Andrew Tinker

Summary

Affiliation: University College London
Country: UK

Publications

  1. ncbi request reprint The molecular composition of K(ATP) channels in human pulmonary artery smooth muscle cells and their modulation by growth
    Yi Cui
    Centre for Clinical Pharmacology, Department of Medicine, Rayne Institute, University College London, London, United Kingdom
    Am J Respir Cell Mol Biol 26:135-43. 2002
  2. pmc Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature
    Alison Morrissey
    Pediatric Cardiology, NYU School of Medicine, New York, USA
    BMC Physiol 5:1. 2005
  3. pmc Monitoring changes in membrane phosphatidylinositol 4,5-bisphosphate in living cells using a domain from the transcription factor tubby
    Kathryn V Quinn
    BHF Laboratories and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
    J Physiol 586:2855-71. 2008
  4. ncbi request reprint The selective interactions and functions of regulators of G-protein signalling
    Andrew Tinker
    BHF Laboratories and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
    Semin Cell Dev Biol 17:377-82. 2006
  5. pmc Mechanisms of disease pathogenesis in long QT syndrome type 5
    Stephen C Harmer
    Department of Medicine, University College London, London, WC1E 6JJ, UK
    Am J Physiol Cell Physiol 298:C263-73. 2010
  6. pmc HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes
    Muriel Nobles
    Department of Medicine, BHF Laboratories, University College London, The Rayne Institute, 5 University Street, London, WC1E 6JJ, UK
    Pflugers Arch 460:99-108. 2010
  7. doi request reprint Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits
    Tabasum Farzaneh
    BHF Laboratories, Department of Medicine, The Rayne Institute, University College London, Room 107, 5 University Street, London WC1E 6JJ, UK
    Cardiovasc Res 79:621-31. 2008
  8. pmc Characterization of a binding site for anionic phospholipids on KCNQ1
    Alison M Thomas
    Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, United Kingdom
    J Biol Chem 286:2088-100. 2011
  9. pmc Absence of the inhibitory G-protein Galphai2 predisposes to ventricular cardiac arrhythmia
    Zia Zuberi
    Department of Medicine and Hatter Cardiovascular Institute, University College London, 5 University Street, London, England, UK
    Circ Arrhythm Electrophysiol 3:391-400. 2010
  10. ncbi request reprint PIP(2)-dependent inhibition of M-type (Kv7.2/7.3) potassium channels: direct on-line assessment of PIP(2) depletion by Gq-coupled receptors in single living neurons
    Simon Hughes
    Department of Pharmacology, University College London, London, WC1E 6BT, UK
    Pflugers Arch 455:115-24. 2007

Collaborators

Detail Information

Publications46

  1. ncbi request reprint The molecular composition of K(ATP) channels in human pulmonary artery smooth muscle cells and their modulation by growth
    Yi Cui
    Centre for Clinical Pharmacology, Department of Medicine, Rayne Institute, University College London, London, United Kingdom
    Am J Respir Cell Mol Biol 26:135-43. 2002
    ....
  2. pmc Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature
    Alison Morrissey
    Pediatric Cardiology, NYU School of Medicine, New York, USA
    BMC Physiol 5:1. 2005
    ..2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits) is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart...
  3. pmc Monitoring changes in membrane phosphatidylinositol 4,5-bisphosphate in living cells using a domain from the transcription factor tubby
    Kathryn V Quinn
    BHF Laboratories and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
    J Physiol 586:2855-71. 2008
    ..This probe may be valuable in examining changes in PtdIns(4,5)P(2) distinct from those of IP(3) in intact cells in a variety of physiological settings...
  4. ncbi request reprint The selective interactions and functions of regulators of G-protein signalling
    Andrew Tinker
    BHF Laboratories and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
    Semin Cell Dev Biol 17:377-82. 2006
    ..I discuss the molecular mechanisms by which these phenomena might be explained including specific interactions between the RGS and G-protein coupled receptor, G-protein and effector...
  5. pmc Mechanisms of disease pathogenesis in long QT syndrome type 5
    Stephen C Harmer
    Department of Medicine, University College London, London, WC1E 6JJ, UK
    Am J Physiol Cell Physiol 298:C263-73. 2010
    ..In conclusion, we identify the disease mechanisms for each mutation and reveal that T58P/L59P causes disease through a novel mechanism that involves defective I(Ks) complex assembly...
  6. pmc HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes
    Muriel Nobles
    Department of Medicine, BHF Laboratories, University College London, The Rayne Institute, 5 University Street, London, WC1E 6JJ, UK
    Pflugers Arch 460:99-108. 2010
    ..Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch...
  7. doi request reprint Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits
    Tabasum Farzaneh
    BHF Laboratories, Department of Medicine, The Rayne Institute, University College London, Room 107, 5 University Street, London WC1E 6JJ, UK
    Cardiovasc Res 79:621-31. 2008
    ..2 containing complexes, such as those present in cardiac myocytes. Thus, we investigated differences in the mechanism of metabolic regulation of Kir6.1 and Kir6.2 containing K(ATP) channels...
  8. pmc Characterization of a binding site for anionic phospholipids on KCNQ1
    Alison M Thomas
    Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, United Kingdom
    J Biol Chem 286:2088-100. 2011
    ..In conclusion, we use a combined biochemical and functional approach to identify a cluster of basic residues important for the binding and action of anionic phospholipids on the KCNQ1/KCNE1 complex...
  9. pmc Absence of the inhibitory G-protein Galphai2 predisposes to ventricular cardiac arrhythmia
    Zia Zuberi
    Department of Medicine and Hatter Cardiovascular Institute, University College London, 5 University Street, London, England, UK
    Circ Arrhythm Electrophysiol 3:391-400. 2010
    ..We explored the role that inhibitory heterotrimeric G-proteins play in ventricular arrhythmia...
  10. ncbi request reprint PIP(2)-dependent inhibition of M-type (Kv7.2/7.3) potassium channels: direct on-line assessment of PIP(2) depletion by Gq-coupled receptors in single living neurons
    Simon Hughes
    Department of Pharmacology, University College London, London, WC1E 6BT, UK
    Pflugers Arch 455:115-24. 2007
    ....
  11. ncbi request reprint The cytoplasmic C-terminus of the sulfonylurea receptor is important for KATP channel function but is not key for complex assembly or trafficking
    Jonathan P Giblin
    Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, UK
    Eur J Biochem 269:5303-13. 2002
    ..Our data show that deletions of the C-terminal most cytoplasmic domain of SUR1, can result in functional channels at the plasma membrane in mammalian cells that have an abnormal response to physiological and pharmacological agents...
  12. pmc Different molecular sites of action for the KATP channel inhibitors, PNU-99963 and PNU-37883A
    Yi Cui
    Centre for Clinical Pharmacology, BHF Laboratories, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, U K
    Br J Pharmacol 139:122-8. 2003
    ..While PNU-99963 potently inhibits all the four cloned K(ATP) channels, PNU-37883A has a degree of selectivity towards both smooth muscle K(ATP) channels, but could not discriminate between them...
  13. pmc Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells
    Muriel Nobles
    British Heart Foundation Laboratories and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, United Kingdom
    Proc Natl Acad Sci U S A 102:18706-11. 2005
    ..Our work suggests that GPCR dimers and the G protein heterotrimer are present at the cell membrane in the resting state in a pentameric complex...
  14. ncbi request reprint PKC-delta sensitizes Kir3.1/3.2 channels to changes in membrane phospholipid levels after M3 receptor activation in HEK-293 cells
    Sean G Brown
    Dept of Medicine, University College of London, London WC1E 6JJ, UK
    Am J Physiol Cell Physiol 289:C543-56. 2005
    ..Thus Kir3.1/3.2 channels are sensitive to changes in membrane phospholipid levels but this is contingent on the activity of PKC-delta after M(3) receptor activation in HEK-293 cells...
  15. ncbi request reprint Complex ABCC8 DNA variations in congenital hyperinsulinism: lessons from functional studies
    Morris Muzyamba
    BHF Laboratories and Department of Medicine, University College London, London, UK
    Clin Endocrinol (Oxf) 67:115-24. 2007
    ..2, respectively, are the commonest cause of CHI. We investigated whether the possession of two DNA variants leading to coding changes in a single allele of ABCC8 can affect the potential mechanism of disease pathogenesis...
  16. pmc A basic residue in the proximal C-terminus is necessary for efficient activation of the M-channel subunit Kv7.2 by PI(4,5)P₂
    Vsevolod Telezhkin
    Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK
    Pflugers Arch 465:945-53. 2013
    ..2) might play a major role in the activation of all members of the Kv7 channel family by PI(4,5)P2. ..
  17. ncbi request reprint Do anionic phospholipids serve as cofactors or second messengers for the regulation of activity of cloned ATP-sensitive K+ channels?
    Kathryn V Quinn
    BHF Laboratories and Department of Medicine, University College London, 5 University St, London WC1E 6JJ, UK
    Circ Res 93:646-55. 2003
    ..In this case, phosphatidylinositol 4,5-diphosphate and related species have the potential to act as second messengers in signaling. Thus, Kir6.1 and Kir6.2 are regulated by distinct inhibitory mechanisms...
  18. ncbi request reprint A novel strategy to engineer functional fluorescent inhibitory G-protein alpha subunits
    Joanne L Leaney
    BHF Laboratories, Room 420, 4th Floor, and Centre for Clinical Pharmacology, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, United Kingdom
    J Biol Chem 277:28803-9. 2002
    ..Overexpression of tagged G(i3)alpha and G(oA)alpha alpha subunits reduced receptor-mediated and forskolin-induced cAMP mobilization...
  19. pmc Agonist unbinding from receptor dictates the nature of deactivation kinetics of G protein-gated K+ channels
    Amy Benians
    Department of Medicine, Centre for Clinical Pharmacology and British Heart Foundation Laboratories, University College London, Room 420, 4th Floor, 5 University Street, United Kingdom
    Proc Natl Acad Sci U S A 100:6239-44. 2003
    ..G protein isoform and interaction with G protein-signaling proteins play a significant role with this group of GPCRs...
  20. ncbi request reprint Abnormal KCNQ1 trafficking influences disease pathogenesis in hereditary long QT syndromes (LQT1)
    Andrew J Wilson
    BHF Laboratories and Department of Medicine, University College London, 5 University Street, London, WC1E 6JJ, UK
    Cardiovasc Res 67:476-86. 2005
    ..In this study we investigated the role that abnormal KCNQ1 trafficking has in the pathogenesis of the hereditary long QT syndrome (LQT1)...
  21. ncbi request reprint Regulators of G-protein signaling form a quaternary complex with the agonist, receptor, and G-protein. A novel explanation for the acceleration of signaling activation kinetics
    Amy Benians
    BHF Laboratories and Department of Medicine, University College London, Room 420, 4th Floor, 5 University Street, London WC1E 6JJ, United Kingdom
    J Biol Chem 280:13383-94. 2005
    ..Thus we propose a novel model for the action of RGS proteins in the G-protein cycle in which the RGS protein appears to enhance the "kinetic efficacy" of the ternary complex, by direct association with the G-protein alpha subunit...
  22. ncbi request reprint Multisite phosphorylation mechanism for protein kinase A activation of the smooth muscle ATP-sensitive K+ channel
    Kathryn V Quinn
    British Heart Foundation Laboratories and the Department of Medicine, University College London, UK
    Circ Res 94:1359-66. 2004
    ..1 (S385) and two sites in SUR2B (T633 and S1465) using a combination of biochemical and functional assays. Our work supports a model in which multiple sites in the channel complex have to be phosphorylated before activation occurs...
  23. pmc Do caveolae have a role in the fidelity and dynamics of receptor activation of G-protein-gated inwardly rectifying potassium channels?
    Sarah Schwarzer
    Department of Medicine, BHF Laboratories, The Rayne Institute, University College London, London WC1E 6JJ, United Kingdom
    J Biol Chem 285:27817-26. 2010
    ..The presence of G(s)alpha solely in caveolae may account for signaling selectivity between G(i/o) and G(s)-coupled receptors...
  24. ncbi request reprint The dynamics of formation and action of the ternary complex revealed in living cells using a G-protein-gated K+ channel as a biosensor
    Amy Benians
    Centre for Clinical Pharmacology, The BHF Laboratories, Department of Medicine, University College London, United Kingdom
    J Biol Chem 278:10851-8. 2003
    ..Our studies indicate that the combination of agonist, GPCR, and G-protein isoform uniquely specify the behavior of these channels and thus support the importance of the whole ternary complex at a kinetic level...
  25. ncbi request reprint Rapid desensitization of G protein-gated inwardly rectifying K(+) currents is determined by G protein cycle
    Joanne L Leaney
    Departmentt of Medicine, University College London, London WC1E 6JJ, UK
    Am J Physiol Cell Physiol 287:C182-91. 2004
    ..Together our data suggest that fast desensitization of GIRK currents is accounted for by the fundamental properties of the G protein cycle...
  26. pmc Functional expression of inward rectifier potassium channels in cultured human pulmonary smooth muscle cells: evidence for a major role of Kir2.4 subunits
    Brian P Tennant
    Department of Medicine, BHF Laboratories, Rayne Institute, University College London, 5 University Street, London, WC1E 6JF, United Kingdom
    J Membr Biol 213:19-29. 2006
    ..3. We demonstrate that cultured HPASM cells express K(IR) channels and suggest both Kir2.1 and Kir2.4 subunits contribute to these channels, although the whole-cell current characteristics described share more similarity with Kir2.4...
  27. ncbi request reprint Differential phosphoinositide binding to components of the G protein-gated K+ channel
    Alison M Thomas
    Department of Medicine and BHF Laboratories, University College London, 5 University Street, London, WC1E 6JJ, United Kingdom
    J Membr Biol 211:43-53. 2006
    ..The differential binding affinity has functional consequences as the inhibition of homomeric Kir3.1, occurring after M3 receptor activation, recovers over minutes while homomeric Kir3.2 does not...
  28. pmc The role of inhibitory heterotrimeric G proteins in the control of in vivo heart rate dynamics
    Zia Zuberi
    British Heart Foundation, Laboratories and Department of Medicine, University College London, 5 University St, London, WC1E 6JJ, UK
    Am J Physiol Regul Integr Comp Physiol 295:R1822-30. 2008
    ..In contrast, Galphai1 and Galphai3 do not appear to be essential for parasympathetic responses in vivo...
  29. doi request reprint Determination of phosphoinositide binding to K(+) channel subunits using a protein-lipid overlay assay
    Alison M Thomas
    Department of Medicine, University College London, UK
    Methods Mol Biol 491:103-11. 2008
    ..0 family, where only the cytoplasmic C-terminal Kir3.1 domain and the N- and C-terminal domains of Kir3.4 have the ability to bind to anionic phospholipids...
  30. doi request reprint The intracellular localization and function of the ATP-sensitive K+ channel subunit Kir6.1
    Keat Eng Ng
    Deparment of Medicine, The Rayne Institute, University College London, Room 107, University Street, London, WC1E 6JF, UK
    J Membr Biol 234:137-47. 2010
    ..This study suggests that Kir6.1 is located in the endoplasmic reticulum and plays a role in modifying Ca2+ release from intracellular stores...
  31. doi request reprint In vitro and in vivo cardiomyogenic differentiation of amniotic fluid stem cells
    Sveva Bollini
    Stem Cell Processing Laboratory Fondazione Città della Speranza, Venetian Institute of Molecular Medicine VIMM, University of Padua, Via G Orus, 2, 35129, Padua, Italy
    Stem Cell Rev 7:364-80. 2011
    ..rAFS cells have the in vitro propensity to acquire a cardiomyogenic phenotype and to preserve cardiac function, even if their potential may be limited by poor survival in an allogeneic setting...
  32. ncbi request reprint Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery
    Lucie H Clapp
    Centre for Clinical Pharmacology, Department of Medicine, University College London, Rayne Institute 4th Floor, 5 University Street, London W1C 6JJ, United Kingdom
    Am J Respir Cell Mol Biol 26:194-201. 2002
    ..Thus, PGI(2) analogs potently inhibit proliferation of human pulmonary artery, probably via a cAMP-dependent pathway, although cAMP elevation in itself is not a good predictor of antiproliferative potency...
  33. doi request reprint An efficient asymmetric synthesis of the potent beta-blocker ICI-118,551 allows the determination of enantiomer dependency on biological activity
    James R Baker
    Department of Chemistry, University College London, 20 Gordon St, London, UK
    Chem Commun (Camb) 46:3953-4. 2010
    ....
  34. doi request reprint Bromo- and thiomaleimides as a new class of thiol-mediated fluorescence 'turn-on' reagents
    Judith Youziel
    Department of Chemistry, University College London, 20 Gordon St, London, UK
    Org Biomol Chem 12:557-60. 2013
    ..These reagents thus offer opportunities in thiol sensing and intracellular reporting. ..
  35. doi request reprint Epistatic rescue of Nkx2.5 adult cardiac conduction disease phenotypes by prospero-related homeobox protein 1 and HDAC3
    Catherine A Risebro
    Institute of Child Health, University College London, UK
    Circ Res 111:e19-31. 2012
    ..5 in the mouse phenocopies human conduction disease pathology yet the phenotypes, described in both mouse and man, are highly pleiotropic, implicit of unknown modifiers and/or factors acting in epistasis with Nkx2.5/NKX2.5...
  36. pmc IP receptor-dependent activation of PPARgamma by stable prostacyclin analogues
    Emilia Falcetti
    BHF Laboratories, Department of Medicine, Rayne Building, University College London, London WC1E 6JF, UK
    Biochem Biophys Res Commun 360:821-7. 2007
    ..We conclude that PPARgamma is activated through the IP receptor via a cyclic AMP-independent mechanism and contributes to the anti-growth effects of prostacyclin analogues...
  37. pmc The design, synthesis and pharmacological characterization of novel β₂-adrenoceptor antagonists
    J Daniel Hothersall
    Department of Medicine, University College London, London, UK
    Br J Pharmacol 164:317-31. 2011
    ..Selective and potent antagonists for the β(2) -adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology...
  38. pmc In situ maleimide bridging of disulfides and a new approach to protein PEGylation
    Felix F Schumacher
    Department of Chemistry, University College London, 20 Gordon Street, London, WC1H OAJ, United Kingdom
    Bioconjug Chem 22:132-6. 2011
    ..This approach is then used to PEGylate the peptide hormone somatostatin and retention of biological activity is demonstrated...
  39. doi request reprint Phenformin has a direct inhibitory effect on the ATP-sensitive potassium channel
    Qadeer Aziz
    Department of Medicine, University College London, Rayne Institute, 5 University Street, London, WC1E 6JJ, United Kingdom
    Eur J Pharmacol 634:26-32. 2010
    ..0 subunit however the sulphonylurea receptor is able to significantly modulate the affinity. It is likely to block from the intracellular side of the channel in a manner analogous to that of PNU 37883A...
  40. pmc Regulation of M(Kv7.2/7.3) channels in neurons by PIP(2) and products of PIP(2) hydrolysis: significance for receptor-mediated inhibition
    David A Brown
    Department of Pharmacology, University College London, London, WC1E 6BT, UK
    J Physiol 582:917-25. 2007
    ..Thus, inhibition by bradykinin can use product (IP(3)/Ca(2)+)-dependent or substrate (PIP(2)) dependent mechanisms, depending on Ca(2)+ availability and PIP(2) synthesis rates...
  41. doi request reprint Regulation of mitochondrial structure and function by the F1Fo-ATPase inhibitor protein, IF1
    Michelangelo Campanella
    Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK
    Cell Metab 8:13-25. 2008
    ..Thus, IF(1) regulates mitochondrial function and structure under both physiological and pathological conditions...
  42. ncbi request reprint Assembly limits the pharmacological complexity of ATP-sensitive potassium channels
    Jonathan P Giblin
    Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, London WC1E 6JJ, United Kingdom
    J Biol Chem 277:13717-23. 2002
    ..This incompatibility limits the pharmacological complexity of K(ATP) channels that may be observed in native tissues...
  43. pmc NRP1 and NRP2 cooperate to regulate gangliogenesis, axon guidance and target innervation in the sympathetic nervous system
    Charlotte H Maden
    UCL Institute of Ophthalmology, University College London, UK
    Dev Biol 369:277-85. 2012
    ..We further show that abnormal sympathetic development in mice lacking NRP1 in the sympathetic lineage has functional consequences, as it causes sinus bradycardia, similar to mice lacking SEMA3A...
  44. ncbi request reprint K(+) channels in the heart: new insights and therapeutic implications
    Andrew Tinker
    BHF Laboratories and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK
    Expert Rev Clin Pharmacol 3:305-19. 2010
    ..Drugs targeting I(Kur) (K(v)1.5), and to a lesser extent I(KACh) (Kir3.1/3.4), are in various stages of development...
  45. ncbi request reprint Syntaxin-1A actions on sulfonylurea receptor 2A can block acidic pH-induced cardiac K(ATP) channel activation
    Youhou Kang
    Department of Medicine, University of Toronto, Toronto, Canada M5S 1A8
    J Biol Chem 281:19019-28. 2006
    ....
  46. pmc The large-conductance Ca2+-activated K+ channel is essential for innate immunity
    Jatinder Ahluwalia
    Department of Medicine University College London, Gower Street, London WC1E 6BT, UK
    Nature 427:853-8. 2004
    ..Remarkably, microbial killing and digestion were abolished when the BK(Ca) channel was blocked, revealing an essential and unexpected function for this K+ channel in the microbicidal process...