furin

Summary

Summary: A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.

Top Publications

  1. pmc Proteolytic activation of tick-borne encephalitis virus by furin
    K Stadler
    Institute of Virology, University of Vienna, Austria
    J Virol 71:8475-81. 1997
  2. pmc Furin at the cutting edge: from protein traffic to embryogenesis and disease
    Gary Thomas
    Vollum Institute, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nat Rev Mol Cell Biol 3:753-66. 2002
  3. pmc The infectivity of prM-containing partially mature West Nile virus does not require the activity of cellular furin-like proteases
    Swati Mukherjee
    Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, 33 North Drive, Building 33, Room 2E19A 2, Bethesda, MD 20892, USA
    J Virol 85:12067-72. 2011
  4. pmc Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases
    Gero L Becker
    Institute of Pharmaceutical Chemistry, Philipps University, 35032 Marburg, Germany
    J Biol Chem 287:21992-2003. 2012
  5. pmc Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3
    S P Smeekens
    Howard Hughes Medical Institute, Department of Biochemistry, University of Chicago, IL 60637
    Proc Natl Acad Sci U S A 89:8822-6. 1992
  6. ncbi The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 281:30561-72. 2006
  7. pmc Thyroid hormone promotes cell invasion through activation of furin expression in human hepatoma cell lines
    Ruey Nan Chen
    Department of Biochemistry, Chang Gung University, 259 Wen hwa 1 Road, Taoyuan 333, Taiwan, Republic of China
    Endocrinology 149:3817-31. 2008
  8. ncbi Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin
    Ricardo Lopez De Cicco
    Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 65:4162-71. 2005
  9. ncbi Insights from bacterial subtilases into the mechanisms of intramolecular chaperone-mediated activation of furin
    Ujwal Shinde
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97229, USA
    Methods Mol Biol 768:59-106. 2011
  10. ncbi RSPO4 is the major gene in autosomal-recessive anonychia and mutations cluster in the furin-like cysteine-rich domains of the Wnt signaling ligand R-spondin 4
    Nadina Ortiz Brüchle
    Department of Human Genetics, RWTH Aachen University, Aachen, Germany
    J Invest Dermatol 128:791-6. 2008

Detail Information

Publications315 found, 100 shown here

  1. pmc Proteolytic activation of tick-borne encephalitis virus by furin
    K Stadler
    Institute of Virology, University of Vienna, Austria
    J Virol 71:8475-81. 1997
    ..out in vivo and in vitro studies with tick-borne encephalitis (TBE) virus to investigate the possible role of furin in this process as well as the functional consequences of prM cleavage...
  2. pmc Furin at the cutting edge: from protein traffic to embryogenesis and disease
    Gary Thomas
    Vollum Institute, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Nat Rev Mol Cell Biol 3:753-66. 2002
    b>Furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway...
  3. pmc The infectivity of prM-containing partially mature West Nile virus does not require the activity of cellular furin-like proteases
    Swati Mukherjee
    Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, 33 North Drive, Building 33, Room 2E19A 2, Bethesda, MD 20892, USA
    J Virol 85:12067-72. 2011
    Cleavage of the flavivirus prM protein by a cellular furin-like protease is a hallmark of virion maturation. While this cleavage is a required step in the viral life cycle, it can be inefficient...
  4. pmc Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases
    Gero L Becker
    Institute of Pharmaceutical Chemistry, Philipps University, 35032 Marburg, Germany
    J Biol Chem 287:21992-2003. 2012
    Optimization of our previously described peptidomimetic furin inhibitors was performed and yielded several analogs with a significantly improved activity...
  5. pmc Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3
    S P Smeekens
    Howard Hughes Medical Institute, Department of Biochemistry, University of Chicago, IL 60637
    Proc Natl Acad Sci U S A 89:8822-6. 1992
    ..viruses expressing rat proinsulin I coinfected into COS-7 cells with recombinant vaccinia virus expressing human furin, human PC2, mouse PC3 (subtilisin-related proprotein convertases 1-3, respectively), or yeast Kex2 indicate that ..
  6. ncbi The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 281:30561-72. 2006
    ..mutations R218S, F216L, and D374Y associated with hypercholesterolemia result in total or partial loss of furin/PC5/6A processing at the motif RFHR218 downward arrow...
  7. pmc Thyroid hormone promotes cell invasion through activation of furin expression in human hepatoma cell lines
    Ruey Nan Chen
    Department of Biochemistry, Chang Gung University, 259 Wen hwa 1 Road, Taoyuan 333, Taiwan, Republic of China
    Endocrinology 149:3817-31. 2008
    ..The gene encoding furin, as previously identified by cDNA microarray, is known to be up-regulated by T(3) treatment, and stimulated furin ..
  8. ncbi Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin
    Ricardo Lopez De Cicco
    Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 65:4162-71. 2005
    b>Furin, a potent proprotein convertase involved in activation of several cancer-related substrates, is synthesized as an inactive zymogen, thus minimizing the occurrence of premature enzymatic activity that would lead to inappropriate ..
  9. ncbi Insights from bacterial subtilases into the mechanisms of intramolecular chaperone-mediated activation of furin
    Ujwal Shinde
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97229, USA
    Methods Mol Biol 768:59-106. 2011
    ..from the folding and activation of prokaryotic subtilisin, discuss how this has molded our understanding of furin maturation, and foray into the concept of pH sensors, which may represent a paradigm that PCs (and possibly other ..
  10. ncbi RSPO4 is the major gene in autosomal-recessive anonychia and mutations cluster in the furin-like cysteine-rich domains of the Wnt signaling ligand R-spondin 4
    Nadina Ortiz Brüchle
    Department of Human Genetics, RWTH Aachen University, Aachen, Germany
    J Invest Dermatol 128:791-6. 2008
    ..Thus, we postulate that RSPO4 mutations preferentially cluster in the furin-like cysteine-rich domains of R-spondin 4, which is in line with experimental data proposing that for beta-catenin ..
  11. pmc Processing of the Ebola virus glycoprotein by the proprotein convertase furin
    V E Volchkov
    Institut fur Virologie, Philipps Universitat Marburg, 35011 Marburg, Germany
    Proc Natl Acad Sci U S A 95:5762-7. 1998
    ..GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo ..
  12. pmc Proteolytic activation of the spike protein at a novel RRRR/S motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells
    Yoshiyuki Yamada
    Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
    J Virol 83:8744-58. 2009
    ..S) protein of the coronavirus (CoV) infectious bronchitis virus (IBV) is cleaved into S1 and S2 subunits at the furin consensus motif RRFRR(537)/S in virus-infected cells...
  13. pmc Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-β1: role of TGF-β1 in HCV replication
    Lance D Presser
    Department of Microbiology and Immunology, H M Bligh Cancer Research Laboratories, Rosalind Franklin University of Medicine and Science, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA
    Virology 412:284-96. 2011
    ..Using siRNA approach we demonstrated that HCV-induced furin and thrombospondin-1 (TSP-1) are involved in the proteolytic activation of TGF-β1...
  14. pmc Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes
    Thomas J Carney
    Max Planck Institute of Immunobiology, Georges Koehler Laboratory, Freiburg, Germany
    PLoS Genet 6:e1000907. 2010
    ..In addition, the novel genes might prove helpful to unravel the molecular nature of thus far unresolved cases of the human disease...
  15. pmc Crimean-congo hemorrhagic fever virus glycoprotein precursor is cleaved by Furin-like and SKI-1 proteases to generate a novel 38-kilodalton glycoprotein
    Angela J Sanchez
    Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Mail Stop G 14, 1600 Clifton Rd, Atlanta, GA 30333, USA
    J Virol 80:514-25. 2006
    ..A highly conserved furin/proprotein convertase (PC) cleavage site motif (RSKR247) is located between the variable N-terminal region that is ..
  16. ncbi The proprotein convertase furin in human trophoblast: Possible role in promoting trophoblast cell migration and invasion
    Z Zhou
    Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China
    Placenta 30:929-38. 2009
    b>Furin, a proprotein convertase (PC), is ubiquitously expressed and implicated in many physiological and pathological processes. This study is aimed to identify the role of furin in human trophoblast invasion and migration...
  17. ncbi Furin regulates the intracellular activation and the uptake rate of cell surface-associated MT1-MMP
    A G Remacle
    The Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Oncogene 25:5648-55. 2006
    ..There are two potential furin cleavage motifs, R(89)-R-P-R-C(93) and R(108)-R-K-R-Y(112), in the prodomain sequence of MT1-MMP...
  18. ncbi Combination of the 2A/furin technology with an animal component free cell line development platform process
    Thomas Jostock
    Process Sciences and Production, Novartis Biologics, Basel, Switzerland
    Appl Microbiol Biotechnol 87:1517-24. 2010
    The recently described 2A/furin technology combines both chains of the antibody in a single open reading frame. Upon translation and secretion, the peptide is processed by the cell to generate native fully functional IgG antibodies...
  19. pmc Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin
    Pei Zhi Cheryl Chia
    The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia
    J Cell Sci 124:2401-13. 2011
    The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane...
  20. ncbi Recycling of furin from the plasma membrane. Functional importance of the cytoplasmic tail sorting signals and interaction with the AP-2 adaptor medium chain subunit
    M Teuchert
    Institut für Virologie der Philipps Universität Marburg, Robert Koch Strasse 17, 35037 Marburg, Germany
    J Biol Chem 274:36781-9. 1999
    The predominant intracellular localization of the eukaryotic subtilisin-like endoprotease furin is the trans-Golgi network (TGN), but a small fraction is also found on the cell surface...
  21. ncbi Proteolytic activation of respiratory syncytial virus fusion protein. Cleavage at two furin consensus sequences
    G Zimmer
    , , , D-30559 Hannover, Germany
    J Biol Chem 276:31642-50. 2001
    ..processed at the multibasic sequence KKRKRR(136) into the subunits F(1) and F(2) by the cellular protease furin. This maturation process is essential for the F protein to gain fusion competence...
  22. ncbi Functional importance of dengue virus maturation: infectious properties of immature virions
    Izabela A Zybert
    Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    J Gen Virol 89:3047-51. 2008
    ..of flavivirus particles from infected cells, the viral surface protein prM is cleaved to M by the cellular enzyme furin. For dengue virus (DENV), this maturation process appears to be very inefficient since a high proportion of ..
  23. pmc Furin-mediated cleavage of the feline foamy virus Env leader protein
    Verena Geiselhart
    Abt Genomveränderung und Carcinogenese, Forschungsschwerpunkt Infektion und Krebs, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
    J Virol 78:13573-81. 2004
    ..biochemical, and biophysical methods, we show that the feline foamy virus (FFV) Elp is released by a cellular furin-like protease, most likely furin itself, generating an Elp protein consisting of 127 amino acid residues...
  24. pmc Prototype foamy virus envelope glycoprotein leader peptide processing is mediated by a furin-like cellular protease, but cleavage is not essential for viral infectivity
    Anja Duda
    Institut fur Virologie, Medizinische Fakultät Carl Gustav Carus, Technische Universitat Dresden, Fetscherstr 74, 01307 Dresden, Germany
    J Virol 78:13865-70. 2004
    ..Here we provide strong evidence that furin itself or a furin-like protease and not the signal peptidase complex is responsible for both processing events...
  25. ncbi Processing of CD109 by furin and its role in the regulation of TGF-beta signaling
    S Hagiwara
    Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Oncogene 29:2181-91. 2010
    ..as a 205 kDa glycoprotein, which is then processed in the Golgi apparatus into 180 kDa and 25 kDa proteins by furin (furinase)...
  26. pmc A new common integration site, Int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences
    William Lowther
    Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, Bethesda, MD 20892, USA
    J Virol 79:10093-6. 2005
    ..that is 2 to 3 kb 5' of the transcription initiation site of a gene, 2610028F08RIK, whose gene product contains furin-like and thrombospondin-like sequences...
  27. ncbi Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7 and the disintegrin metalloprotease ADAM10
    E Lopez-Perez
    IPMC du CNRS, UMR6097, Valbonne, France
    J Neurochem 76:1532-9. 2001
    ..Here we report on the fact that the furin-deficient LoVo cells are devoid of regulated PKC-dependent sAPPalpha secretion and therefore represent an ..
  28. ncbi The proprotein convertases
    D F Steiner
    Howard Hughes Medical Institute, University of Chicago, 5841 South Maryland Avenue, MC 1028, Chicago, IL 60637, USA
    Curr Opin Chem Biol 2:31-9. 1998
    ..b>Furin (SPC1) has emerged as one of the major processing enzymes of the constitutive secretory pathway and its ..
  29. pmc Evidence that furin is an authentic transforming growth factor-beta1-converting enzyme
    C M Dubois
    Immunology Division and Department of Pharmacology, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Canada
    Am J Pathol 158:305-16. 2001
    ..PC) recognition motifs and has previously demonstrated that this PC-like cleavage site is correctly cleaved by furin, a member of the PC family...
  30. ncbi Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160
    S Hallenberger
    Institut fur Virologie, Philips Universität Marburg, Germany
    Nature 360:358-61. 1992
    ..found that the enzyme activating the haemagglutinin of fowl plague virus (FPV), an avian influenza virus, is furin. Furin, a subtilisin-like eukaryotic endoprotease, has a substrate specificity for the consensus amino-acid ..
  31. ncbi Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2
    H Sato
    Department of Molecular Virology and Oncology, Kanazawa University, Japan
    FEBS Lett 393:101-4. 1996
    ..MT1-MMP possesses a unique amino acid sequence Arg-Arg-Lys-Arg111 which is a potential recognition sequence for furin-like proteases (Nature, 370 (1994) 61-65)...
  32. ncbi Prediction of proprotein convertase cleavage sites
    Peter Duckert
    Center for Biological Sequence Analysis, BioCentrum DTU, Technical University of Denmark, Building 208, DK 2800 Lyngby, Denmark
    Protein Eng Des Sel 17:107-12. 2004
    ..In mammals, seven members have been identified, with furin being the one first discovered and best characterized...
  33. ncbi Soluble form of the (pro)renin receptor generated by intracellular cleavage by furin is secreted in plasma
    Christelle Cousin
    Institut National de la Santé et de la Recherche Médicale and Collège de France, Paris, France
    Hypertension 53:1077-82. 2009
    ..We identified furin as the protease responsible for the shedding of endogenous (P)RR based on the following: LoVo colon carcinoma ..
  34. ncbi Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase Furin
    A J Roebroek
    Laboratory for Molecular Oncology, Experimental Genetics Group, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology VIB, Herestraat 49, B 3000 Leuven
    Development 125:4863-76. 1998
    We have examined the role of Furin in postimplantation-stage mouse embryos by analyzing both the expression pattern of fur mRNA and the developmental consequences of a loss-of-function mutation at the fur locus. At early stages (day 7...
  35. ncbi Processing of transforming growth factor beta 1 precursor by human furin convertase
    C M Dubois
    Department of Pediatrics, Faculty of Medicine, Universite de Sherbrooke, Quebec, Canada
    J Biol Chem 270:10618-24. 1995
    ..To determine whether cleavage of pro-TGF beta 1 can be achieved by the furin convertase in vitro, purified precursor was incubated in the presence of a truncated/secreted form of the enzyme...
  36. ncbi Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer
    Robert E Page
    Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cell Oncol 29:289-99. 2007
    ..We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression.
  37. ncbi Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus
    Sigrid Elshuber
    Institute of Virology, University of Vienna, Kinderspitalgasse 15, A 1095 Vienna, Austria
    J Gen Virol 84:183-91. 2003
    ..Shortly before release from the cell, prM is cleaved by the host protease furin to yield mature virions...
  38. ncbi Structure of the immature dengue virus at low pH primes proteolytic maturation
    I Mei Yu
    Department of Biological Sciences, 915 West State Street, Purdue University, West Lafayette, IN 47907 2054, USA
    Science 319:1834-7. 2008
    ..the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6...
  39. pmc Autocatalytic activation of the furin zymogen requires removal of the emerging enzyme's N-terminus from the active site
    Katarzyna Gawlik
    Burnham Institute for Medical Research, La Jolla, California, United States of America
    PLoS ONE 4:e5031. 2009
    Before furin can act on protein substrates, it must go through an ordered process of activation...
  40. ncbi Anthrax toxin: receptor binding, internalization, pore formation, and translocation
    John A T Young
    Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Annu Rev Biochem 76:243-65. 2007
    ....
  41. ncbi Knock-out mouse models of proprotein convertases: unique functions or redundancy?
    John W M Creemers
    Laboratory of Biochemical Neuroendocrinology, Center for Human Genetics K U Leuven, Belgium
    Front Biosci 13:4960-71. 2008
    ..at basic residues within the general motif (K/R)-(X)-(K/R) is mediated by the proprotein convertases PC1/3, PC2, Furin, PACE4, PC4, PC5 and PC7, whereas the proteolysis of precursors within hydrophobic residues performed by the ..
  42. ncbi Elevated furin expression in aggressive human head and neck tumors and tumor cell lines
    D E Bassi
    Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Mol Carcinog 31:224-32. 2001
    Pro-protein convertases (PCs) are proteases that recognize and cleave precursor proteins. Furin, a well-studied PC, is ubiquitously expressed, and it has been implicated in many physiological and pathological processes...
  43. ncbi Furin-dependent intracellular activation of the human stromelysin-3 zymogen
    D Pei
    Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109 0640, USA
    Nature 375:244-7. 1995
    ..which is encrypted with an Arg-X-Arg-X-Lys-Arg recognition motif for the Golgi-associated proteinase, furin, a mammalian homologue of the yeast Kex2 pheromone convertase...
  44. pmc Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer
    Neil Senzer
    Mary Crowley Cancer Research Centers, Dallas, Texas 75201, USA
    Mol Ther 20:679-86. 2012
    ..colony-stimulating factor (GMCSF) and a novel bifunctional short hairpin RNAi (bi-shRNAi) targeting furin convertase, thereby downregulating endogenous immunosuppressive transforming growth factors (TGF) β1 and β2...
  45. pmc Cleavage targets and the D-arginine-based inhibitors of the West Nile virus NS3 processing proteinase
    Sergey A Shiryaev
    The Burnham Institute, La Jolla, CA 92037, USA
    Biochem J 393:503-11. 2006
    ..We have determined that the NS3 proteinase functions in a manner that is distantly similar to furin in cleaving the peptide and protein substrates...
  46. pmc Mutation of the f-protein cleavage site of avian paramyxovirus type 7 results in furin cleavage, fusion promotion, and increased replication in vitro but not increased replication, tissue tropism, or virulence in chickens
    Sa Xiao
    Virginia Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA
    J Virol 86:3828-38. 2012
    ..Syncytium formation and virus yield of the Fcs-5B virus was impaired by the furin inhibitor decanoyl-RVKR-CMK, whereas parental APMV-7 was not affected...
  47. ncbi Furin-like proprotein convertases are central regulators of the membrane type matrix metalloproteinase-pro-matrix metalloproteinase-2 proteolytic cascade in atherosclerosis
    Philipp Stawowy
    Department of Medicine Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D 13353 Berlin, Germany
    Circulation 111:2820-7. 2005
    ..This type of activation typically requires suitable furin-like proprotein convertases (PCs), specifically furin and PC5...
  48. pmc Furin processing of semaphorin 3F determines its anti-angiogenic activity by regulating direct binding and competition for neuropilin
    Matthew W Parker
    Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, Kentucky 40536, USA
    Biochemistry 49:4068-75. 2010
    ..Semaphorin 3F (Sema3F) possesses an RXRR furin recognition site in its C-terminus, and we demonstrate that it is proteolytically processed...
  49. ncbi The endoproteinase furin contains two essential Ca2+ ions stabilizing its N-terminus and the unique S1 specificity pocket
    Manuel E Than
    Max Planck Institut fur Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Acta Crystallogr D Biol Crystallogr 61:505-12. 2005
    The mammalian prohormone/proprotein convertase (PC) furin is responsible for the maturation of a great variety of homeostatic but also many pathogenic proteins within the secretory pathway and the endosomal pathway and at the cell ..
  50. ncbi Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases
    Alexander G Semenov
    HyTest Ltd, Turku, Finland
    Clin Chem 56:1166-76. 2010
    ..We investigated the role of 2 candidate convertases, furin and corin, in human proBNP processing.
  51. pmc Proteolytic processing of human cytomegalovirus glycoprotein B is dispensable for viral growth in culture
    Tanja Strive
    Institut für Virologie der Philipps Universität, 35037 Marburg, Germany
    J Virol 76:1252-64. 2002
    ..we report on the construction of a viral mutant in which the recognition site of gB for the cellular endoprotease furin was destroyed...
  52. ncbi Regulation of matrix metalloproteinase MT1-MMP/MMP-2 in cardiac fibroblasts by TGF-beta1 involves furin-convertase
    Philipp Stawowy
    Department of Medicine Cardiology, Deutsches Herzzentrum Berlin, D 13353 Berlin, Germany
    Cardiovasc Res 63:87-97. 2004
    ..b>Furin, a subtilisin/kexin-like proprotein convertase (PC), activates TGF-beta1 and membrane-bound MT1-MMP, which ..
  53. ncbi 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
    ..We demonstrated that the conversion of MT3-MMP zymogen into active form is dependent on both the furin-type convertase activity and the R(116)RKR motif...
  54. ncbi p38 kinase is crucial for osteopontin-induced furin expression that supports cervical cancer progression
    Vinit Kumar
    National Center for Cell Science, Pune, India
    Cancer Res 70:10381-91. 2010
    ..OPN regulates CD44-mediated p38 phosphorylation that induces NF-κB activation and NF-κB-dependent expression of furin, an extracellular protease implicated in human papilloma virus (HPV) processing that enhances cervical cancer cell ..
  55. ncbi Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is activated by the endoprotease furin
    Hung Do
    Novazyme Pharmaceuticals, Incorporated, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 277:29737-44. 2002
    ..Here we show that UCE is synthesized as an inactive proenzyme that is activated by the endoprotease furin, which cleaves an RARLPR/D sequence to release a 24-amino acid propiece...
  56. pmc Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo
    Miroslav S Sarac
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    Infect Immun 72:602-5. 2004
    The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease...
  57. pmc 2A peptide-based, lentivirus-mediated anti-death receptor 5 chimeric antibody expression prevents tumor growth in nude mice
    Meng Li
    Department of Biochemistry and Molecular Biology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Mol Ther 20:46-53. 2012
    ..of a lentivirus vector constructed by linking the heavy chain and the light chain of the antibody with a 2A/furin self-processing peptide in a single open reading frame that expresses a novel chimeric antibody (named as ..
  58. ncbi Expression and localization of MT1-MMP and furin in the glomerular wall of short- and long-term diabetic rats
    E Boucher
    Department of Pathology and Cell Biology, University of Montreal, Montreal, Quebec, Canada
    Kidney Int 69:1570-7. 2006
    ..to trace the expression and localization of membrane type-1 metalloprotease (MT1-MMP) and its activating enzyme furin, key proteins involved in basement membrane turnover, in short- and long-term diabetic rat renal tissues...
  59. ncbi Differential processing of proenkephalin by prohormone convertases 1(3) and 2 and furin
    M B Breslin
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112
    J Biol Chem 268:27084-93. 1993
    Recombinant vaccinia virus vectors were used to coexpress mouse prohormone convertase 1 (mPC1), mPC2, or human furin together with human proenkephalin in GH4C1 cells (rat pituitary somatomammotrophs) to examine the proteolytic processing ..
  60. pmc The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain
    Eric N Hampton
    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 104:14604-9. 2007
    ..This three-dimensional homology provides insight into the function of PCSK9 at the molecular level and will help to dissect the link between PCSK9 and CHD...
  61. ncbi Proprotein convertase furin enhances survival and migration of vascular smooth muscle cells via processing of pro-nerve growth factor
    Daniel Urban
    Department of Medicine Cardiology, Deutsches Herzzentrum Berlin, Germany
    J Biochem 153:197-207. 2013
    ..cells requires endoproteolytic processing of the precursor protein proNGF to β-NGF by the proprotein convertase furin. Pro- and β-NGF elicit opposite biological functions by differential neurotrophin-receptor binding, leading to ..
  62. ncbi An antibody delivery system for regulated expression of therapeutic levels of monoclonal antibodies in vivo
    Jianmin Fang
    Department of Preclinical Oncology and Immunology, Cell Genesys, Inc, South San Francisco, California 94080, USA
    Mol Ther 15:1153-9. 2007
    ..that drives expression of the antibody heavy and light chains linked by a 2A self-processing peptide and a furin cleavage site...
  63. pmc Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics
    Gero L Becker
    Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, D 35032 Marburg, Germany
    J Med Chem 53:1067-75. 2010
    b>Furin belongs to the family of proprotein convertases (PCs) and is involved in numerous normal physiological and pathogenic processes, such as viral propagation, bacterial toxin activation, cancer, and metastasis...
  64. pmc Ovarian furin (proprotein convertase subtilisin/kexin type3): expression, localization, and potential role in ovulation in the rat
    Brian P Kelty
    Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
    Biol Reprod 83:147-54. 2010
    The process of ovulation involves weakening of the follicular wall by proteolytic enzymes. The function of FURIN (also known as PCSK3) is to activate various proteolytic enzymes...
  65. ncbi Distinct roles of myosin Va in membrane remodeling and exocytosis of secretory granules
    Tanja Kogel
    Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen, Norway
    Traffic 11:637-50. 2010
    ..Interference with myosin Va function blocked the removal of the transmembrane protein furin from maturing SGs without affecting condensation and processing of proteins of the SG lumen...
  66. ncbi Upregulatory expression of furin and transforming growth factor-beta by fluid shear stress in vascular endothelial cells
    M Negishi
    Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
    Arterioscler Thromb Vasc Biol 21:785-90. 2001
    b>Furin, a yeast Kex2-family endoprotease, converts many vasoregulatory propeptides, including pro-transforming growth factor (TGF)-beta to their mature forms...
  67. ncbi Human testicular orphan receptor 4 enhances thyroid hormone receptor signaling
    Ya Hui Huang
    Department of Biochemistry, School of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China
    J Cell Physiol 222:347-56. 2010
    ..The interaction between TR4 and TR may enhance regulation of genes targeted by TR, such as furin, fibrinogen, cdk2 and p21 expression...
  68. ncbi Involvement of furin-like proprotein convertases in the arterial response to injury
    Joost P G Sluijter
    Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
    Cardiovasc Res 68:136-43. 2005
    b>Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to ..
  69. pmc Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins
    James M Binley
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Virol 76:2606-16. 2002
    ..In contrast, a soluble form of furin was specific for the gp120-gp41 cleavage site but cleaved inefficiently...
  70. ncbi The proprotein convertase furin colocalizes with caveolin-1 in the Golgi apparatus and endosomes of hepatocytes
    Gaetan Mayer
    Departement de pathologie et biologie cellulaire, Universite de Montreal, PO Box 6128, Montreal, Quebec, H3C 3J7, Canada
    Cell Tissue Res 316:55-63. 2004
    The significance of furin in the maturation and activation of a wide array of proproteins in the secretory pathway has been well demonstrated...
  71. pmc Loss-of-function point mutations and two-furin domain derivatives provide insights about R-spondin2 structure and function
    Sheng Jian Li
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, 37 Convent Drive, Bethesda, MD 20892, USA
    Cell Signal 21:916-25. 2009
    ..Cysteine assignments in a Rspo2 derivative containing only the two furin-like domains (Rspo2-2F) provided the first information about the disulfide bonding pattern of this motif, which ..
  72. pmc Human monoclonal antibodies generated following vaccination with AVA provide neutralization by blocking furin cleavage but not by preventing oligomerization
    Kenneth Smith
    Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
    Vaccine 30:4276-83. 2012
    ..We demonstrate that hmAb p6C01 is neutralizing by preventing furin cleavage of PA in a dose-dependent manner, but the mechanism of p6F01 is unclear...
  73. ncbi SKI-1 and Furin generate multiple RGMa fragments that regulate axonal growth
    Nardos G Tassew
    Genetics and Development Division, Toronto Western Research Institute, MCL 6 415, 399 Bathurst Street, Toronto M5T 2S8, Ontario, Canada
    Dev Cell 22:391-402. 2012
    ..Here, we show that Furin and SKI-1 combine with autocatalytic cleavage and a disulfide bridge to generate four membrane-bound and three ..
  74. pmc Tumour growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin 3E isoform
    Andrea Casazza
    Institute for Cancer Research and Treatment IRCC, University of Torino Medical School, Candiolo, Italy
    EMBO Mol Med 4:234-50. 2012
    ..In summary, we conclude that Uncl-Sema3E is a novel inhibitor of tumour angiogenesis and growth that concomitantly hampers metastatic spreading...
  75. pmc Differential modulation of prM cleavage, extracellular particle distribution, and virus infectivity by conserved residues at nonfurin consensus positions of the dengue virus pr-M junction
    Jiraphan Junjhon
    Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
    J Virol 82:10776-91. 2008
    In the generation of flavivirus particles, an internal cleavage of the envelope glycoprotein prM by furin is required for the acquisition of infectivity...
  76. ncbi Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein
    Simona Ozden
    Unité d Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 3015, Institut Pasteur, 75724 Paris, France
    J Biol Chem 283:21899-908. 2008
    ..We show that among a large panel of proprotein convertases, membranous furin but also PC5B can process E3E2 from African CHIKV strains at the HRQRR(64) / ST site, whereas a CHIKV strain of ..
  77. ncbi Cleavage mechanism of the H5N1 hemagglutinin by trypsin and furin
    X L Guo
    College of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
    Amino Acids 35:375-82. 2008
    ..e., trypsin and furin and peptides of the cleavage sites specific to H5N1 and H1 HAs, which constitute models of HA precursor in complex ..
  78. pmc Mutagenesis of varicella-zoster virus glycoprotein B: putative fusion loop residues are essential for viral replication, and the furin cleavage motif contributes to pathogenesis in skin tissue in vivo
    Stefan L Oliver
    Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
    J Virol 83:7495-506. 2009
    ..In contrast to HSV gB, VZV gB had a furin recognition motif ([R]-X-[KR]-R-|-X, where | indicates the position at which the polypeptide is cleaved) at ..
  79. pmc MicroRNA-24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN
    Coralia Luna
    Department of Ophthalmology, Duke University, Durham, North Carolina 27710, USA
    J Cell Physiol 226:1407-14. 2011
    ..CMS induced the expression of miR-24 that led to the down regulation of the subtilisin-like proprotein convertase FURIN, which is known to play a major role in the processing of TGFβ1...
  80. pmc Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface
    S S Molloy
    Vollum Institute, Portland, OR
    EMBO J 13:18-33. 1994
    b>Furin is a membrane-associated endoprotease that efficiently cleaves precursor proteins on the C-terminal side of the consensus sequence, Arg-X-Lys/Arg-Arg1, and has been proposed to catalyze these reactions in both exocytic and ..
  81. pmc Site-specific cleavage of BMP4 by furin, PC6, and PC7
    Sylvia M Nelsen
    Department of Molecular and Medical Genetics, Oregon Health and Science University School of Medicine, Portland, Oregon 97239 3098, USA
    J Biol Chem 284:27157-66. 2009
    ..In Xenopus oocytes, furin and PC6 function redundantly to cleave both the S1 and S2 sites of pro-BMP4, as evidenced by the results of ..
  82. ncbi Regulation of cell survival by secreted proneurotrophins
    R Lee
    Division of Hematology, Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Science 294:1945-8. 2001
    ..The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR to mediate apoptosis and mature forms activating Trk receptors to promote survival...
  83. ncbi Furin is an endogenous regulator of alpha-secretase associated APP processing
    Eun Mi Hwang
    Department of Physiology, Institute of Health Science, Gyeongsang National University College of Medicine, Jinju, Republic of Korea
    Biochem Biophys Res Commun 349:654-9. 2006
    ..Here, we examined putative role of furin in the regulation of alpha-secretase activity in vitro and in vivo...
  84. ncbi Functional characterization of the human placental fusogenic membrane protein syncytin 2
    Chie Pein Chen
    Division of High Risk Pregnancy and Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan
    Biol Reprod 79:815-23. 2008
    ..The endoprotease furin was found to be involved in the posttranslational cleavage of syncytin 1 and 2 polypeptides into surface and ..
  85. pmc Cleavage inhibition of the murine coronavirus spike protein by a furin-like enzyme affects cell-cell but not virus-cell fusion
    Cornelis A M de Haan
    Virology Division, Department of Infectious Diseases and Immunology, Yalelaan 1, 3584CL Utrecht, The Netherlands
    J Virol 78:6048-54. 2004
    ..mouse hepatitis coronavirus strain A59 spike protein was blocked in a concentration-dependent manner by a peptide furin inhibitor, indicating that furin or a furin-like enzyme is responsible for this process...
  86. pmc Cleavage of group 1 coronavirus spike proteins: how furin cleavage is traded off against heparan sulfate binding upon cell culture adaptation
    C A M de Haan
    Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medcine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands
    J Virol 82:6078-83. 2008
    ..Here, however, we show that some group 1 coronavirus spike proteins carry a furin enzyme recognition motif and can actually be cleaved, as demonstrated for a feline coronavirus...
  87. ncbi Proprotein convertase models based on the crystal structures of furin and kexin: explanation of their specificity
    Stefan Henrich
    Max Planck Institut fur Biochemie, Abteilung für Strukturforschung, Am Klopferspitz 18, 82152 Martinsried, Germany
    J Mol Biol 345:211-27. 2005
    ..The recently published crystal structures of the soluble mouse furin and yeast kexin ectodomains have revealed the relative arrangement of catalytic and P domains, the exact domain ..
  88. ncbi The serpin proteinase inhibitor 8: an endogenous furin inhibitor released from human platelets
    Julie Leblond
    Immunology Division, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4
    Thromb Haemost 95:243-52. 2006
    ..We have previously identified the serine protease furin as a platelet-derived enzyme with an intrinsic role in platelet functions...
  89. pmc Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection
    Rebecca M Richards
    Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 103:1522-7. 2006
    ..that this step depends on the site-specific enzymatic cleavage of the PV minor virion protein L2 at a consensus furin recognition site...
  90. pmc The furin protease cleavage recognition sequence of Sindbis virus PE2 can mediate virion attachment to cell surface heparan sulfate
    W B Klimstra
    Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7290, USA
    J Virol 73:6299-306. 1999
    ..in HS-dependent attachment to cells and efficient attachment to heparin-agarose beads, presumably because the furin recognition site for PE2 cleavage also represents a candidate HS binding sequence...
  91. pmc Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin
    W Schafer
    Institut fur Virologie, Philipps Universitat Marburg, Germany
    EMBO J 14:2424-35. 1995
    b>Furin, a subtilisin-like eukaryotic endoprotease, is responsible for proteolytic cleavage of cellular and viral proteins transported via the constitutive secretory pathway...
  92. pmc Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2
    Wendy R Gordon
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 4:e6613. 2009
    Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits...
  93. ncbi Furin interacts with proMT1-MMP and integrin alphaV at specialized domains of renal cell plasma membrane
    Gaetan Mayer
    Department of Pathology and Cell Biology, Universite de Montreal, Montreal, Quebec, H3C 3J7, Canada
    J Cell Sci 116:1763-73. 2003
    ..Both membrane type-1 MMP (MT1-MMP) and the integrin alphaV subunit are fully activated upon cleavage at a furin recognition site...
  94. pmc Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins
    K Nakayama
    Institute of Biological Sciences and Gene Experiment Center, University of Tsukuba, Tsukuba Science City, Ibaraki 305, Japan
    Biochem J 327:625-35. 1997
    ..Seven distinct proprotein convertases of this family (furin, PC2, PC1/PC3, PC4, PACE4, PC5/PC6, LPC/PC7/PC8/SPC7) have been identified in mammalian species, some having ..
  95. ncbi Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins
    Stephanie McMahon
    Immunology Division, Pulmonary Division, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec
    J Biol Chem 280:6561-9. 2005
    ..many angiogenic and invasion-related mediators, some of which are natural substrates for the proprotein convertase furin. Analysis of furin promoters revealed the presence of putative binding sites for hypoxia-inducible factor-1 (HIF-1)..
  96. pmc The Spn4 gene of Drosophila encodes a potent furin-directed secretory pathway serpin
    Martin J Richer
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Proc Natl Acad Sci U S A 101:10560-5. 2004
    ..secretory pathway serine protease inhibitor (serpin) from Drosophila melanogaster that contains a consensus furin cleavage site, -Arg(P4)-Arg-Lys-Arg(P1) downsream-, in its reactive site loop (RSL)...
  97. pmc In vivo evidence that furin from hepatocytes inactivates PCSK9
    Rachid Essalmani
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 286:4257-63. 2011
    ..Ex vivo data showed that human PCSK9 is inactivated by cleavage at Arg(218)↓ by the overexpressed convertases furin and PC5/6A...
  98. ncbi The crystal structure of the proprotein processing proteinase furin explains its stringent specificity
    Stefan Henrich
    Max Planck Institut fur Biochemie, Abt Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Nat Struct Biol 10:520-6. 2003
    ..b>Furin, the best-characterized member of the mammalian PC family, has essential functions in embryogenesis and ..
  99. ncbi Simultaneous expression of furin and vascular endothelial growth factor in human oral tongue squamous cell carcinoma progression
    Ricardo Lopez De Cicco
    Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 10:4480-8. 2004
    Squamous cell carcinoma (SCC) of the tongue is a common malignancy of the oral cavity. Furin convertase activates several precursor matrix metalloproteinases involved in the degradation of the extracellular matrix...
  100. ncbi Furin cleavage of the respiratory syncytial virus fusion protein is not a requirement for its transport to the surface of virus-infected cells
    R J Sugrue
    MRC Virology Unit, Institute of Virology, Church Street, G11 5JR, Glasgow, UK
    J Gen Virol 82:1375-86. 2001
    The intracellular cleavage of respiratory syncytial virus (RSV) fusion (F) protein by furin was examined...
  101. pmc Role of cytoplasmic domain serines in intracellular trafficking of furin
    Florencia B Schapiro
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Biol Cell 15:2884-94. 2004
    b>Furin is a transmembrane protein that cycles between the plasma membrane, endosomes, and the trans-Golgi network, maintaining a predominant distribution in the latter...

Research Grants62

  1. Development and testing of polyvalent anthrax toxin inhibitors
    JEREMY S MOGRIDGE; Fiscal Year: 2012
    ..Protective antigen (PA) binds cellular receptors and is cleaved by furin-like proteases, which leads to the heptamerization of the cell-associated PA63 fragment...
  2. Receptor-mediated Endocytosis-Mechanism and Function
    Frederick R Maxfield; Fiscal Year: 2013
    ..g., labeled Tac-Furin, Tac-TGN38, CI-MPR) within minutes after inactivation...
  3. Modulation of the Epithelial Sodium Channel by Proteases and Peptide Inhibitors
    CHRISTOPHER JOHN PASSERO; Fiscal Year: 2010
    ..The other pool avoids maturation and remains inactive. During maturation, the serine proteases furin and prostasin cleave inhibitory residues from the alpha and gamma subunits of ENaC, activating the channel...
  4. Genetic Determinants of Hypertensive Heart Disease in CRI
    Daniel L Dries; Fiscal Year: 2011
    ..The candidate genes of interest are: corin, furin, ANP, BNP, CNP, NPR-A, NPR-B, NPR-C, PKG-I, and NEP...
  5. Spatial Regulation of BMP Signaling in Dorsoventral Patterning
    David A Weisblat; Fiscal Year: 2013
    ..between two different cell types in the embryo reflects differences in the processing of BMP pro-peptides by Furin or other members of the pro- peptide convertase subtilisin/kexin (PCSK) family of proteases, which normally ..
  6. Physiologic role of the gamma epithelial sodium channel subunit in the kidney
    Donald E Kohan; Fiscal Year: 2010
    ..In particular, cleavage at defined sites of the extracellular domain of the ? subunit by the proteases furin and prostasin has a key role in activating ENaC in heterologous systems, presumably by releasing an inhibitory ..
  7. Posttranslational regulation of augurin, a new secretory tumor suppressor
    Akihiko Ozawa; Fiscal Year: 2013
    ..that two specific proaugurin-derived peptides are generated by the action of the specific proprotein convertase furin in vitro. Furthermore, we have found that proaugurin is sulfated during trafficking through the secretory pathway...
  8. IgA Protease as Therapy to Reverse IgA Nephropathy
    Jiazhou Qiu; Fiscal Year: 2012
    ..Phase I we will use the recent structure information to introduce two mutational insertions that can be cleaved by furin, a specific enzyme that is intended to reduce the IgA protease size without modifying its function...
  9. Countermeasures for Bioterroism Targeting Cellular Host Factors
    John C Reed; Fiscal Year: 2012
    ..To become active, Protective Antigen (PA), an essential delivery component of lethal Anthrax Toxin, requires furin-family proteases for proteolytic processing, similar to several additional bacterial virulence factors and viruses,..
  10. Identification of novel mammalian genes required for intoxication by antrax toxin
    G Jilani Chaudry; Fiscal Year: 2012
    ..Toxin entry into cells comprises multiple steps: PA binds receptors, furin cleaves off a portion of PA, bound PA forms a heptamer, EF and LF bind the heptamer, the whole complex is ..
  11. Von Willebrand Factor Multimer Assembly and Structure
    J Evan Sadler; Fiscal Year: 2012
    ..The cleavage of the VWF propeptide by furin also is regulated by pH, and the role of propeptide cleavage in VWF storage and secretion will be characterized...
  12. MOLECULAR ANALYSIS OF ALPHAVIRUS MEMBRANE FUSION PROTEIN
    Margaret Kielian; Fiscal Year: 2013
    ..Late in the secretory pathway the companion proteins are proteolytically processed by cellular furin, thereby priming the dimer to dissociate a low pH during virus entry...
  13. A Multidisciplinary Analysis of Gelsolin Amyloid Disease
    Jeffery W Kelly; Fiscal Year: 2010
    ..mutations prevent Ca2+ binding to domain 2, rendering plasma gelsolin susceptible to aberrant endoproteolysis by furin in the Golgi during secretion...
  14. Priming and fusion activation of the SARS coronavirus spike glycoprotein
    Gary R Whittaker; Fiscal Year: 2010
    ..Mutation of basic residues in this region leads to a loss of trypsin-mediated fusion and the introduction of a furin recognition site in this position allows fusion in the absence of ACE2 (the SARS-CoV receptor) suggesting an ..
  15. OPIOID PEPTIDE SYNTHESIZING ENZYMES
    Iris Lindberg; Fiscal Year: 2013
    ..with Wolfram Bode and Manuel Than, we obtained the first crystal structure of a related family member, furin. Our long-standing collaboration with the Torrey Pines Institute for Molecular Studies has identified potent furin ..
  16. Furin and the Etiopathogenesis of UV-Induced Skin Cancer
    Andres J Klein-Szanto; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Furin is a protein processing enzyme of the family of proprotein convertases (PCs), which has a significant role in cancer etiopathogenesis...
  17. Structural and Functional Studies of Invertebrate Classical Cadherins
    Melissa A Walker; Fiscal Year: 2010
    ..Like vertebrate cadherins, DN-cadherin may require proteolytic processing by a furin-like protease to achieve its mature form...
  18. Identification of short functional motifs as potential drug targets for HIV
    Martin Schiller; Fiscal Year: 2009
    ..consensus motif (Arg-x-Lys/Arg-Arg;[unreadable]x[unreadable]is any residue) for cleavage by the host protease, Furin. One of the major limitations in identifying short functional motifs is the lack of a systematic approach and ..
  19. SPLUNC1-Derived Peptides as ENaC Antagonists
    Robert Tarran; Fiscal Year: 2013
    ..applicant): The extracellular loops of [unreadable] and ? ENaC can be roteolytically cleaved at multiple sites by furin-type convertases, serine proteases and neutrophil elastase, leading to activation of the channel and increased Na+ ..
  20. Determinants of organelle-specific activation of Proprotein Convertase 1
    DANIELLE MARIE WILLIAMSON; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Proprotein convertases (PCs), such as PC1 and furin, are a ubiquitous super-family of evolutionarily conserved serine proteases responsible for mediating a diverse range of processing steps to ..
  21. Identification of small molecule furin-like protease inhibitors
    JULIA COPPOLA; Fiscal Year: 2009
    ..of this proposal is to develop a non-invasive, real-time, quantifiable cell-based assay to detect and report on furin-like protease activity to identify small molecule inhibitors of furin-like proteases by high throughput screening (..
  22. GENE THERAPY AND SEIZURES
    Thomas J McCown; Fiscal Year: 2011
    ..To further optimize the anti-seizure efficacy, studies will determine if the inclusion of a furin cleavage site supports the expression and secretion of two or more gene products from a single AAV vector, thus ..
  23. Biochemistry of MT1-MMP activation in malignancy
    Alex Y Strongin; Fiscal Year: 2013
    ..prodomain while in normal cells MT1- MMP activity is controlled by the intact prodomain that is released by furin cleavage alone...
  24. PTHRP 1 to 173 IN CHONDROCYTES
    Robert Terkeltaub; Fiscal Year: 2005
    ..In doing so, we will test the hypothesis that furin-like subtilisin family proprotein convertases (PCs) are at least partially responsible...
  25. Molecular Requirements for Recombinant Cytotoxins Efficacy
    Waldemar Debinski; Fiscal Year: 2010
    ..of the restricted binding sites for the cytotoxins and an intracellular protease activating bacterial toxins (furin) play major roles in the cytotoxins'tumor cell killing...
  26. Guidance of Taste Nerve During Development
    MICHAEL ROCHLIN; Fiscal Year: 2003
    ..The role of the protease furin, previously implicated in Sema3A inactivation, will be tested in vitro using a specific inhibitor.
  27. Blockade of Anthrax Cytotoxicity Using Furin Inhibitors
    Iris Lindberg; Fiscal Year: 2003
    ..Previous research has shown that this cleavage is performed by a cellular surface enzyme known as furin, a member of the family of eukaryotic subtilisins...
  28. Intracellular Actions of the Lymphangiogenic Growth Factor VEGF-D in Fibroblasts
    Souheil El-Chemaly; Fiscal Year: 2013
    ..As VEGF-D processing is known to result from actions of furin and protein conve^rtase (PC)-5, manipulation of VEGF-D processing might produce desirable therapeutic effects on ..
  29. Specificity and Structure: The Kex 2 and Furin Proteases
    Robert Fuller; Fiscal Year: 2005
    ..The first known human Kex2 homologue, furin, is implicated in maturation of growth factors and growth factor receptors, coagulation factors, viral ..
  30. STUDIES ON CLOSTRIDIUM SEPTICUM LETHAL TOXIN
    Rodney Tweten; Fiscal Year: 2003
    ..is produced as an inactive protoxin which requires proteolytic activation by normal cellular proteases such as furin. The investigators propose to continue the detailed study of the cytolytic mechanism of alpha toxin in order to ..
  31. Characterizing Class 1 Fusion Proteins: Elucidation of Coronavirus fusion peptide
    IKENNA MADU; Fiscal Year: 2009
    ..A bioinformatics analysis of the IBV Bdtte spike protein revealed a unique consensus Furin cleavage site within the S2 domain of the spike protein...
  32. Specificity of Subtilisin-like Proprotein Convertases
    JOSEPH SUCIC; Fiscal Year: 2003
    ..The goal of this project is to investigate the substrate specificity of four widely expressed SPCs designated furin, PACE4, PCS, and PC7, each of which has unique substrate preferences...
  33. BIOSYNTHESIS OF BLOOD CLOTTING PROTEINS
    Bruce Furie; Fiscal Year: 2001
    ..The physiological roles of furin and proprotein convertase 7 (PC7) in propeptide cleavage of the vitamin K-dependent proteins will be determined ..
  34. B LYMPHOCYTES--DIFFERENTIATION AND TRIGGERING
    Brigitte Huber; Fiscal Year: 2003
    ..Many retroviral proteins, including HIV-1 gp160 and MMTV env, require processing by furin to be functional...
  35. GOLGI TARGETING AND RETENTION OF YEAST KEX2 PROTEASE
    Robert Fuller; Fiscal Year: 2009
    ..These transport pathways localize processing enzymes (e.g. Kex2 protease and furin) to their sites of action, effect lysosomal/vacuolar biogenesis and regulate levels of plasma membrane ..
  36. MOLECULAR BASIS OF PHENOTYPE OF FBN1/FBN2 MUTATIONS
    Dianna Milewicz; Fiscal Year: 2000
    ..thereafter, 140 residues of the carboxyl-terminal fragment are removed by a protease that is a member of the PACE (furin) family...
  37. Proteolytic cleavage of the Hendra virus fusion protein
    REBECCA DUTCH; Fiscal Year: 2006
    ..It is clear that the cellular secretory protease furin, known to cleave other paramxyovirus F proteins, is not involved in proteolytic activation of the Hendra F protein...
  38. NONREPLICATING MODIFIED VIRUS LIKE PARTICLES (VLPS) VAC
    Polly Roy; Fiscal Year: 1999
    ..To generate the mature form of gp120/gp41 from the precursor gp160, a cleavage protease, furin, will be provided in trans in insect cells which lack this enzyme...
  39. Identification of Small Molecule Inhibitors of Furin
    NORA GREEN; Fiscal Year: 2003
    Recent experimental findings by the Kelly and Balch groups indicate that the proprotein convertase furin is responsible for the first proteolytic cleavage event in the DI 87N and DI 87Y mutants of gelsolin...
  40. MAGE-A3/HPV 16 Peptide Vaccines for Head and Neck Cancer
    Scott Strome; Fiscal Year: 2006
    ..to therapeutic peptide vaccines using Trojan complexes, composed of CD4 and CD8 T cell epitopes, connected by furin cleavable linkers...
  41. Hexa-D-Arg: A Furin Inhibitor for Anthrax Biodefense
    Prasad Sunkara; Fiscal Year: 2004
    ..cleavage of the anthrax toxin-PA (protective antigen) residue by a ubiquitously expressed mammalian cell protease furin, such that it now is able to form a multimeric complex (pore) that enables entry of the LF (lethal factor) and EF (..
  42. Furin Inhibition in HIV Disease
    Seth Pincus; Fiscal Year: 2006
    ..envelope glycoprotein precursor, gpl60, is cleaved into the mature forms, gp120 and gp41, by the cellular protease furin and furin-like proprotein convertases (PPCs)...
  43. A transmembrane collagen induced in prostate cancer
    Bruce Zetter; Fiscal Year: 2007
    ..its transmembrane domain or as a soluble form generated by cleavage of the ectodomain form the cell surface via furin protease activity...
  44. Developing a mouse model to study Notch furin processing
    GERALDINE WEINMASTER; Fiscal Year: 2002
    ..following ligand binding to a heterodimeric form of Notch that is generated through proteolytic processing by furin. In addition to CSL-dependent Notch signaling we have identified another pathway that functions independently of ..
  45. Molecular Basis for Ebola Virus Pathogenicity
    Yoshihiro Kawaoka; Fiscal Year: 2007
    ..Moreover, using a wild-type Ebola virus, furin-mediated GP cleavage, or the mucin-like domain in GP, and the secreted glycoprotein, sGP, will also be evaluated ..
  46. Analysis of BMP-4 activity in Cleavage mutant mice
    Jan Christian; Fiscal Year: 2007
    ..ProBMP-4 is initially cleaved at a consensus furin motif adjacent to the mature ligand domain and this allows for subsequent cleavage at an upstream nonconsensus ..
  47. Role of Sortlin in regulating proteolytic activation of BMP4 during embryogenesis
    Jan Christian; Fiscal Year: 2009
    ..BMP4 is generated as a latent precursor, which is cleaved by furin to generate an active ligand...
  48. HUMAN FURIN PROCESSING ENDOPROTEASE
    Gary Thomas; Fiscal Year: 2000
    DESCRIPTION: Furin is a membrane-localized endoprotease that cleaves a number of biologically important molecules as part of their normal biosynthesis and processing...
  49. A NOVEL TYPE II TRANSMEMBRANE MATRIX METALLOPROTEINASE
    Duanqing Pei; Fiscal Year: 2000
    ..and displayed on cell membrane as a type II membrane proteinase, converted into soluble and active form by furin in the transGolgi network, and utilized by cells to degrade protein substrates as specified by its Cys-array (CA) ..
  50. Proprotein Processing, Trafficking and Secretion Gordon Conference
    Nabil Seidah; Fiscal Year: 2006
    ..The integration of protease systems that are required both for normal physiology and human disease will be relevant to our understanding of the molecular bases of diabetes, cancer, Alzheimer's and drug addiction. ..
  51. Role of Inter-alpha Inhibitors in Anthrax Intoxication
    Steven Opal; Fiscal Year: 2007
    ..We have obtained evidence that lalp inhibit furin, a key enzyme that activates PA by removing a small 20 kDa fragment at the N-terminal yielding the active subunit ..
  52. Modified Envelope Glycoproteins for HIV-1 Vaccine
    John P Moore; Fiscal Year: 2010
    ..11/07) Page 2 Form Page 2 ..
  53. GRSA Proteins in the Diagnosis of Breast Cancer
    WILLIAM NORTH; Fiscal Year: 2002
    ..These methods could be applicable to all patients with breast cancer or suspected breast cancer. ..
  54. BABAA RECEPTORS IN AGING & ALZHEIMER'S DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  55. BAG-75: UNIQUE MARKER OF PRIMARY BONE FORMATION
    JEFFREY GORSKI; Fiscal Year: 2003
    ..Stimulation of appositional formation by lamellar bone would not be expected to have the same effect. These future functional studies require determination of the BAG-75 cDNA sequence. ..
  56. MECHANISMS OF MAMMALIAN FERTILIZATION
    PAUL WASSARMAN; Fiscal Year: 2007
    ..Furthermore, the research could have important consequences for development of novel reversible contraceptive methods that prevent ZP formation during oogenesis in humans. ..
  57. Structure-based Drug Design for Smallpox Therapy
    Alex Strongin; Fiscal Year: 2008
    ..When appropriate benchmarks are met, the drug candidates will be delivered to the government for continued testing and refinement involving the variola virus. [unreadable] [unreadable]..
  58. CHARACTERIZING THE MECHANISMS OF ALSV ENTRY INTO CELLS
    John Young; Fiscal Year: 2004
    ..Understanding this process in detail should lead to better antiviral therapeutic strategies and aid with viral targeting approaches for gene therapy protocols. ..
  59. Targeting the PEX Domain of MT1-MMP: Novel Cancer Therapy
    Jian Cao; Fiscal Year: 2010
    ..I propose that the current project will help us to better understand cancer progression and lead to the development of novel basic tools for treatment of early stage cancer. ..
  60. DDR1 controls tumor homing in breast to bone metastasis
    Celso Gomez Sanchez; Fiscal Year: 2004
    ..A survey of the CRISP database showed that the NIH currently funds no other research on DDR1. ..
  61. MECHANISMS OF CELL KILLING INDUCED BY RETROVIRUSES
    John Young; Fiscal Year: 2003
    ..The fifth aim studies a variant of ALV-A, the avian hemangioma virus, which induces cell-killing. These studies will identify the cell death pathway induced possibly through the TVA receptor. ..
  62. Role of HCMV Glycoprotein in Viral Biogenesis
    Gary Thomas; Fiscal Year: 2005
    ..2) TGN localization is mediated by interaction of gB with the cellular connector, PACS- 1, and 3) inhibition of furin-dependent cleavage of gB causes missorting of the unprocessed glycoprotein and is coupled with a dramatic block in ..