N M Hooper

Summary

Affiliation: University of Leeds
Country: UK

Publications

  1. pmc Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein
    David R Taylor
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 284:22590-600. 2009
  2. pmc Glypican-1 mediates both prion protein lipid raft association and disease isoform formation
    David R Taylor
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    PLoS Pathog 5:e1000666. 2009
  3. pmc Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor
    Christopher J Duff
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, U K
    Biochem J 419:577-84. 2009
  4. pmc Prion protein facilitates uptake of zinc into neuronal cells
    Nicole T Watt
    Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
    Nat Commun 3:1134. 2012
  5. pmc Prion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1
    Jo V Rushworth
    School of Molecular and Cellular Biology, Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom
    J Biol Chem 288:8935-51. 2013
  6. pmc Lipid Rafts: Linking Alzheimer's Amyloid-β Production, Aggregation, and Toxicity at Neuronal Membranes
    Jo V Rushworth
    Institute of Molecular and Cellular Biology, Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    Int J Alzheimers Dis 2011:603052. 2010
  7. pmc The role of zinc in Alzheimer's disease
    Nicole T Watt
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
    Int J Alzheimers Dis 2011:971021. 2010
  8. pmc Prion protein is decreased in Alzheimer's brain and inversely correlates with BACE1 activity, amyloid-β levels and Braak stage
    Isobel J Whitehouse
    School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
    PLoS ONE 8:e59554. 2013
  9. pmc Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain
    Victoria Lewis
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
    PLoS ONE 7:e31754. 2012
  10. pmc Neuronal zinc regulation and the prion protein
    Nicole T Watt
    School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    Prion 7:203-8. 2013

Collaborators

Detail Information

Publications103 found, 100 shown here

  1. pmc Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein
    David R Taylor
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 284:22590-600. 2009
    ..Collectively, these data indicate that although PrP(C) can be shed through the action of ADAM family members, modulation of PrP(C) or PrP(Sc) ectodomain shedding does not regulate prion conversion...
  2. pmc Glypican-1 mediates both prion protein lipid raft association and disease isoform formation
    David R Taylor
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    PLoS Pathog 5:e1000666. 2009
    ..These data indicate that glypican-1 is a novel cellular cofactor for prion conversion and we propose that it acts as a scaffold facilitating the interaction of PrP(C) and PrP(Sc) in lipid rafts...
  3. pmc Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor
    Christopher J Duff
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, U K
    Biochem J 419:577-84. 2009
    ..These data indicate that antibodies targeting PCSK9 can reverse the PCSK9-mediated modulation of cell-surface LDLRs...
  4. pmc Prion protein facilitates uptake of zinc into neuronal cells
    Nicole T Watt
    Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
    Nat Commun 3:1134. 2012
    ..These data suggest that alterations in the cellular prion protein-mediated zinc uptake may contribute to neurodegeneration in prion and other neurodegenerative diseases...
  5. pmc Prion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1
    Jo V Rushworth
    School of Molecular and Cellular Biology, Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom
    J Biol Chem 288:8935-51. 2013
    ....
  6. pmc Lipid Rafts: Linking Alzheimer's Amyloid-β Production, Aggregation, and Toxicity at Neuronal Membranes
    Jo V Rushworth
    Institute of Molecular and Cellular Biology, Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    Int J Alzheimers Dis 2011:603052. 2010
    ..The formation of these pathogenic lipid raft-based platforms may be critical for the toxic signalling mechanisms that underlie synaptic dysfunction and neuropathology in AD...
  7. pmc The role of zinc in Alzheimer's disease
    Nicole T Watt
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
    Int J Alzheimers Dis 2011:971021. 2010
    ..Thus, zinc dyshomeostasis may have a critical role to play in the pathogenesis of AD, and the chelation of zinc is a potential therapeutic approach...
  8. pmc Prion protein is decreased in Alzheimer's brain and inversely correlates with BACE1 activity, amyloid-β levels and Braak stage
    Isobel J Whitehouse
    School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
    PLoS ONE 8:e59554. 2013
    ..625). These data are consistent with a role for PrP(C) in regulating Aβ production and indicate that brain PrP(C) level may be important in influencing the onset and progression of sporadic AD...
  9. pmc Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain
    Victoria Lewis
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
    PLoS ONE 7:e31754. 2012
    ....
  10. pmc Neuronal zinc regulation and the prion protein
    Nicole T Watt
    School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    Prion 7:203-8. 2013
    ....
  11. pmc Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE
    Monika Rella
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    BMC Genomics 8:194. 2007
    ..Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals...
  12. ncbi request reprint Could inhibition of the proteasome cause mad cow disease?
    Nigel M Hooper
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    Trends Biotechnol 21:144-5. 2003
    ....
  13. ncbi request reprint Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein
    N M Hooper
    Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK
    Biochem Soc Trans 33:335-8. 2005
    ....
  14. ncbi request reprint Foreword: lipid rafts/biophysics, cell signalling, trafficking and processing
    Nigel M Hooper
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, UK
    Mol Membr Biol 23:1-3. 2006
  15. ncbi request reprint Prion disease: close encounters of the cellular kind
    Nigel M Hooper
    School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, Leeds, UK
    Curr Biol 12:R248-9. 2002
    ..Co-culture of prion-infected cells with uninfected target cells has recently been found to lead to rapid and efficient transmission of infectivity to the target cells by a process that is dependent on direct cell contact...
  16. doi request reprint Mechanism of the metal-mediated endocytosis of the prion protein
    Nigel M Hooper
    Faculty of Biological Sciences, Proteolysis Research Group, Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK
    Biochem Soc Trans 36:1272-6. 2008
    ..Zn(2+) also promotes the endocytosis of PrP(c), a phenomenon that is also dependent on the octapeptide repeats and requires LRP1...
  17. doi request reprint Glypican-1 facilitates prion conversion in lipid rafts
    Nigel M Hooper
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    J Neurochem 116:721-5. 2011
    ....
  18. ncbi request reprint The search for alpha-secretase and its potential as a therapeutic approach to Alzheimer s disease
    N M Hooper
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, UK
    Curr Med Chem 9:1107-19. 2002
    ....
  19. doi request reprint A new take on prions: preventing Alzheimer's disease
    Nigel M Hooper
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    Trends Biochem Sci 33:151-5. 2008
    ..New data indicate that the normal cellular form of the prion protein might have a crucial role in suppressing the production of the amyloid-beta peptide, the neurotoxic molecule involved in the pathogenesis of Alzheimer's disease...
  20. ncbi request reprint Proteases: a primer
    Nigel M Hooper
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U K
    Essays Biochem 38:1-8. 2002
    ..Protease activity can be regulated in vivo by endogenous inhibitors, by the activation of zymogens and by altering the rate of their synthesis and degradation...
  21. ncbi request reprint Determination of glycosyl-phosphatidylinositol membrane protein anchorage
    N M Hooper
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT
    Proteomics 1:748-55. 2001
    ..This detergent insolubility can be used to provide evidence for the presence of a GPI anchor on a protein and to isolate lipid rafts...
  22. ncbi request reprint Detergent-insoluble glycosphingolipid/cholesterol-rich membrane domains, lipid rafts and caveolae (review)
    N M Hooper
    School of Biochemistry and Molecular Biology, University of Leeds, UK
    Mol Membr Biol 16:145-56. 1999
    ....
  23. ncbi request reprint Glycosyl-phosphatidylinositol anchored membrane enzymes
    N M Hooper
    School of Biochemistry and Molecular Biology, University of Leeds, UK
    Clin Chim Acta 266:3-12. 1997
    ..Thus, a GPI anchor can confer additional properties on enzymes that may be important in their physiological and pathophysiological functioning...
  24. ncbi request reprint Protein processing mechanisms: from angiotensin-converting enzyme to Alzheimer's disease
    N M Hooper
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U K
    Biochem Soc Trans 28:441-6. 2000
    ....
  25. pmc Differential effects of glycosphingolipids on the detergent-insolubility of the glycosylphosphatidylinositol-anchored membrane dipeptidase
    E T Parkin
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    Biochem J 358:209-16. 2001
    ....
  26. pmc Roles of the juxtamembrane and extracellular domains of angiotensin-converting enzyme in ectodomain shedding
    S Pang
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    Biochem J 358:185-92. 2001
    ..These data are discussed in the context of two classes of secretases that differ in their requirements for recognition of substrate proteins...
  27. pmc Isolation and characterization of two distinct low-density, Triton-insoluble, complexes from porcine lung membranes
    E T Parkin
    Department of Biochemistry and Molecular Biology, University of Leeds, U K
    Biochem J 319:887-96. 1996
    ....
  28. ncbi request reprint Proteolytic fragmentation reveals the oligomeric and domain structure of porcine aminopeptidase A
    J R Hesp
    Department of Biochemistry and Molecular Biology, University of Leeds, U K
    Biochemistry 36:3000-7. 1997
    ....
  29. pmc Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism
    Gillian I Rice
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK
    Biochem J 383:45-51. 2004
    ..These kinetic data highlight that the flux of peptides through the RAS is complex, with the levels of ACE, ACE2 and NEP dictating whether vasoconstriction or vasodilation will predominate...
  30. ncbi request reprint Site-directed mutagenesis of conserved cysteine residues in porcine membrane dipeptidase. Cys 361 alone is involved in disulfide-linked dimerization
    S Keynan
    Department of Biochemistry and Molecular Biology, University of Leeds, U K
    Biochemistry 35:12511-7. 1996
    ..The expressed C361G mutant, unlike the wild type, is released from COS-1 cell membranes by trypsin and by an endogenous serine protease...
  31. ncbi request reprint Membrane-associated zinc peptidase families: comparing ACE and ACE2
    J L Guy
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds, LS2 9JT, UK
    Biochim Biophys Acta 1751:2-8. 2005
    ..As the complexity of this crucial pathway is unravelled, there is a growing interest in the therapeutic potential of agents that modulate the activity of ACE2...
  32. ncbi request reprint The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein
    Tobias M J Allinson
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, UK
    Eur J Biochem 271:2539-47. 2004
    ..These results indicate that neither ADAM10 nor TACE are involved in the shedding of ACE and that APMA, which activates a distinct ACE secretase, is the first pharmacological agent to distinguish between the shedding of ACE and APP...
  33. ncbi request reprint Structure-activity relationship of hydroxamate-based inhibitors on the secretases that cleave the amyloid precursor protein, angiotensin converting enzyme, CD23, and pro-tumor necrosis factor-alpha
    Edward T Parkin
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    Biochemistry 41:4972-81. 2002
    ..The compounds reported here will be useful in future studies aimed at identifying and validating candidate secretases...
  34. ncbi request reprint Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme
    G S Cottrell
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, The University of Leeds, Leeds, LS2 9JT United Kingdom
    Biochemistry 39:15121-8. 2000
    ..Neither Co(II) nor Zn(II) reactivated the metal-free enzyme. On the basis of these data we propose that human cytosolic AP-P is a single metal ion-dependent enzyme and that manganese is most likely the metal ion used in vivo...
  35. ncbi request reprint Reactive oxygen species-mediated beta-cleavage of the prion protein in the cellular response to oxidative stress
    Nicole T Watt
    Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 280:35914-21. 2005
    ..These data indicate that the beta-cleavage of PrP(C) is an early and critical event in the mechanism by which PrP protects cells against oxidative stress...
  36. ncbi request reprint Assigning functions to distinct regions of the N-terminus of the prion protein that are involved in its copper-stimulated, clathrin-dependent endocytosis
    David R Taylor
    Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK
    J Cell Sci 118:5141-53. 2005
    ..In addition, we have been able to assign distinct functions in the endocytic process to separate regions of the protein...
  37. ncbi request reprint Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cells
    Fiona J Warner
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 280:39353-62. 2005
    ..These studies suggest that both ACE2 and ACE are ectoenzymes that have distinct localization and secretion patterns that determine their role on the cell surface in kidney epithelium and in urine...
  38. ncbi request reprint Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat region
    W S Perera
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    Curr Biol 11:519-23. 2001
    ....
  39. ncbi request reprint Glycosylation and GPI anchorage of the prion protein
    N M Hooper
    School of Biochemistry and Microbiology, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    Adv Exp Med Biol 564:95-6. 2005
  40. ncbi request reprint Proteolytic mechanisms in amyloid-beta metabolism: therapeutic implications for Alzheimer's disease
    Emma R L C Vardy
    Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
    Trends Mol Med 11:464-72. 2005
    ....
  41. ncbi request reprint The prion protein and neuronal zinc homeostasis
    Nicole T Watt
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK LS2 9JT
    Trends Biochem Sci 28:406-10. 2003
    ..In prion disease, when the protein undergoes a conformational change to the infectious form, this function of PrP in zinc homeostasis might be compromised...
  42. ncbi request reprint Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependence
    Jodie L Guy
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom
    Biochemistry 42:13185-92. 2003
    ....
  43. pmc Molecular cloning and expression in COS-1 cells of pig kidney aminopeptidase P
    R J Hyde
    Department of Biochemistry and Molecular Biology, University of Leeds, U K
    Biochem J 319:197-201. 1996
    ..Sequence comparisons confirm that AP-P is a member of the proline peptidase family of hydrolytic enzymes and is unrelated in sequence to other brush-border membrane peptidases...
  44. ncbi request reprint The carboxyl terminus of Dictyostelium discoideum protein 1I encodes a functional glycosyl-phosphatidylinositol signal sequence
    B A Stevens
    School of Biochemistry and Molecular Biology, University of Leeds, Woodhouse Lane, LS2 9JT, Leeds, UK
    Biochim Biophys Acta 1511:317-29. 2001
    ..These parallel approaches show that the C-terminal signal sequence of 1I can direct the addition of a GPI anchor...
  45. ncbi request reprint The response of neurones and glial cells to elevated copper
    N T Watt
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK
    Brain Res Bull 55:219-24. 2001
    ..These data suggest that copper sequestration does not occur in neuronal cells exposed to elevated extracellular copper concentrations...
  46. ncbi request reprint Angiotensin-converting enzyme-2: a molecular and cellular perspective
    F J Warner
    School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom
    Cell Mol Life Sci 61:2704-13. 2004
    ....
  47. pmc Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein
    Edward T Parkin
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
    Proc Natl Acad Sci U S A 104:11062-7. 2007
    ..In conclusion, this is a mechanism by which the cellular production of the neurotoxic Abeta is regulated by PrP(C) and may have implications for both Alzheimer's and prion diseases...
  48. pmc The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion protein
    David R Taylor
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK
    Biochem J 402:17-23. 2007
    ..We show also that another LRP1 ligand that can cause neurodegenerative disease, the Alzheimer's amyloid precursor protein, does not modulate the endocytosis of PrP(C)...
  49. ncbi request reprint The prion protein and lipid rafts
    David R Taylor
    Proteolysis Research Group, Leeds Institute of Genetics, Health and Therapeutics, Faculty of Biological Sciences, University of Leeds, UK
    Mol Membr Biol 23:89-99. 2006
    ..Lipid rafts appear to be involved in the conformational conversion of PrP(C) to PrP(Sc), possibly by providing a favourable environment for this process to occur and enabling disease progression...
  50. ncbi request reprint N-glycans, not the GPI anchor, mediate the apical targeting of a naturally glycosylated, GPI-anchored protein in polarised epithelial cells
    Susan Pang
    School of Biochemistry and Microbiology, University of Leeds, LS2 9JT, UK
    J Cell Sci 117:5079-86. 2004
    ..These data indicate that it is the N-glycans, not the association of the GPI anchor with lipid rafts, which determine apical targeting of an endogenously N-glycosylated, GPI-anchored protein in polarised epithelial cells...
  51. pmc Characterization of the glycosyl-phosphatidylinositol-anchored human renal dipeptidase reveals that it is more extensively glycosylated than the pig enzyme
    N M Hooper
    Department of Biochemistry, University of Leeds, U K
    Biochem J 265:429-33. 1990
    ....
  52. ncbi request reprint The cloning and functional expression of human pancreatic aminopeptidase P
    G S Cottrell
    School of Biochemistry and Molecular Biology, University of Leeds, UK
    Biochem Soc Trans 26:S248. 1998
  53. ncbi request reprint Ectodomain shedding of cystinyl aminopeptidase from human placental membranes
    L D Ofner
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
    Placenta 23:65-70. 2002
    ..These results have implications for our understanding of the mechanism underlying the reduction in serum levels of CAP observed in certain pregnancy-related disorders, such as pre-eclampsia...
  54. ncbi request reprint Contamination of nuclear fractions with plasma membrane lipid rafts
    Yee How Say
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    Proteomics 7:1059-64. 2007
    ....
  55. ncbi request reprint Sphingomyelin chain length influences the distribution of GPI-anchored proteins in rafts in supported lipid bilayers
    Ashley E Garner
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    Mol Membr Biol 24:233-42. 2007
    ....
  56. ncbi request reprint The N-terminal region of the prion protein ectodomain contains a lipid raft targeting determinant
    Adrian R Walmsley
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 278:37241-8. 2003
    ..These data indicate that the N-terminal region of PrP acts as a cellular raft targeting determinant and that residues 23-90 of PrP represent the first proteinaceous raft targeting signal within the ectodomain of a GPI-anchored protein...
  57. ncbi request reprint ADAMs family members as amyloid precursor protein alpha-secretases
    Tobias M J Allinson
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, United Kingdom
    J Neurosci Res 74:342-52. 2003
    ....
  58. ncbi request reprint Reactive oxygen species (ROS)-mediated beta-cleavage of the prion protein in the mechanism of the cellular response to oxidative stress
    N T Watt
    Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK
    Biochem Soc Trans 33:1123-5. 2005
    ..These results suggest that beta-cleavage of PrP(C) is an initial consequence following exposure to ROS in the extracellular environment contributing to a pathway involved in antioxidant protection of neuronal cells...
  59. doi request reprint The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill
    Amy L Cilia La Corte
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    J Renin Angiotensin Aldosterone Syst 9:221-5. 2008
    ..Angiotensin-converting enzyme (ACE) and aminopeptidase P (AP-P) are key enzymes in these systems and are both involved in the degradation of the vasodilator bradykinin...
  60. ncbi request reprint Emerging and potential therapies for Alzheimer's disease
    Heledd H Griffiths
    University of Leeds, Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Leeds Institute of Genetics, Health and Therapeutics, Leeds LS2 9JT, UK
    Expert Opin Ther Targets 12:693-704. 2008
    ..The amyloid beta (Abeta) peptide is critical to the development of Alzheimer's disease (AD), the major neurodegenerative disease of the elderly for which there is currently no cure...
  61. ncbi request reprint The involvement of lipid rafts in Alzheimer's disease
    Joanna M Cordy
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, UK
    Mol Membr Biol 23:111-22. 2006
    ..Rafts may be involved in the aggregation of Ass and also in its clearance by amyloid-degrading enzymes such as plasmin or possibly neprilysin (NEP)...
  62. ncbi request reprint Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain
    Daniel W Lambert
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    FEBS Lett 582:385-90. 2008
    ..We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors...
  63. ncbi request reprint Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study
    Gillian I Rice
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT United Kingdom
    Hypertension 48:914-20. 2006
    ..ACE and NEP were associated with systolic and diastolic BP in univariate analyses; however, only ACE was independently associated with systolic and diastolic BP after accounting for covariates and shared childhood household...
  64. ncbi request reprint Role of lipid rafts in the processing of the pathogenic prion and Alzheimer's amyloid-beta proteins
    David R Taylor
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK
    Semin Cell Dev Biol 18:638-48. 2007
    ..Here, we discuss these findings and their implications for our understanding of these disease processes. In addition, the potential for rafts as sites for therapeutic intervention in prion diseases and Alzheimer's disease is considered...
  65. ncbi request reprint Emerging therapeutics for Alzheimer's disease
    Emma R L C Vardy
    University of Leeds, Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, Clarendon Way, Leeds LS2 9JT, UK
    Expert Rev Neurother 6:695-704. 2006
    ..Each of these will be considered, in detail, in terms of the variety of therapeutic approaches currently being investigated and mechanisms that may prove amenable to intervention in the future...
  66. ncbi request reprint The Caenorhabditis elegans orthologue of mammalian puromycin-sensitive aminopeptidase has roles in embryogenesis and reproduction
    Darren R Brooks
    Molecular and Cellular Biosciences, Faculty of Biological Sciences, University of Leeds, Miall Bldg, Leeds, West Yorkshire LS2 9JT, United Kingdom
    J Biol Chem 278:42795-801. 2003
    ..We conclude that pam-1 encodes an aminopeptidase that clusters phylogenetically with the PSAs, despite attenuated sensitivity toward puromycin, and that it functions in embryo development and reproduction of the nematode...
  67. ncbi request reprint ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors
    Anthony J Turner
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, UK
    Can J Physiol Pharmacol 80:346-53. 2002
    ..Thus, the ACEH protein may have evolved as a chimera of a single ACE-like domain and a collectrin domain. The collectrin domain may regulate tissue response to injury whereas the catalytic domain is involved in peptide processing events...
  68. ncbi request reprint The ectodomain shedding of angiotensin-converting enzyme is independent of its localisation in lipid rafts
    Edward T Parkin
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    J Cell Sci 116:3079-87. 2003
    ..These data clearly show that the protein kinase C-stimulated shedding of ACE does not require the transmembrane or cytosolic regions of the protein, and that sequestration in lipid rafts does not regulate the shedding of the protein...
  69. ncbi request reprint Tethering the N-terminus of the prion protein compromises the cellular response to oxidative stress
    Fanning Zeng
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK
    J Neurochem 84:480-90. 2003
    ....
  70. pmc Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein
    Joanna M Cordy
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    Proc Natl Acad Sci U S A 100:11735-40. 2003
    ..Changes in the local membrane environment during aging may facilitate the cosegregation of APP and BACE leading to increased beta-amyloid production...
  71. ncbi request reprint Muscarine enhances soluble amyloid precursor protein secretion in human neuroblastoma SH-SY5Y by a pathway dependent on protein kinase C(alpha), src-tyrosine kinase and extracellular signal-regulated kinase but not phospholipase C
    Rosa Maria Canet-Aviles
    Academic Unit of Cardiovascular Medicine, University of Leeds, Leeds, UK
    Brain Res Mol Brain Res 102:62-72. 2002
    ....
  72. ncbi request reprint Dual mechanisms for shedding of the cellular prion protein
    Edward T Parkin
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 279:11170-8. 2004
    ..Collectively, our data indicate that shedding of PrP(C) can occur via both secretase-like proteolytic cleavage of the protein and phospholipase cleavage of the GPI anchor moiety...
  73. ncbi request reprint ACE2: from vasopeptidase to SARS virus receptor
    Anthony J Turner
    School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK
    Trends Pharmacol Sci 25:291-4. 2004
    ..Unexpectedly, ACE2 also serves as the cellular entry point for the severe acute respiratory syndrome (SARS) virus and the enzyme is therefore a prime target for pharmacological intervention on several disease fronts...
  74. ncbi request reprint The angiotensin-converting enzyme gene family: genomics and pharmacology
    Anthony J Turner
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, Leeds, UK
    Trends Pharmacol Sci 23:177-83. 2002
    ..The gene that encodes collectrin, a homologue of ACEH, is upregulated in response to renal injury. Collectrin lacks a catalytic domain, which indicates that there is more to ACE-like function than simple peptide hydrolysis...
  75. ncbi request reprint Secretase-mediated cell surface shedding of the angiotensin-converting enzyme
    Edward T Parkin
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
    Protein Pept Lett 11:423-32. 2004
    ..The secretase cleavage site in somatic ACE has been mapped to Arg-1203/Ser-1204, 24 residues proximal to the membrane-anchoring domain and the ADAM ('a disintegrin and metalloprotease') family of proteins may be involved in ACE shedding...
  76. doi request reprint Ligand-stimulated VEGFR2 signaling is regulated by co-ordinated trafficking and proteolysis
    Alexander F Bruns
    Endothelial Cell Biology Unit, Institute of Molecular and Cellular Biology, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK
    Traffic 11:161-74. 2010
    ..Thus, removal of the VEGFR2 carboxyl terminus linked to phosphorylation, ubiquitination and trafficking is necessary for VEGF-stimulated endothelial signaling and cell migration...
  77. ncbi request reprint Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)
    Daniel W Lambert
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Biol Chem 280:30113-9. 2005
    ..The identification of ADAM17 as the protease responsible for ACE2 shedding may provide new insight into the physiological roles of ACE2...
  78. ncbi request reprint Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesis
    Jodie L Guy
    School of Biochemistry and Microbiology, University of Leeds, UK
    FEBS J 272:3512-20. 2005
    ..This is the first study to address the differences that exist between ACE2 and ACE at the molecular level. The results can be applied to future studies aimed at unravelling the role of ACE2, relative to ACE, in vivo...
  79. ncbi request reprint A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase
    S R Tipnis
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds, United Kingdom
    J Biol Chem 275:33238-43. 2000
    ..4 kilobase pairs and is most highly expressed in testis, kidney, and heart. This is the first report of a mammalian homolog of ACE and has implications for our understanding of cardiovascular and renal function...
  80. doi request reprint alpha-cleavage of the prion protein occurs in a late compartment of the secretory pathway and is independent of lipid rafts
    Adrian R Walmsley
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS29JT, UK
    Mol Cell Neurosci 40:242-8. 2009
    ..Our data thus demonstrate that the alpha-cleavage of PrP(C) occurs predominantly in a raft-independent manner in a late compartment of the secretory pathway...
  81. ncbi request reprint Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line, SH-SY5Y
    Leigh D Plant
    School of Biomedical Sciences, University of Leeds, Leeds, UK
    Neuroreport 13:1553-6. 2002
    ....
  82. pmc Visualization of detergent solubilization of membranes: implications for the isolation of rafts
    Ashley E Garner
    Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    Biophys J 94:1326-40. 2008
    ..These data show that the mechanism of membrane solubilization is unique to an individual detergent. Our observations have significant implications for using different detergents to isolate membrane rafts from biological systems...
  83. doi request reprint Plasma angiotensin-converting enzyme in Alzheimer's disease
    Emma R L C Vardy
    Divison of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    J Alzheimers Dis 16:609-18. 2009
    ..Plasma ACE did not correlate with cognitive function. The observed reduction in plasma ACE in AD may reflect a general decrease in the zinc metalloprotease-mediated shedding of a subset of membrane-bound proteins...
  84. pmc Neprilysin, obesity and the metabolic syndrome
    K F Standeven
    Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    Int J Obes (Lond) 35:1031-40. 2011
    ....
  85. pmc Prion protein and Alzheimer disease
    Katherine A B Kellett
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
    Prion 3:190-4. 2009
    ..In Alzheimer disease, this feedback loop is disrupted, and the increased level of Abeta oligomers bind to PrP(C) and prevent it from regulating BACE1 activity...
  86. ncbi request reprint Glycosylation efficiency of Asn-Xaa-Thr sequons is independent of distance from the C-terminus in membrane dipeptidase
    Adrian R Walmsley
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U K
    Glycobiology 13:641-6. 2003
    ..These data demonstrate that the utilization of sequons in some proteins is independent of their distance from the C-terminus...
  87. ncbi request reprint Membrane raft actin deficiency and altered Ca2+-induced vesiculation in stomatin-deficient overhydrated hereditary stomatocytosis
    D Katie Wilkinson
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    Biochim Biophys Acta 1778:125-32. 2008
    ..Together these observations imply that the stomatin-actin association is important in maintaining the structure and in modulating the function of stomatin-containing membrane rafts in red cells...
  88. pmc The kinetics of phase separation in asymmetric membranes
    Elizabeth J Wallace
    School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, UK
    Biophys J 88:4072-83. 2005
    ....
  89. ncbi request reprint Cellular prion protein protects against reactive-oxygen-species-induced DNA damage
    Nicole T Watt
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK
    Free Radic Biol Med 43:959-67. 2007
    ....
  90. pmc The C-terminal domain, but not the interchain disulphide, is required for the activity and intracellular trafficking of aminopeptidase A
    Lisa D Ofner
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U K
    Biochem J 362:191-7. 2002
    ..In contrast, mutation of cysteine-43 to serine, which is involved in the disulphide-linkage of the APA homodimer, did not affect the enzymic activity, cellular location or rate of trafficking through the secretory pathway of APA...
  91. ncbi request reprint A broad-spectrum fluorescence-based peptide library for the rapid identification of protease substrates
    Daniel A Thomas
    Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    Proteomics 6:2112-20. 2006
    ....
  92. pmc Distance of sequons to the C-terminus influences the cellular N-glycosylation of the prion protein
    Adrian R Walmsley
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U K
    Biochem J 370:351-5. 2003
    ..Our findings indicate that sequon utilization in PrP is a co-translational process that precedes GPI anchor addition and, as such, will be greatly influenced by the dynamics of the translocon-oligosaccharyltransferase complex...
  93. ncbi request reprint Angiotensin-converting enzyme 2 and new insights into the renin-angiotensin system
    Daniel W Lambert
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
    Biochem Pharmacol 75:781-6. 2008
    ..We also discuss parallel developments in the study of collectrin, a catalytically inactive homologue of ACE2 with critical functions in the pancreas and kidney...
  94. doi request reprint PCSK9: an emerging target for treatment of hypercholesterolemia
    Christopher J Duff
    University of Leeds, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, Leeds LS2 9JT, UK
    Expert Opin Ther Targets 15:157-68. 2011
    ..Inhibiting the action of PCSK9 on the LDLR has emerged as a novel therapeutic target for hypercholesterolemia...
  95. ncbi request reprint Angiotensin-converting enzyme as a GPIase: a critical reevaluation
    Lilia Leisle
    Nat Med 11:1139-40. 2005
  96. ncbi request reprint Spontaneous release of glycosylphosphatidylinositol (GPI)-anchored renal dipeptidase from porcine renal proximal tubules
    Sung Wook Park
    Department of Pharmacy, College of Pharmacy, College of Natural Science, Chonnam National University, Kwangju, Korea
    Arch Pharm Res 25:80-5. 2002
    ..This enzyme then hydrolyses the GPI-anchored RDPase and is transferable. RDPase was purified following its release from the membrane by this simple and inexpensive method which may also be applied to other GPI-anchored proteins...
  97. ncbi request reprint Normalized proliferation of normal and psoriatic keratinocytes by suppression of sAPPalpha-release
    Christina Siemes
    Institute of Cell Biology and Bonner Forum Biomedizin, University of Bonn, Ulrich Haberland Strasse 61a, 53121 Bonn, Germany
    J Invest Dermatol 123:556-63. 2004
    ..The reversibility of these effects and the lack of toxicity underline the value of these inhibitors and suggest their therapeutic application in psoriatic skin diseases...
  98. pmc Nitric oxide inhibits the shedding of the glycosylphosphatidylinositol-anchored dipeptidase from porcine renal proximal tubules
    Sung Wook Park
    College of Pharmacy, Chonnam National University, 300 Yongbong Dong, Buk Gu, Kwangju 500 757, Korea
    Biochem J 364:211-8. 2002
    ..Therefore, this indicates a role for NO as an inhibitory regulator of the shedding of the GPI-anchored RDPase in acute renal failure...
  99. ncbi request reprint Protective effect of prion protein via the N-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells
    Ingrid Dupiereux
    Department of Human Histology CRPP, University of Liege, Sart Tilman, Liege, Belgium
    J Neurosci Res 86:653-9. 2008
    ....
  100. ncbi request reprint An ACE structure
    Nigel M Hooper
    Nat Struct Biol 10:155-7. 2003
  101. ncbi request reprint Glycosyl-phosphatidylinositol (GPI)-anchored renal dipeptidase is released by a phospholipase C in vivo
    Sung Wook Park
    College of Pharmacy, Hormone Research Center, Chonnam National University, Kwangju, Korea
    Kidney Blood Press Res 25:7-12. 2002
    ..This is the first direct evidence for cleavage of a human GPI-anchored protein by a responsible phospholipase C in vivo...