coupled receptors
    Brian F O'Dowd
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    J Biomol Screen 12:175-85. 2007
    ..Thus, the authors have developed a cellular assay for GPCRs suitable for compound screening without requiring prior identification of an agonist or knowledge of G-protein-coupling...
  18. pmc Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis
    Philip Seeman
    Pharmacology Department, Medical Science Building, Room 4344, University of Toronto, 1 King s College Circle, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 102:3513-8. 2005
    ..If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted...
  19. ncbi request reprint Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal
    Samuel P Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 279:35671-8. 2004
    ....
  20. ncbi request reprint Novel G-protein-coupled receptor genes expressed in the brain: continued discovery of important therapeutic targets
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Medical Science Building, 8 Taddle Creek Rd Rm 4352, Toronto, Ontario M5S 1A8, Canada
    Expert Opin Ther Targets 6:185-202. 2002
    ..Equipped with proven ligand identification strategies, the characterisation of all orphan GPCRs and the exploitation of their exciting potential as targets for the discovery of novel drugs is anticipated...
  21. pmc Calcium signaling by dopamine D5 receptor and D5-D2 receptor hetero-oligomers occurs by a mechanism distinct from that for dopamine D1-D2 receptor hetero-oligomers
    Christopher H So
    Department of Pharmacology, University of Toronto, and the Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Mol Pharmacol 75:843-54. 2009
    ..Collectively, these results demonstrate that calcium signaling through D5-D2 receptor hetero-oligomers occurred through a distinct mechanism to achieve an increase in intracellular calcium levels...
  22. pmc Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms
    Ahmed Hasbi
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Curr Opin Pharmacol 10:93-9. 2010
    ..These novel receptor heteromeric complexes, for the first time, establish the link between dopamine action and rapid calcium signaling...
  23. doi request reprint Mu-opioid receptor heterooligomer formation with the dopamine D1 receptor as directly visualized in living cells
    Jason R Juhasz
    Department of Pharmacology University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Eur J Pharmacol 581:235-43. 2008
    ....
  24. ncbi request reprint Neuronal Gq/11-coupled dopamine receptors: an uncharted role for dopamine
    Asim J Rashid
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Trends Pharmacol Sci 28:551-5. 2007
    ..The importance of such a pathway is underlined by putative links between dopamine-regulated phosphoinositide signaling and several central nervous system disorders that include schizophrenia, addiction and Parkinson's disease...
  25. ncbi request reprint Distinct residues in the carboxyl tail mediate agonist-induced desensitization and internalization of the human dopamine D1 receptor
    Michael Lamey
    Departments of Pharmacology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 277:9415-21. 2002
    ..These results indicate that agonist-induced desensitization and internalization are regulated by separate and distinct serine and threonine residues within the carboxyl tail of the human dopamine D(1) receptor...
  26. ncbi request reprint Desensitization of the dopamine D1 and D2 receptor hetero-oligomer mediated calcium signal by agonist occupancy of either receptor
    Christopher H So
    Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
    Mol Pharmacol 72:450-62. 2007
    ....
  27. ncbi request reprint Family 1 G protein-coupled receptor function in the CNS. Insights from gene knockout mice
    Joanna M Karasinska
    Department of Pharmacology, University of Toronto, Medical Sciences Building, 1 King s College Circle, Room 4353, Toronto, Ontario M5S 1A8, Canada
    Brain Res Brain Res Rev 41:125-52. 2003
    ..In this review, we have listed the family 1 GPCR knockout models produced in the past decade and we have summarized the findings obtained from studies on these mice with respect to CNS function...
  28. ncbi request reprint Continued discovery of ligands for G protein-coupled receptors
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Life Sci 74:293-7. 2003
    ..Here, we briefly summarize the recent identification of neuropeptides W and B and carboxylic acid anions for their respective receptors GPR7, GPR8 and GPR40, GPR41, GPR43...
  29. ncbi request reprint Minireview: Diversity and complexity of signaling through peptidergic G protein-coupled receptors
    Asim J Rashid
    Room 4358, Medical Science Building, 1 King s College Circle, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Endocrinology 145:2645-52. 2004
    ....
  30. ncbi request reprint D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor
    Christopher H So
    Departments of Pharmacology and Medicine, University of Toronto, Toronto, Ontario, Canada
    Mol Pharmacol 68:568-78. 2005
    ....
  31. ncbi request reprint D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4
    Samuel P Lee
    Department of Pharmacology, University of Toronto, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Biochemistry 42:11023-31. 2003
    ..These results indicated that there are other sites of interaction involved in D2 receptor oligomer assembly in addition to transmembrane domain 4...
  32. pmc Restoration of amphetamine-induced locomotor sensitization in dopamine D1 receptor-deficient mice
    Mufida B El-Ghundi
    Department of Pharmacology, University of Toronto, Medical Sciences Building, 1 King s College Circle, Toronto, ON, Canada
    Psychopharmacology (Berl) 207:599-618. 2010
    ..We investigated whether experimental variables, alteration in gene expression or cholinergic input played a role in amphetamine-induced responses...
  33. ncbi request reprint Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice
    Mufida El-Ghundi
    Department of Pharmacology, University of Toronto, Medical Sciences Building, 1 King s College Circle, Toronto, Ontario M5S 1A8, Canada
    Eur J Neurosci 17:851-62. 2003
    ....
  34. doi request reprint The fate of the internalized apelin receptor is determined by different isoforms of apelin mediating differential interaction with beta-arrestin
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Biochem Biophys Res Commun 395:185-9. 2010
    ..These observations revealed a novel ligand-dependent targeting of the apelin receptor to beta-arrestin-associated and -dissociated trafficking pathways and a role for different Rab proteins to direct these pathways...
  35. ncbi request reprint Trafficking of preassembled opioid mu-delta heterooligomer-Gz signaling complexes to the plasma membrane: coregulation by agonists
    Ahmed Hasbi
    The Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Biochemistry 46:12997-3009. 2007
    ..Thus, mu-deltaOR heterooligomers form and preferentially associate with Gz to generate a signaling complex in the ER, and have a distinct agonist-internalization profile compared to either mu or delta homooligomers...
  36. ncbi request reprint Homo- and hetero-oligomerization of G protein-coupled receptors
    Samuel P Lee
    Department of Pharmacology, University of Toronto, 1 King s College Circle, M5S 1A8, Toronto, Ontario, Canada
    Life Sci 74:173-80. 2003
    ....
  37. ncbi request reprint Modification of the terminal residue of apelin-13 antagonizes its hypotensive action
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Endocrinology 146:231-6. 2005
    ..However, concomitant administration of apelin-13(F13A) (30 microg/kg) blocked hypotensive effects of apelin-13 (15 microg/kg), which revealed that apelin-13(F13A) behaved as an apelin-specific antagonist...
  38. ncbi request reprint Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation
    Joanna M Karasinska
    Department of Pharmacology, University of Toronto, Medical Sciences Building, Room 4358, 1 King s College Circle, Toronto, ON M5S 1A8, Canada
    Eur J Neurosci 22:1741-50. 2005
    ..Furthermore, alterations in pCREB levels were associated with changes in cocaine-induced locomotor activity but not reward...
  39. ncbi request reprint A cysteinyl leukotriene 2 receptor variant is associated with atopy in the population of Tristan da Cunha
    Miles D Thompson
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Pharmacogenetics 13:641-9. 2003
    ..0015). This represents the first association of a coding mutation in the CysLT2 receptor gene, located on chromosome 13q14, with the atopic phenotype found in the Tristan da Cunha population...
  40. ncbi request reprint Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity
    Dennis K Lee
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8
    Trends Pharmacol Sci 27:190-4. 2006
    ..Given its broad array of physiological roles, apelin has attracted much interest as a target for novel therapeutic research and drug design...
  41. ncbi request reprint A G protein-coupled receptor for estrogen: the end of the search?
    Ahmed Hasbi
    Departments of Pharmacology, University of Toronto, Ontario, Canada
    Mol Interv 5:158-61. 2005
    ..And what is to be made of differing accounts of GPR30's intracellular whereabouts?..
  42. ncbi request reprint Regulation of D1 dopamine receptor trafficking and signaling by caveolin-1
    Michael M C Kong
    Department of Pharmacology, University of Toronto, Medical Sciences Bldg, Rm 4358, Toronto, ON, Canada M5S 1A8
    Mol Pharmacol 72:1157-70. 2007
    ..Taken together, these data suggest that caveolae has an important role in regulating D1R turnover and signaling in brain...
  43. ncbi request reprint Discovery of a null mutation in a human trace amine receptor gene
    William B Vanti
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Genomics 82:531-6. 2003
    ..We found TA(3)-TR to be commonly expressed in all groups, with approximately 20% allele frequency. We did not find any statistically significant correlation between either disease and the presence of TA(3)-TR...
  44. ncbi request reprint A role for the distal carboxyl tails in generating the novel pharmacology and G protein activation profile of mu and delta opioid receptor hetero-oligomers
    Theresa Fan
    The Centre for Addiction and Mental Health, Ontario M5T 1R8, Canada
    J Biol Chem 280:38478-88. 2005
    ....
  45. ncbi request reprint Non-amine-based dopamine transporter (reuptake) inhibitors retain properties of amine-based progenitors
    Bertha K Madras
    Department of Psychiatry, Harvard Medical School, New England Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772 9102, USA
    Eur J Pharmacol 479:41-51. 2003
    ..These novel drugs compel a revision of current concepts of drug-monoamine transporter complex formation and open avenues for discovery of a new generation of therapeutic drugs...

Research Grants7

  1. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2004
    ..abstract_text> ..
  2. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2005
    ..abstract_text> ..
  3. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2006
    ..abstract_text> ..
  4. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2007
    ..abstract_text> ..
  5. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan George; Fiscal Year: 2009
    ....
  6. RECEPTORS MEDIATING DRUG DEPENDENCE
    Susan R George; Fiscal Year: 2010
    ....