T Harden

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. ncbi request reprint Purification and G protein subunit regulation of a phospholipase C-beta from Xenopus laevis oocytes
    T M Filtz
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 271:31121-6. 1996
  2. pmc A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils
    Matthew O Barrett
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Mol Pharmacol 84:41-9. 2013
  3. ncbi request reprint A fusion protein of the human P2Y(1) receptor and NTPDase1 exhibits functional activities of the native receptor and ectoenzyme and reduced signaling responses to endogenously released nucleotides
    Claudia Alvarado-Castillo
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Mol Pharmacol 62:521-8. 2002
  4. pmc Phospholipase C isozymes as effectors of Ras superfamily GTPases
    T Kendall Harden
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    J Lipid Res 50:S243-8. 2009
  5. pmc Signalling and pharmacological properties of the P2Y receptor
    T K Harden
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Acta Physiol (Oxf) 199:149-60. 2010
  6. ncbi request reprint Regulation of phospholipase C isozymes by ras superfamily GTPases
    T Kendall Harden
    Departments of Pharmacology, Biochemistry and Biophysics, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Annu Rev Pharmacol Toxicol 46:355-79. 2006
  7. ncbi request reprint Regulation of P2Y1 receptor-mediated signaling by the ectonucleoside triphosphate diphosphohydrolase isozymes NTPDase1 and NTPDase2
    Claudia Alvarado-Castillo
    Department of Pharmacology, University of North Carolina School of Medicine, CB 7365, Chapel Hill, NC 27599 7365, USA
    Mol Pharmacol 67:114-22. 2005
  8. ncbi request reprint Quantification of isozyme-specific activation of phospholipase C-beta2 by Rac GTPases and phospholipase C-epsilon by Rho GTPases in an intact cell assay system
    David M Bourdon
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, USA
    Methods Enzymol 406:489-99. 2006
  9. ncbi request reprint Application of RGS box proteins to evaluate G-protein selectivity in receptor-promoted signaling
    Melinda D Hains
    Department of Pharmacology, The University of North Carolina School of Medicine, Chapel Hill 27599, USA
    Methods Enzymol 389:71-88. 2004
  10. pmc [32P]2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate ([32P]MRS2500), a novel radioligand for quantification of native P2Y1 receptors
    Dayle Houston
    Department of Pharmacology, University of North Carolina School of Medicine, CB 7365 Chapel Hill, NC 27599, USA
    Br J Pharmacol 147:459-67. 2006

Research Grants

  1. REGULATION OF PHOSPHOLIPASE C
    T Harden; Fiscal Year: 2002
  2. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2004
  3. G protein signal integration by multifunctional proteins
    T Harden; Fiscal Year: 2006
  4. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2007
  5. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2009
  6. P2Y-PURINERGIC RECEPTORS
    T Kendall Harden; Fiscal Year: 2010
  7. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2000
  8. MUSCARINIC RECEPTOR SUBTYPES ON CULTURED CELLS
    T Harden; Fiscal Year: 1991
  9. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 1993
  10. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2009

Collaborators

  • K A Jacobson
  • EDUARDO RODOLFO LAZAROWSKI
  • DAVID SIDEROVSKI
  • Robert Nicholas
  • Dayle Houston
  • Channing Der
  • Francis S Willard
  • KLAUS MICHAEL HAHN
  • R Juliano
  • Stefano Costanzi
  • Adam Shutes
  • Natalia Mitin
  • V J Watts
  • Marco Cattaneo
  • JOSE BOYER
  • Malin Malmsjo
  • Herbert Zimmermann
  • John Sondek
  • Savitri Maddileti
  • Jason T Snyder
  • Gary L Waldo
  • Michele R Wing
  • Hyojin Ko
  • Yixing Zhou
  • Jason P Seifert
  • Rhonda L Carter
  • Ingrid P Fricks
  • Hak Sung Kim
  • Mark R Jezyk
  • Stephanie N Hicks
  • Pedro Besada
  • Erik T Bodor
  • Shelley B Hooks
  • Svetlana Gershburg
  • Matthew O Barrett
  • Melinda D Hains
  • Matthew L Cheever
  • Claudia Alvarado-Castillo
  • Andrei A Ivanov
  • R Gnana Ravi
  • David M Bourdon
  • Michihiro Ohno
  • James Corbitt
  • Jesús Mateo
  • Jiyoung Y Cha
  • Alex U Singer
  • Kevin D Healy
  • Serge Van Calenbergh
  • Liesbet Cosyn
  • Ingrid Fricks
  • Samuel C Wolff
  • Christopher A Johnston
  • Ai Dong Qi
  • Mariya Chhatriwala
  • Christopher L Herold
  • Myoung Goo Kim
  • Victor E Marquez
  • Mingyan Hou
  • David Erlinge
  • P Suresh Jayasekara
  • Juliana I Sesma
  • Christopher B Ball
  • Takeharu Kawano
  • Kazuhito Tsuboi
  • Craig Montell
  • Tohru Kozasa
  • Xiaoyue Wang
  • Tiffany K Ricks
  • Lauren E Burianek
  • Arijit Das
  • Loredana Cappellacci
  • Louis Hodgson
  • Sonia de Castro
  • Yung Jue Bang
  • Palmarisa Franchetti
  • Riccardo Petrelli
  • Tai Young Kim
  • Mario Grifantini
  • Gilles Gosselin
  • Christophe Mathé
  • Svetlana Gershberg
  • Earl B Edwards
  • Julien Gagneron
  • David K Worthylake
  • Dae Hong Shin
  • Miller B Jones
  • Zoey Fredericks
  • J Kevin Ramer
  • Rainer Blaesius
  • Karen Vastmans

Detail Information

Publications58

  1. ncbi request reprint Purification and G protein subunit regulation of a phospholipase C-beta from Xenopus laevis oocytes
    T M Filtz
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 271:31121-6. 1996
    ....
  2. pmc A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils
    Matthew O Barrett
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Mol Pharmacol 84:41-9. 2013
    ..In summary, this work establishes PPTN as a highly selective high-affinity antagonist of the P2Y14-R that is useful for interrogating the action of this receptor in physiologic systems...
  3. ncbi request reprint A fusion protein of the human P2Y(1) receptor and NTPDase1 exhibits functional activities of the native receptor and ectoenzyme and reduced signaling responses to endogenously released nucleotides
    Claudia Alvarado-Castillo
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Mol Pharmacol 62:521-8. 2002
    ..Although marked elevation of inositol phosphate levels occurred with wild-type P2Y(1) receptor expression, levels in cells expressing the fusion protein were not different from those in wild-type CHO-K1 cells...
  4. pmc Phospholipase C isozymes as effectors of Ras superfamily GTPases
    T Kendall Harden
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    J Lipid Res 50:S243-8. 2009
    ..High resolution three-dimensional structures of phospholipase C isozymes also are beginning to shed light on their mechanism of activation...
  5. pmc Signalling and pharmacological properties of the P2Y receptor
    T K Harden
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Acta Physiol (Oxf) 199:149-60. 2010
    ..This receptor historically was thought to be activated selectively by UDP-glucose and other UDP-sugars. However, UDP is also a very potent agonist of this receptor, and may prove to be one of its most important cognate activators...
  6. ncbi request reprint Regulation of phospholipase C isozymes by ras superfamily GTPases
    T Kendall Harden
    Departments of Pharmacology, Biochemistry and Biophysics, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Annu Rev Pharmacol Toxicol 46:355-79. 2006
    ....
  7. ncbi request reprint Regulation of P2Y1 receptor-mediated signaling by the ectonucleoside triphosphate diphosphohydrolase isozymes NTPDase1 and NTPDase2
    Claudia Alvarado-Castillo
    Department of Pharmacology, University of North Carolina School of Medicine, CB 7365, Chapel Hill, NC 27599 7365, USA
    Mol Pharmacol 67:114-22. 2005
    ....
  8. ncbi request reprint Quantification of isozyme-specific activation of phospholipase C-beta2 by Rac GTPases and phospholipase C-epsilon by Rho GTPases in an intact cell assay system
    David M Bourdon
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, USA
    Methods Enzymol 406:489-99. 2006
    ....
  9. ncbi request reprint Application of RGS box proteins to evaluate G-protein selectivity in receptor-promoted signaling
    Melinda D Hains
    Department of Pharmacology, The University of North Carolina School of Medicine, Chapel Hill 27599, USA
    Methods Enzymol 389:71-88. 2004
    ....
  10. pmc [32P]2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate ([32P]MRS2500), a novel radioligand for quantification of native P2Y1 receptors
    Dayle Houston
    Department of Pharmacology, University of North Carolina School of Medicine, CB 7365 Chapel Hill, NC 27599, USA
    Br J Pharmacol 147:459-67. 2006
    ..Taken together, these data illustrate the synthesis and characterization of a novel P2Y1 receptor radioligand and its utility for examining P2Y1 receptor expression in native mammalian tissues...
  11. ncbi request reprint PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling
    Michele R Wing
    Department of Pharmacology University of North Carolina School of Medicine Chapel Hill, NC 27599, USA
    Mol Interv 3:273-80. 2003
    ..Thus, PLC-epsilon is a multifunctional nexus protein that senses and mediates crosstalk between heterotrimeric and small GTPase signaling pathways...
  12. ncbi request reprint RGS6, RGS7, RGS9, and RGS11 stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity
    Shelley B Hooks
    Department of Pharmacology, University of North Carolina, Chapel Hill 27599, USA
    J Biol Chem 278:10087-93. 2003
    ..Therefore, R7 family RGS proteins are G(i) family-selective GAPs with potentially important differences in activities...
  13. pmc Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex
    Gary L Waldo
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Science 330:974-80. 2010
    ..Mutations within this domain dramatically delay signal termination in vitro and in vivo. Consequently, this work suggests a dynamic catch-and-release mechanism used to sharpen spatiotemporal signals mediated by diverse sensory inputs...
  14. ncbi request reprint Regulation of PLCbeta isoforms by Rac
    Jason T Snyder
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, USA
    Methods Enzymol 406:272-80. 2006
    ..The experimental format described is also readily adaptable toward characterizing guanine nucleotide-dependent binding events of both small and heterotrimeric G proteins with various classes of GTPase regulatory proteins...
  15. pmc Molecular cloning and characterization of PLC-eta2
    Yixing Zhou
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Biochem J 391:667-76. 2005
    ..Co-expression of PLC-eta2 with Gbeta1gamma2 dimers of heterotrimeric G-proteins resulted in marked stimulation of inositol lipid hydrolysis. Thus PLC-eta2 may in part function downstream of G-protein-coupled receptors...
  16. pmc Quantification of Gi-mediated inhibition of adenylyl cyclase activity reveals that UDP is a potent agonist of the human P2Y14 receptor
    Rhonda L Carter
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
    Mol Pharmacol 76:1341-8. 2009
    ..We conclude that UDP is an important cognate agonist of the human P2Y14 receptor...
  17. pmc DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms
    Kevin D Healy
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599 7295, USA
    Mol Carcinog 47:326-37. 2008
    ..Combined, these studies provide information on the mechanism of DLC-1 function and regulation, and further support the role of DLC-1 tumor suppression in NSCLC...
  18. pmc Induction of novel agonist selectivity for the ADP-activated P2Y1 receptor versus the ADP-activated P2Y12 and P2Y13 receptors by conformational constraint of an ADP analog
    Mariya Chhatriwala
    University of North Carolina, School of Medicine, Department of Pharmacology, CB 7365, Chapel Hill, NC 27599 7365, USA
    J Pharmacol Exp Ther 311:1038-43. 2004
    ....
  19. ncbi request reprint The pleckstrin homology domain of phospholipase C-beta2 as an effector site for Rac
    Jason T Snyder
    Department of Pharmacology, The University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 278:21099-104. 2003
    ..Together, these findings present a quantitative evaluation of the direct interactions between Rac GTPases and PLC-beta isozymes and define a novel role for the PH domain of PLC-beta2 as a putative effector site for Rac GTPases...
  20. ncbi request reprint Direct activation of phospholipase C-epsilon by Rho
    Michele R Wing
    Department of Pharmacology, The Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 278:41253-8. 2003
    ....
  21. pmc Dual activation of phospholipase C-epsilon by Rho and Ras GTPases
    Jason P Seifert
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 283:29690-8. 2008
    ..These results indicate that PLC-epsilon can be directly and concomitantly activated by both RhoA and individual Ras GTPases resulting in diverse upstream control of signaling cascades downstream of PLC-epsilon...
  22. ncbi request reprint Galpha12/13- and rho-dependent activation of phospholipase C-epsilon by lysophosphatidic acid and thrombin receptors
    Melinda D Hains
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7365, USA
    Mol Pharmacol 69:2068-75. 2006
    ..These studies illustrate that specific LPA and thrombin receptors promote inositol lipid signaling via activation of Galpha(12/13) and Rho...
  23. pmc Development of selective high affinity antagonists, agonists, and radioligands for the P2Y1 receptor
    Dayle Houston
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Comb Chem High Throughput Screen 11:410-9. 2008
    ..A similar rational approach is being applied to develop selective ligands for other subtypes of P2Y receptors...
  24. pmc General and versatile autoinhibition of PLC isozymes
    Stephanie N Hicks
    Department of Pharmacology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
    Mol Cell 31:383-94. 2008
    ..Similar regulation occurs in other PLC members, and a general mechanism of interfacial activation at membranes is presented that provides a unifying framework for PLC activation by diverse stimuli...
  25. ncbi request reprint A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q
    Alex U Singer
    Department of Pharmacology, The University of North Carolina at Chapel Hill, North Carolina 27599, USA
    Nat Struct Biol 9:32-6. 2002
    ..Effector dimerization, as highlighted by PLC-betas, provides a viable mechanism for regulating signaling cascades linked to heterotrimeric G proteins...
  26. pmc 2-Chloro N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate is a selective high affinity P2Y(1) receptor antagonist
    Jose L Boyer
    Department of Pharmacology, University of North Carolina School of Medicine, CB7365, Chapel Hill, North Carolina, NC 27599, USA
    Br J Pharmacol 135:2004-10. 2002
    ..6. Taken together these results illustrate selective high affinity antagonism of the P2Y(1) receptor by a non-nucleotide molecule that should prove useful for pharmacological delineation of this receptor in various tissues...
  27. ncbi request reprint Purification and functional reconstitution of the human P2Y12 receptor
    Erik T Bodor
    Department of Pharmacology, University of North Carolina Chapel Hill, Chapel Hill, NC 27599 7365, USA
    Mol Pharmacol 64:1210-6. 2003
    ....
  28. ncbi request reprint RhoA activates purified phospholipase C-epsilon by a guanine nucleotide-dependent mechanism
    Jason P Seifert
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 279:47992-7. 2004
    ..These results indicate that PLC-epsilon is a direct downstream effector for RhoA and that RhoA-dependent activation of PLC-epsilon depends on a unique insert within the catalytic core of the phospholipase...
  29. ncbi request reprint Agonist binding and Gq-stimulating activities of the purified human P2Y1 receptor
    Gary L Waldo
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7365, USA
    Mol Pharmacol 65:426-36. 2004
    ..These results illustrate that the binding and signaling properties of the human P2Y1-R can be studied with purified proteins under conditions that circumvent the complications that occur in vivo...
  30. ncbi request reprint Crystal structure of Rac1 bound to its effector phospholipase C-beta2
    Mark R Jezyk
    Department of Biochemistry and Biophysics The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Nat Struct Mol Biol 13:1135-40. 2006
    ....
  31. pmc Gi-dependent cell signaling responses of the human P2Y14 receptor in model cell systems
    Ingrid P Fricks
    Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599, USA
    J Pharmacol Exp Ther 330:162-8. 2009
    ..This work also identifies two stable P2Y(14)-R-expressing cell lines and differentiated HL-60 cells as model systems for the study of P2Y(14)-R-dependent signal transduction...
  32. pmc UDP is a competitive antagonist at the human P2Y14 receptor
    Ingrid P Fricks
    Department of Pharmacology, University of North Carolina, CB 7365 Mary Ellen Jones Bldg, Chapel Hill, NC 27599 7365, USA
    J Pharmacol Exp Ther 325:588-94. 2008
    ..35 muM) at the rat P2Y(14)-R. These results identify the first competitive antagonist of the P2Y(14)-R and demonstrate pharmacological differences between receptor orthologs...
  33. pmc Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform
    Jiyoung Y Cha
    Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599 7295, USA
    J Biol Chem 284:6227-40. 2009
    ..Our data support a dual mechanism where deletion of the 770YXXL773 motif promotes FGFR2 IIIb C3 transforming activity by causing aberrant receptor recycling and stability and persistent FRS2-dependent signaling...
  34. ncbi request reprint Quantitation of the P2Y(1) receptor with a high affinity radiolabeled antagonist
    Gary L Waldo
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Mol Pharmacol 62:1249-57. 2002
    ..Taken together, these results indicate that [(3)H]MRS2279 is the first broadly applicable antagonist radioligand for a P2Y receptor...
  35. ncbi request reprint Direct activation of purified phospholipase C epsilon by RhoA studied in reconstituted phospholipid vesicles
    Jason P Seifert
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, USA
    Methods Enzymol 406:260-71. 2006
    ..The capacity of GTPgammaS-bound RhoA to stimulate the phospholipase activity of PLC-epsilon is assessed by reconstitution of the RhoA in mixed-detergent phospholipid micelles containing PtdIns(4,5)P2 substrate...
  36. pmc Agonist versus antagonist action of ATP at the P2Y4 receptor is determined by the second extracellular loop
    Christopher L Herold
    Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599 7365, USA
    J Biol Chem 279:11456-64. 2004
    ..Taken together, these results suggest that the second extracellular loop and the NH(2) terminus form a functional motif that plays a key role in determining whether ATP functions as an agonist or antagonist at mammalian P2Y(4) receptors...
  37. ncbi request reprint Purification and in vitro functional analysis of R7 subfamily RGS proteins in complex with Gbeta5
    Shelley B Hooks
    Department of Pharmacology, University of North Carolina, Chapel Hill 27599, USA
    Methods Enzymol 390:163-77. 2004
    ..The ability of the heterodimers to accelerate the intrinsic GTPase activity of Galpha subunits was assessed in steady-state GTPase assays performed on proteoliposomes consisting of phospholipids, purified G proteins, and purified GPCRs...
  38. ncbi request reprint Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules
    Eduardo R Lazarowski
    Department of Pharmacology, University of North Carolina School of Medicine, CB 7365, Chapel Hill, NC 27599, USA
    Mol Pharmacol 64:785-95. 2003
  39. ncbi request reprint Polarized expression of human P2Y receptors in epithelial cells from kidney, lung, and colon
    Samuel C Wolff
    Department of Pharmacology, The University of North Carolina Chapel Hill, 1027 Mary Ellen Jones Bldg, CB 7365, Chapel Hill, NC 27599, USA
    Am J Physiol Cell Physiol 288:C624-32. 2005
    ..These experiments highlight the highly polarized expression of P2Y receptors in epithelial cells...
  40. pmc Structure of Galpha(i1) bound to a GDP-selective peptide provides insight into guanine nucleotide exchange
    Christopher A Johnston
    Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Structure 13:1069-80. 2005
    ..Our results cast light onto a potential mechanism by which Galpha subunits adopt a conformation suitable for nucleotide exchange...
  41. ncbi request reprint Release of cellular UDP-glucose as a potential extracellular signaling molecule
    Eduardo R Lazarowski
    Department of Medicine, Cystic Fibrosis Center, University of North Carolina School of Medicine, Chapel Hill 27599, USA
    Mol Pharmacol 63:1190-7. 2003
    ..Because cellular UDP-glucose is concentrated in the lumen of the endoplasmic reticulum, we speculate that UDP-glucose release may occur as a result of vesicle transport during trafficking of glycoproteins to the plasma membrane...
  42. pmc Activation of human phospholipase C-eta2 by Gbetagamma
    Yixing Zhou
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Biochemistry 47:4410-7. 2008
    ..Taken together, these studies illustrate that PLC-eta2 is a direct downstream effector of Gbetagamma and, therefore, of receptor-activated heterotrimeric G proteins...
  43. pmc Crystal structure of the multifunctional Gbeta5-RGS9 complex
    Matthew L Cheever
    Department of Pharmacology, University of North Carolina School of Medicine, Campus Box 7365, Chapel Hill, North Carolina 27599 7365, USA
    Nat Struct Mol Biol 15:155-62. 2008
    ..This structure reveals a canonical RGS domain that is functionally integrated within a molecular complex that is poised for integration of multiple steps during G-protein activation and deactivation...
  44. ncbi request reprint Requirement of Cys399 for processing of the human ecto-ATPase (NTPDase2) and its implications for determination of the activities of splice variants of the enzyme
    Jesús Mateo
    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7365, USA
    J Biol Chem 278:39960-8. 2003
    ....
  45. ncbi request reprint C(8) substituted 1-azabicyclo[3.3.1]non-3-enes and C(8) substituted 1-azabicyclo[3.3.1]nonan-4-ones: novel muscarinic receptor antagonists
    Myoung Goo Kim
    Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7360, USA
    J Med Chem 46:2216-26. 2003
    ..Compound 3 serves as a novel lead compound for further drug development...
  46. pmc Antiaggregatory activity in human platelets of potent antagonists of the P2Y 1 receptor
    Marco Cattaneo
    Hematology and Thrombosis Unit, Ospedale San Paolo, DMCO University of Milan, Milan, Italy
    Biochem Pharmacol 68:1995-2002. 2004
    ..Thus, all three of the bisphosphate derivatives are highly selective antagonists of the platelet P2Y(1) receptor, and MRS2500 is the most potent such antagonist yet reported...
  47. pmc 2-Substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane ring system locked in a northern conformation: enhanced potency as P2Y1 receptor antagonists
    Hak Sung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 0810, USA
    J Med Chem 46:4974-87. 2003
    ..An enzymatic method of synthesis of the 3',5'-bisphosphate from the corresponding 3'-monophosphate, suitable for the preparation of a radiophosphorylated analogue, was explored...
  48. ncbi request reprint Adenine nucleotide analogues locked in a Northern methanocarba conformation: enhanced stability and potency as P2Y(1) receptor agonists
    R Gnana Ravi
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases NIH, Building 8A, Room B1A 17, Bethesda, MD 20892 0810, USA
    J Med Chem 45:2090-100. 2002
    ..This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of the (N)-conformation, which greatly enhanced potency at P2Y(1) receptors...
  49. ncbi request reprint Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors
    Hak Sung Kim
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    J Med Chem 45:208-18. 2002
    ..Our results suggest that new nucleotide agonists may be designed on the basis of the (N) conformation that favors selectivity for P2Y1, P2Y2, P2Y4, and P2Y11 receptors...
  50. ncbi request reprint UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors
    Mingyan Hou
    Division of Experimental Vascular Research, Department of Medicine, University Hospital, SE 221 85 Lund, Sweden
    Am J Physiol Heart Circ Physiol 282:H784-92. 2002
    ..The results demonstrate that UDP stimulates mitogenesis through activation of P2Y(6) receptors and that the receptor is regulated by factors important in the development of vascular disease...
  51. pmc Nucleotide analogues containing 2-oxa-bicyclo[2.2.1]heptane and l-alpha-threofuranosyl ring systems: interactions with P2Y receptors
    Michihiro Ohno
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases NIH DHHS, Bethesda, MD 20892 0810, USA
    Bioorg Med Chem 12:5619-30. 2004
    ..9 microM) versus P2Y(4) receptors. The P2Y(1) receptor binding modes, including rotational angles, were estimated using molecular modeling and receptor docking...
  52. ncbi request reprint P2Y1 antagonists: combining receptor-based modeling and QSAR for a quantitative prediction of the biological activity based on consensus scoring
    Stefano Costanzi
    Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA
    J Med Chem 50:3229-41. 2007
    ..LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set...
  53. pmc Human P2Y(6) receptor: molecular modeling leads to the rational design of a novel agonist based on a unique conformational preference
    Stefano Costanzi
    NIDDK, National Institutes of Health, DHHS, Bethesda, Maryland 20892 USA
    J Med Chem 48:8108-11. 2005
    ..MD results also suggested a conformational change of the second extracellular loop consequent to agonist binding...
  54. ncbi request reprint Structure activity and molecular modeling analyses of ribose- and base-modified uridine 5'-triphosphate analogues at the human P2Y2 and P2Y4 receptors
    Kenneth A Jacobson
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem Pharmacol 71:540-9. 2006
    ....
  55. pmc Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists
    Hyojin Ko
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892 0810, USA
    Bioorg Med Chem 16:6319-32. 2008
    ....
  56. pmc Molecular modeling of the human P2Y2 receptor and design of a selective agonist, 2'-amino-2'-deoxy-2-thiouridine 5'-triphosphate
    Andrei A Ivanov
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 50:1166-76. 2007
    ..This detailed view of P2Y2 receptor recognition suggests mutations for model validation...
  57. pmc Structure-activity relationship of uridine 5'-diphosphoglucose analogues as agonists of the human P2Y14 receptor
    Hyojin Ko
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 50:2030-9. 2007
    ..The hexose moiety of UDPG interacts with multiple H-bonding and charged residues and provides a fertile region for agonist modification...
  58. pmc Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor
    Pedro Besada
    Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 49:5532-43. 2006
    ..These results provide a better understanding of molecular recognition at the P2Y6 receptor and will be helpful in designing selective and potent P2Y6 receptor ligands...

Research Grants25

  1. REGULATION OF PHOSPHOLIPASE C
    T Harden; Fiscal Year: 2002
    ..Completion of the work described in this proposal should considerably extend knowledge of the identify, specificity, and mechanism of interaction of the component proteins of the receptor-regulated inositol lipid signalling pathway. ..
  2. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2004
    ..abstract_text> ..
  3. G protein signal integration by multifunctional proteins
    T Harden; Fiscal Year: 2006
    ..abstract_text> ..
  4. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2007
    ....
  5. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2009
    ..We anticipate that furthering the basic understanding of other receptors in this group of important signaling proteins will lead to similarly important therapeutic agents. ..
  6. P2Y-PURINERGIC RECEPTORS
    T Kendall Harden; Fiscal Year: 2010
    ..We anticipate that furthering the basic understanding of other receptors in this group of important signaling proteins will lead to similarly important therapeutic agents. ..
  7. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2000
    ....
  8. MUSCARINIC RECEPTOR SUBTYPES ON CULTURED CELLS
    T Harden; Fiscal Year: 1991
    ..Rational therapy of a number of pathophysiological conditions, e.g. Alzheimer's disease, can ultimately benefit from this knowledge...
  9. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 1993
    ....
  10. P2Y-PURINERGIC RECEPTORS
    T Harden; Fiscal Year: 2009
    ..We anticipate that furthering the basic understanding of other receptors in this group of important signaling proteins will lead to similarly important therapeutic agents. ..