Hideaki Nagase

Summary

Affiliation: Imperial College
Country: UK

Publications

  1. pmc Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications
    Ngee H Lim
    Kennedy Institute of Rheumatology Division, Imperial College London, 65 Aspenlea Road, London W6 8LH, UK
    Biochem J 431:113-22. 2010
  2. pmc Defining requirements for collagenase cleavage in collagen type III using a bacterial collagen system
    Zhuoxin Yu
    Department of Biochemistry and Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Biol Chem 287:22988-97. 2012
  3. ncbi request reprint Structure and function of matrix metalloproteinases and TIMPs
    Hideaki Nagase
    Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, London W6 8LH, UK
    Cardiovasc Res 69:562-73. 2006
  4. doi request reprint Elucidating the function of non catalytic domains of collagenases and aggrecanases
    Hideaki Nagase
    Matrix Biology Department, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, United Kingdom
    Connect Tissue Res 49:169-74. 2008
  5. pmc Aggrecanases and cartilage matrix degradation
    Hideaki Nagase
    The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, UK
    Arthritis Res Ther 5:94-103. 2003
  6. ncbi request reprint Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4
    Christi Gendron
    Kennedy Institute of Rheumatology Division, Imperial College London, London W6 8LH, United Kingdom
    J Biol Chem 282:18294-306. 2007
  7. ncbi request reprint TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors
    Christi Gendron
    Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, W6 8LH, London, UK
    FEBS Lett 555:431-6. 2003
  8. ncbi request reprint Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing
    Masahide Kashiwagi
    Kennedy Institute of Rheumatology Division, Imperial College London, United Kingdom
    J Biol Chem 279:10109-19. 2004
  9. pmc The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP-3
    Linda Troeberg
    Kennedy Institute of Rheumatology, Imperial College London, Hammersmith, London, W6 8LH, UK
    Matrix Biol 28:463-9. 2009
  10. ncbi request reprint Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity
    Kazunari Fushimi
    Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom
    J Biol Chem 283:6706-16. 2008

Collaborators

Detail Information

Publications60

  1. pmc Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications
    Ngee H Lim
    Kennedy Institute of Rheumatology Division, Imperial College London, 65 Aspenlea Road, London W6 8LH, UK
    Biochem J 431:113-22. 2010
    ..These observations suggest that further mutation of the residues of N-TIMP-3 which make unique contacts with these metalloproteinases may allow discrimination between them...
  2. pmc Defining requirements for collagenase cleavage in collagen type III using a bacterial collagen system
    Zhuoxin Yu
    Department of Biochemistry and Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Biol Chem 287:22988-97. 2012
    ..The recombinant bacterial-human collagen system characterized here is a good model to investigate the specificity and mechanism of action of collagenases...
  3. ncbi request reprint Structure and function of matrix metalloproteinases and TIMPs
    Hideaki Nagase
    Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, London W6 8LH, UK
    Cardiovasc Res 69:562-73. 2006
    ..This review introduces the members of the MMP family and discusses their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology...
  4. doi request reprint Elucidating the function of non catalytic domains of collagenases and aggrecanases
    Hideaki Nagase
    Matrix Biology Department, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, United Kingdom
    Connect Tissue Res 49:169-74. 2008
    ..Such molecules will be attractive for therapy as they will be highly selective because they are based on the unique mechanism of each proteinase...
  5. pmc Aggrecanases and cartilage matrix degradation
    Hideaki Nagase
    The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, UK
    Arthritis Res Ther 5:94-103. 2003
    ....
  6. ncbi request reprint Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4
    Christi Gendron
    Kennedy Institute of Rheumatology Division, Imperial College London, London W6 8LH, United Kingdom
    J Biol Chem 282:18294-306. 2007
    ..Our studies suggest that ADAMTS-5 is a major aggrecanase in cartilage metabolism and pathology...
  7. ncbi request reprint TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors
    Christi Gendron
    Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, W6 8LH, London, UK
    FEBS Lett 555:431-6. 2003
    ..Little apoptosis of primary porcine chondrocytes is observed at an effective concentration of N-TIMP-3. These results suggest that TIMP-3 may be a candidate agent for use against cartilage degradation...
  8. ncbi request reprint Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing
    Masahide Kashiwagi
    Kennedy Institute of Rheumatology Division, Imperial College London, United Kingdom
    J Biol Chem 279:10109-19. 2004
    ..Finding of ADAMTS-4 in the interleukin-1alpha-treated porcine articular cartilage primarily as a 46-kDa form suggests that it exhibits a broader substrate spectrum in the tissue than originally considered...
  9. pmc The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP-3
    Linda Troeberg
    Kennedy Institute of Rheumatology, Imperial College London, Hammersmith, London, W6 8LH, UK
    Matrix Biol 28:463-9. 2009
    ..5-fold better K(i) value for full-length ADAMTS-5 than for the catalytic and disintegrin domain alone. We propose that the C-terminal domains of the enzymes affect the structure around the active site, favouring interaction with TIMP-3...
  10. ncbi request reprint Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity
    Kazunari Fushimi
    Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom
    J Biol Chem 283:6706-16. 2008
    ..However, removal of the spacer domain from ADAMTS-4 greatly enhanced more general proteolytic activity against non-aggrecan substrates, e.g. E. coli-expressed interglobular domain, fibromodulin, and carboxymethylated transferrin...
  11. pmc The second dimer interface of MT1-MMP, the transmembrane domain, is essential for ProMMP-2 activation on the cell surface
    Yoshifumi Itoh
    Department of Matrix Biology, Imperial College London, Hammersmith, London W6 8LH, UK
    J Biol Chem 283:13053-62. 2008
    ..Our finding provides new insight into the potential molecular arrangement of MT1-MMP contributing to its function on the cell surface...
  12. pmc LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage
    Kazuhiro Yamamoto
    Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, London, UK
    FASEB J 27:511-21. 2013
    ..Thus, LRP-1 dictates physiological and pathological catabolism of aggrecan in cartilage as a key modulator of the extracellular activity of ADAMTS-5...
  13. doi request reprint Dimerization of MT1-MMP during cellular invasion detected by fluorescence resonance energy transfer
    Yoshifumi Itoh
    The Kennedy Institute of Rheumatology, Imperial College London, London W6 8LH, UK
    Biochem J 440:319-26. 2011
    ..Our data indicate that cell-surface collagenolytic activity is regulated co-ordinately with cell migration events to enable penetration of the matrix physical barrier...
  14. pmc Differential regulation of extracellular tissue inhibitor of metalloproteinases-3 levels by cell membrane-bound and shed low density lipoprotein receptor-related protein 1
    Simone D Scilabra
    Department of Medicine, Imperial College London, London SW7 2AZ, United Kingdom
    J Biol Chem 288:332-42. 2013
    ..Extracellular levels of sLRP-1 can thus increase the half-life of TIMP-3 in the extracellular space, controlling the bioavailability of TIMP-3 to inhibit metalloproteinases...
  15. pmc Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases
    Linda Troeberg
    Kennedy Institute of Rheumatology Division, Imperial College London, 65 Aspenlea Rd, Hammersmith, London, W6 8LH, UK
    FASEB J 22:3515-24. 2008
    ..Studies with TIMP-3-null mouse cartilage indicated that CaPPS inhibition of aggrecan degradation is TIMP-3 dependent. These unique properties make CaPPS a prototypic disease-modifying agent for osteoarthritis...
  16. pmc Membrane type 1 matrix metalloproteinase is a crucial promoter of synovial invasion in human rheumatoid arthritis
    Mary Clare Miller
    Imperial College London, London, UK
    Arthritis Rheum 60:686-97. 2009
    ..The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane type 1 MMP (MT1-MMP), in synovial pannus invasiveness...
  17. pmc Cell surface collagenolysis requires homodimerization of the membrane-bound collagenase MT1-MMP
    Yoshifumi Itoh
    Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London W6 8LH, United Kingdom
    Mol Biol Cell 17:5390-9. 2006
    ..Our results introduce a new concept in that pericellular collagenolysis is regulated by correct molecular assembly of the membrane-anchored collagenase, thereby governing the directionality of the cell to migrate in tissue...
  18. pmc Pentosan polysulfate increases affinity between ADAMTS-5 and TIMP-3 through formation of an electrostatically driven trimolecular complex
    Linda Troeberg
    The Kennedy Institute of Rheumatology, University of Oxford, 65 Aspenlea Road, Hammersmith, London W6 8LH, UK
    Biochem J 443:307-15. 2012
    ..4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions...
  19. pmc Collagenase unwinds triple-helical collagen prior to peptide bond hydrolysis
    Linda Chung
    Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, UK
    EMBO J 23:3020-30. 2004
    ..Our results throw light on the basic mechanisms that control a wide range of biological and pathological processes associated with tissue remodelling...
  20. pmc Proteases involved in cartilage matrix degradation in osteoarthritis
    Linda Troeberg
    The Kennedy Institute of Rheumatology Division, Imperial College London, London, UK
    Biochim Biophys Acta 1824:133-45. 2012
    ..This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome...
  21. doi request reprint Zymography of metalloproteinases
    Linda Troeberg
    Imperial College London, London, United Kingdom
    Curr Protoc Protein Sci . 2004
    ..This unit presents a representative zymography protocol for the study of matrix metallopeptidases (MMPs)...
  22. pmc Structural insights into triple-helical collagen cleavage by matrix metalloproteinase 1
    Szymon W Manka
    Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, London W6 8LH, United Kingdom
    Proc Natl Acad Sci U S A 109:12461-6. 2012
    ..Interdomain flexing of the enzyme and a localized excursion of the collagen chain closest to the active site, facilitated by thermal loosening of the substrate, may lead to the first transition state of collagenolysis...
  23. doi request reprint Monitoring metalloproteinase activity using synthetic fluorogenic substrates
    Linda Troeberg
    Imperial College London, London, United Kingdom
    Curr Protoc Protein Sci . 2004
    ..Other fluorogenic peptides and protein substrates, together with non-fluorogenic alternatives, are also discussed...
  24. ncbi request reprint Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration
    Narayanapanicker Anilkumar
    Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Imperial College London, London, UK
    FASEB J 19:1326-8. 2005
    ..Taken together, palmitoylation of MT1-MMP is one of the key posttranslational modifications that determines MT1-MMP-dependent cell migration...
  25. ncbi request reprint Measurement of matrix metalloproteinase activities in the medium of cultured synoviocytes using zymography
    Linda Troeberg
    Imperial College, London, UK
    Methods Mol Biol 225:77-87. 2003
  26. ncbi request reprint E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP-2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A)
    Linda Troeberg
    Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, Hammersmith, London, W6 8LH UK
    Biochemistry 41:15025-35. 2002
    ..Similar models of interaction may apply to TIMP-4. The latter low-affinity site functions in conjunction with the active site of MMP-2 to generate a tight enzyme-inhibitor complex...
  27. ncbi request reprint Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry
    Robert Visse
    Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Rd, London W6 8LH, UK
    Circ Res 92:827-39. 2003
    ....
  28. ncbi request reprint Connective tissue remodeling: cross-talk between endothelins and matrix metalloproteinases
    David Abraham
    Centre for Rheumatology and Connective Tissue Diseases, Department of Medicine, Royal Free and University College Medical School, London, UK
    Curr Vasc Pharmacol 3:369-79. 2005
    ..In this review we present the cross-talk between the endothelins and the MMP-TIMP system and their implications in controlling the normal and abnormal tissue remodeling...
  29. pmc Engineering of tissue inhibitor of metalloproteinases mutants as potential therapeutics
    Hideaki Nagase
    The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK
    Arthritis Res 4:S51-61. 2002
    ..A potential therapeutic use of TIMP variants is discussed...
  30. ncbi request reprint Shear stress-induced shedding of soluble intercellular adhesion molecule-1 from saphenous vein endothelium
    Sabena Sultan
    Department of Vascular Surgery Charing Cross site, Imperial College London, St Dunstan s Road, London W6 8RP, UK
    FEBS Lett 564:161-5. 2004
    ..sICAM-1 was processed distal to Arg441, indicating that MMP-9, docking to ICAM-1, contributes to sICAM-1 shedding and attenuation of the shear stress-induced upregulation of ICAM-1...
  31. pmc Report on the Molecular Approaches to Osteoarthritis Symposium, Imperial College London, UK, 18-20 April 2004
    Jeremy Saklatvala
    Kennedy Institute of Rheumatology, Imperial College Faculty of Medicine, London, UK
    Arthritis Res Ther 6:203-7. 2004
  32. pmc Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity
    Alessandra Lo Cicero
    Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Via del Vespro 129, 90127 Palermo, Italy
    Matrix Biol 31:229-33. 2012
    ..Our findings raise the novel possibility that microvesicles may assist oligodendroglioma and rheumatoid synovial fibroblasts to invade through aggrecan-rich extracellular matrices...
  33. ncbi request reprint Matrix metalloproteinases in cancer
    Yoshifumi Itoh
    Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, U K
    Essays Biochem 38:21-36. 2002
    ..This review highlights recent developments with regard to the cellular and molecular mechanisms of MMPs that influence tumour cell growth, invasion and metastasis...
  34. ncbi request reprint Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair?
    Gillian Murphy
    Cancer Cell Biology, Department of Oncology, University of Cambridge, Cambridge, UK
    Nat Clin Pract Rheumatol 4:128-35. 2008
    ..Work on the development of effective biomarkers is also essential before an effective evaluation of the new generations of specific inhibitors can be made...
  35. ncbi request reprint Activation of membrane-type matrix metalloproteinase 3 zymogen by the proprotein convertase furin in the trans-Golgi network
    Tiebang Kang
    Department of Pharmacology, University of Minnesota, 321 Church Street S E, 6 120 Jackson Hall, Minneapolis, MN 55455, USA
    Cancer Res 62:675-81. 2002
    ..Thus, furin processes MT3-MMP zymogen in the trans-Golgi network, where they colocalize independently of their apparent enzyme-substrate relationship...
  36. ncbi request reprint Protein engineering of the tissue inhibitor of metalloproteinase 1 (TIMP-1) inhibitory domain. In search of selective matrix metalloproteinase inhibitors
    Shuo Wei
    Department of Biomedical Sciences, Florida Atlantic University, Boca Raton, Florida 33431, USA
    J Biol Chem 278:9831-4. 2003
    ..These selective TIMP variants may provide useful tools for investigation of biological roles of specific MMPs and for possible therapy of MMP-related diseases...
  37. ncbi request reprint Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 rgulates pro-MMP-2 activation
    Huiren Zhao
    Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA
    J Biol Chem 279:8592-601. 2004
    ..These results demonstrate that TIMP-3 is a major regulator of MT3-MMP activity and further underscores the unique interactions of TIMPs with MT-MMPs in the control of pericellular proteolysis...
  38. ncbi request reprint Low density lipoprotein receptor-related protein mediates endocytic clearance of pro-MMP-2.TIMP-2 complex through a thrombospondin-independent mechanism
    Herve Emonard
    CNRS UMR 6198, IFR 53 Biomolecules, Faculty of Medicine, F 51100 Reims, France
    J Biol Chem 279:54944-51. 2004
    ..TIMP-2 complex is a TSP-independent two-step process, involving (i) initial binding to the cell membrane in a RAP-insensitive manner and (ii) subsequent LRP-dependent (RAP-sensitive) internalization and degradation...
  39. ncbi request reprint Matrix metalloproteinase expression and function during fin regeneration in zebrafish: analysis of MT1-MMP, MMP2 and TIMP2
    Shan Bai
    Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
    Matrix Biol 24:247-60. 2005
    ..Taken together, these results indicate that MMPs have an important role during fin regeneration in zebrafish...
  40. ncbi request reprint Reactive site mutations in tissue inhibitor of metalloproteinase-3 disrupt inhibition of matrix metalloproteinases but not tumor necrosis factor-alpha-converting enzyme
    Shuo Wei
    Department of Biomedical Science, Florida Atlantic University, Boca Raton, Florida 33431, USA
    J Biol Chem 280:32877-82. 2005
    ....
  41. pmc TIMP-3 inhibits the procollagen N-proteinase ADAMTS-2
    Wei Man Wang
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA
    Biochem J 398:515-9. 2006
    ..In contrast, TIMP-3 is demonstrated to inhibit ADAMTS-2 in vitro with apparent Ki values of 160 and 602 nM, in the presence of heparin or without respectively; and TIMP-3 is shown to inhibit procollagen processing by cells...
  42. ncbi request reprint Individual Timp deficiencies differentially impact pro-MMP-2 activation
    Jane L English
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    J Biol Chem 281:10337-46. 2006
    ..Thus, TIMP-3 provides an inherent regulation over the kinetics of pro-MMP-2 processing, serving at a level distinct from that of TIMP-2 and TIMP-4...
  43. ncbi request reprint Structural features of the reprolysin atrolysin C and tissue inhibitors of metalloproteinases (TIMPs) interaction
    Antonio F M Pinto
    Department of Microbiology, University of Virginia, Charlottesville, 22908 0734, USA
    Biochem Biophys Res Commun 347:641-8. 2006
    ..This study is the first to shed light on the structural determinants required for the interaction between a SVMP and a TIMP, and suggests a structural basis for TIMP-3 inhibitory action and related proteins such as the ADAMs...
  44. pmc Crystal structure of an active form of human MMP-1
    Shalini Iyer
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK
    J Mol Biol 362:78-88. 2006
    ..Comparing this structure with the human proMMP-1 shows significant structural differences, mainly in the relative orientation of the hemopexin domain, between the pro form and active form of the human enzyme...
  45. ncbi request reprint Matrix metalloproteinase triple-helical peptidase activities are differentially regulated by substrate stability
    Dmitriy Minond
    Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431 0991, USA
    Biochemistry 43:11474-81. 2004
    ..These results demonstrate that collagenolytic MMPs have subtle differences in their abilities to hydrolyze triple helices and may explain the relative collagen specificity of MMP-1...
  46. ncbi request reprint Catalytic properties of ADAM12 and its domain deletion mutants
    Jonas Jacobsen
    Department of Biomedical Sciences and Biotech Research and Innovation Centre BRIC, University of Copenhagen, Ole Maaløes Vej 5, DK 2200 Copenhagen, Denmark
    Biochemistry 47:537-47. 2008
    ..These results indicate unique enzymatic properties of ADAM12 among the members of the ADAM family of metalloproteinases...
  47. ncbi request reprint Tissue inhibitor of metalloproteinases-3 induces apoptosis in melanoma cells by stabilization of death receptors
    Matti Ahonen
    Centre for Biotechonology, University of Turku, Finland
    Oncogene 22:2121-34. 2003
    ..Taken together, these results show that TIMP-3 promotes apoptosis in melanoma cells through stabilization of three distinct death receptors and activation of their apoptotic signaling cascade through caspase-8...
  48. ncbi request reprint Analysis of TIMP expression and activity
    Linda Troeberg
    Methods Mol Med 135:251-67. 2007
    ....
  49. ncbi request reprint The expression of novel membrane-type matrix metalloproteinase isoforms is required for normal development of zebrafish embryos
    Jinsong Zhang
    Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
    Matrix Biol 22:279-93. 2003
    ..Axis markers indicated that these effects likely involved processes occurring later than 10 h of embryogenesis...
  50. ncbi request reprint Analysis of matrix metalloproteinase triple-helical peptidase activity with substrates incorporating fluorogenic L- or D-amino acids
    Janelle L Lauer-Fields
    Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431 0991, USA
    Anal Biochem 321:105-15. 2003
    ....
  51. ncbi request reprint Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis
    Frank R Murphy
    Liver Group, Division of Infection, Inflammation and Repair, University of Southampton, Hampshire SO16 6YD, United Kingdom
    J Biol Chem 277:11069-76. 2002
    ..We conclude that TIMP-1 inhibits apoptosis of activated HSC via MMP inhibition...
  52. ncbi request reprint Matrix metalloproteinase 1 interacts with neuronal integrins and stimulates dephosphorylation of Akt
    Katherine Conant
    Departments of Neurology and Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Biol Chem 279:8056-62. 2004
    ..Together, these results suggest that MMP-1 can stimulate dephosphorylation of Akt and neuronal death through a non-proteolytic mechanism that involves changes in integrin signaling...
  53. pmc Development of a solid-phase assay for analysis of matrix metalloproteinase activity
    Janelle L Lauer-Fields
    Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431 0991, USA
    J Biomol Tech 15:305-16. 2004
    ..The solid-phase assay is suitably flexible to allow studies of virtually any proteolytic enzyme for which appropriate substrates and antibodies are available...
  54. ncbi request reprint X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding
    Daniela Jozic
    Max Planck Institut fur Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    J Biol Chem 280:9578-85. 2005
    ..This is the first evidence of mobility of the Hpx domain in relation to the catalytic domain, providing an important clue toward the understanding of the collagenase-collagen interaction and subsequent collagenolysis...
  55. ncbi request reprint The roles of substrate thermal stability and P2 and P1' subsite identity on matrix metalloproteinase triple-helical peptidase activity and collagen specificity
    Dmitriy Minond
    Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431 0991, USA
    J Biol Chem 281:38302-13. 2006
    ..Further exploration of MMP active sites and exosites, in combination with substrate conformation, may prove valuable for additional dissection of collagenolysis and yield information useful in the design of more selective MMP inhibitors...
  56. ncbi request reprint Substrate conformation modulates aggrecanase (ADAMTS-4) affinity and sequence specificity. Suggestion of a common topological specificity for functionally diverse proteases
    Janelle L Lauer-Fields
    Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, Florida 33431 0991, USA
    J Biol Chem 282:142-50. 2007
    ..The triple-helical and single-stranded poly(Pro) II helical peptides represent the first synthetic substrates successfully designed for aggrecanases...
  57. pmc Identification of a novel 82 kDa proMMP-9 species associated with the surface of leukaemic cells: (auto-)catalytic activation and resistance to inhibition by TIMP-1
    Christian Ries
    Division of Clinical Chemistry and Clinical Biochemistry in the Surgical Department, Ludwig Maximilians University of Munich, 80336 Munich, Germany
    Biochem J 405:547-58. 2007
    ..Thus, the 82 kDa proMMP-9 expressed on the surface of malignant cells may escape inhibition by natural TIMP-1, thereby facilitating cellular invasion in vivo...
  58. ncbi request reprint Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling
    Charlotte Kopitz
    Institut für Experimentelle Onkologie und Therapieforschung, Universitat Munchen, Munich, Germany
    Cancer Res 67:8615-23. 2007
    ..Similar TIMP-1-associated changes in gene expression were detected in livers of patients with metastatic colorectal cancer. The newly identified role of TIMP-1 to create a prometastatic niche may also explain the TIMP-1 paradoxon...
  59. pmc Screening of potential a disintegrin and metalloproteinase with thrombospondin motifs-4 inhibitors using a collagen model fluorescence resonance energy transfer substrate
    Janelle L Lauer-Fields
    Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
    Anal Biochem 373:43-51. 2008
    ..Selective inhibitors for ADAMTS-4 would allow a more definitive evaluation of this protease in osteoarthritis and also represent a potential next generation in metalloproteinase therapeutics...
  60. ncbi request reprint Selective hydrolysis of triple-helical substrates by matrix metalloproteinase-2 and -9
    Janelle L Lauer-Fields
    Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, Florida 33431 0991, USA
    J Biol Chem 278:18140-5. 2003
    ..THPs were found to provide highly selective substrates for members of the MMP family and can be used to evaluate active MMP production in cellular systems...

Research Grants14

  1. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 2001
    ..The principal investigator also proposes to examine the role of cell surface TIMP-2 in this activation process. ..
  2. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 2000
    ..The principal investigator also proposes to examine the role of cell surface TIMP-2 in this activation process. ..
  3. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 1999
    ..The principal investigator also proposes to examine the role of cell surface TIMP-2 in this activation process. ..
  4. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 1992
    ....
  5. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 1991
    ....
  6. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 1990
    ....
  7. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 1993
    ....
  8. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 2002
    ..The principal investigator also proposes to examine the role of cell surface TIMP-2 in this activation process. ..