Research Topics
Genomes and Genes | N M HooperSummaryAffiliation: University of Leeds Country: UK Publications
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Publications
Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACEMonika 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...
Glypican-1 facilitates prion conversion in lipid raftsNigel M Hooper
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
J Neurochem 116:721-5. 2011....
Foreword: lipid rafts/biophysics, cell signalling, trafficking and processingNigel 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
Determination of glycosyl-phosphatidylinositol membrane protein anchorageN 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...
Mechanism of the metal-mediated endocytosis of the prion proteinNigel 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...
A new take on prions: preventing Alzheimer's diseaseNigel 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...
Prion disease: close encounters of the cellular kindNigel 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...
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....
The search for alpha-secretase and its potential as a therapeutic approach to Alzheimer s diseaseN M Hooper
Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, UK
Curr Med Chem 9:1107-19. 2002....
Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion proteinN 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....
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....
Protein processing mechanisms: from angiotensin-converting enzyme to Alzheimer's diseaseN 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....
Glycosyl-phosphatidylinositol anchored membrane enzymesN 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...
Proteases: a primerNigel 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...
Roles of the juxtamembrane and extracellular domains of angiotensin-converting enzyme in ectodomain sheddingS 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...
Isolation and characterization of two distinct low-density, Triton-insoluble, complexes from porcine lung membranesE T Parkin
Department of Biochemistry and Molecular Biology, University of Leeds, U K
Biochem J 319:887-96. 1996....
Differential effects of glycosphingolipids on the detergent-insolubility of the glycosylphosphatidylinositol-anchored membrane dipeptidaseE T Parkin
School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
Biochem J 358:209-16. 2001....
Proteolytic fragmentation reveals the oligomeric and domain structure of porcine aminopeptidase AJ R Hesp
Department of Biochemistry and Molecular Biology, University of Leeds, U K
Biochemistry 36:3000-7. 1997....
Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolismGillian 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...
Membrane-associated zinc peptidase families: comparing ACE and ACE2J 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...
The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor proteinTobias 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...
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-alphaEdward 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...
Site-directed mutagenesis of conserved cysteine residues in porcine membrane dipeptidase. Cys 361 alone is involved in disulfide-linked dimerizationS 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...
Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzymeG 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...
Role of ADAMs in the ectodomain shedding and conformational conversion of the prion proteinDavid 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...
Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cellsFiona 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...
Reactive oxygen species-mediated beta-cleavage of the prion protein in the cellular response to oxidative stressNicole 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...
Assigning functions to distinct regions of the N-terminus of the prion protein that are involved in its copper-stimulated, clathrin-dependent endocytosisDavid 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...
Glycosylation and GPI anchorage of the prion proteinN 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
Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat regionW S Perera
School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
Curr Biol 11:519-23. 2001....
Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependenceJodie L Guy
School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom
Biochemistry 42:13185-92. 2003....
Proteolytic mechanisms in amyloid-beta metabolism: therapeutic implications for Alzheimer's diseaseEmma 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....
The prion protein and neuronal zinc homeostasisNicole 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...
Glypican-1 mediates both prion protein lipid raft association and disease isoform formationDavid 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...
The carboxyl terminus of Dictyostelium discoideum protein 1I encodes a functional glycosyl-phosphatidylinositol signal sequenceB 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...
Angiotensin-converting enzyme-2: a molecular and cellular perspectiveF J Warner
School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom
Cell Mol Life Sci 61:2704-13. 2004....
Molecular cloning and expression in COS-1 cells of pig kidney aminopeptidase PR 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...
The response of neurones and glial cells to elevated copperN 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...
N-glycans, not the GPI anchor, mediate the apical targeting of a naturally glycosylated, GPI-anchored protein in polarised epithelial cellsSusan 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...
The prion protein and lipid raftsDavid 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...
The low-density lipoprotein receptor-related protein 1 (LRP1) mediates the endocytosis of the cellular prion proteinDavid 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)...
Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor proteinEdward 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...
Ectodomain shedding of cystinyl aminopeptidase from human placental membranesL 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...
The N-terminal region of the prion protein ectodomain contains a lipid raft targeting determinantAdrian 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...
ADAMs family members as amyloid precursor protein alpha-secretasesTobias 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....
Sphingomyelin chain length influences the distribution of GPI-anchored proteins in rafts in supported lipid bilayersAshley 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....
Contamination of nuclear fractions with plasma membrane lipid raftsYee 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....
Characterization of the glycosyl-phosphatidylinositol-anchored human renal dipeptidase reveals that it is more extensively glycosylated than the pig enzymeN M Hooper
Department of Biochemistry, University of Leeds, U K
Biochem J 265:429-33. 1990....
The cloning and functional expression of human pancreatic aminopeptidase PG S Cottrell
School of Biochemistry and Molecular Biology, University of Leeds, UK
Biochem Soc Trans 26:S248. 1998
The involvement of lipid rafts in Alzheimer's diseaseJoanna 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)...
Emerging therapeutics for Alzheimer's diseaseEmma 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...
Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family studyGillian 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...
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 CRosa-Maria Canet-Aviles
Academic Unit of Cardiovascular Medicine, University of Leeds, Leeds, UK
Brain Res Mol Brain Res 102:62-72. 2002....
ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitorsAnthony 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...
The angiotensin-converting enzyme gene family: genomics and pharmacologyAnthony 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...
Role of lipid rafts in the processing of the pathogenic prion and Alzheimer's amyloid-beta proteinsDavid 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...
Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomainDaniel 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...
Emerging and potential therapies for Alzheimer's diseaseHeledd 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...
The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pillAmy 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...
Ligand-stimulated VEGFR2 signaling is regulated by co-ordinated trafficking and proteolysisAlexander 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...
Tethering the N-terminus of the prion protein compromises the cellular response to oxidative stressFanning Zeng
School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK
J Neurochem 84:480-90. 2003....
Secretase-mediated cell surface shedding of the angiotensin-converting enzymeEdward 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...
The Caenorhabditis elegans orthologue of mammalian puromycin-sensitive aminopeptidase has roles in embryogenesis and reproductionDarren 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...
Identification of critical active-site residues in angiotensin-converting enzyme-2 (ACE2) by site-directed mutagenesisJodie 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...
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...
Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor proteinJoanna 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...
The ectodomain shedding of angiotensin-converting enzyme is independent of its localisation in lipid raftsEdward 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...
Dual mechanisms for shedding of the cellular prion proteinEdward 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...
ACE2: from vasopeptidase to SARS virus receptorAnthony 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...
A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidaseS 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...
Plasma angiotensin-converting enzyme in Alzheimer's diseaseEmma 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...
Visualization of detergent solubilization of membranes: implications for the isolation of raftsAshley 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...
alpha-cleavage of the prion protein occurs in a late compartment of the secretory pathway and is independent of lipid raftsAdrian 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...
Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line, SH-SY5YLeigh D Plant
School of Biomedical Sciences, University of Leeds, Leeds, UK
Neuroreport 13:1553-6. 2002....
Reactive oxygen species (ROS)-mediated beta-cleavage of the prion protein in the mechanism of the cellular response to oxidative stressN 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...
Glycosylation efficiency of Asn-Xaa-Thr sequons is independent of distance from the C-terminus in membrane dipeptidaseAdrian 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...
Cellular prion protein protects against reactive-oxygen-species-induced DNA damageNicole 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....
Prion protein and Alzheimer diseaseKatherine 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...
The kinetics of phase separation in asymmetric membranesElizabeth J Wallace
School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, UK
Biophys J 88:4072-83. 2005....
Membrane raft actin deficiency and altered Ca2+-induced vesiculation in stomatin-deficient overhydrated hereditary stomatocytosisD 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...
Neprilysin, obesity and the metabolic syndromeK 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....
Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptorChristopher 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...
A broad-spectrum fluorescence-based peptide library for the rapid identification of protease substratesDaniel 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....
Distance of sequons to the C-terminus influences the cellular N-glycosylation of the prion proteinAdrian 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...
The C-terminal domain, but not the interchain disulphide, is required for the activity and intracellular trafficking of aminopeptidase ALisa 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...
Angiotensin-converting enzyme 2 and new insights into the renin-angiotensin systemDaniel 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...
PCSK9: an emerging target for treatment of hypercholesterolemiaChristopher 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..However, further research is required to fully understand the biological role of PCSK9 and whether its inhibition may have adverse effects in certain groups of patients, for example, those with liver disease...
Angiotensin-converting enzyme as a GPIase: a critical reevaluationLilia Leisle
Nat Med 11:1139-40. 2005
Spontaneous release of glycosylphosphatidylinositol (GPI)-anchored renal dipeptidase from porcine renal proximal tubulesSung 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...
Protective effect of prion protein via the N-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cellsIngrid Dupiereux
Department of Human Histology CRPP, University of Liege, Sart Tilman, Liege, Belgium
J Neurosci Res 86:653-9. 2008....
Nitric oxide inhibits the shedding of the glycosylphosphatidylinositol-anchored dipeptidase from porcine renal proximal tubulesSung 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...
An ACE structureNigel M Hooper
Nat Struct Biol 10:155-7. 2003
Normalized proliferation of normal and psoriatic keratinocytes by suppression of sAPPalpha-releaseChristina 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...
Isolation and characterization of glycosylphosphatidylinositol-anchored peptides by hydrophilic interaction chromatography and MALDI tandem mass spectrometryMiren J Omaetxebarria
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK 5230 Odense M, Denmark
Anal Chem 78:3335-41. 2006..Thus, the methodology described herein may enable sensitive and specific detection of GPI-anchored peptides in large-scale proteomic studies of plasma membrane proteins...
Changes of angiotensin-converting enzyme activity in the pancreas of chronic hypoxia and acute pancreatitisSiu Po Ip
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin N.T, Hong Kong, PR China
Int J Biochem Cell Biol 35:944-54. 2003..All these data suggest that increased activity of pancreatic ACE in chronic hypoxia and acute pancreatitis could have implications for pancreatic physiology and pathophysiology...
Glycosyl-phosphatidylinositol (GPI)-anchored renal dipeptidase is released by a phospholipase C in vivoSung 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...
