Pcsk1

Summary

Gene Symbol: Pcsk1
Description: proprotein convertase subtilisin/kexin type 1
Alias: Nec-1, Nec1, PC1, PC3, Phpp-1, SPC3, neuroendocrine convertase 1, NEC 1, furin homolog, prohormone convertase 1, prohormone convertase 1/3, propeptide-processing protease, proprotein convertase 1
Species: mouse

Top Publications

  1. pmc Pax6 directly down-regulates Pcsk1n expression thereby regulating PC1/3 dependent proinsulin processing
    Ting Liu
    Peking University Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
    PLoS ONE 7:e46934. 2012
  2. 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
  3. ncbi Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas
    Maria E Wilson
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0534, USA
    Mech Dev 115:171-6. 2002
  4. ncbi trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues
    L Tessarollo
    Molecular Embryology Section, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Maryland 21702 1201
    Development 118:463-75. 1993
  5. ncbi The new enzymology of precursor processing endoproteases
    D F Steiner
    Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637
    J Biol Chem 267:23435-8. 1992
  6. pmc Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology, University of Chicago, and the Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 99:10293-8. 2002
  7. ncbi Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas
    M Sander
    Hormone Research Institute, University of California San Francisco, San Francisco, CA 94143 0534, USA
    Development 127:5533-40. 2000
  8. ncbi Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides
    N G Seidah
    Laboratories of Biochemical and Molecular Neuroendocrinology and the Protein Engineering Network of Centres of Excellence, Clinical Research Institute of Montreal, Canada
    Brain Res 848:45-62. 1999
  9. ncbi Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells
    L Sussel
    Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143, USA
    Development 125:2213-21. 1998
  10. ncbi Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development
    Carly St Germain
    Diseases of Aging Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ontario, Canada
    Mol Reprod Dev 72:483-93. 2005

Research Grants

Scientific Experts

  • J F Rehfeld
  • R Chavez-Valdez
  • K Kageyama
  • M Mbikay
  • N G Seidah
  • Patricia M Vuguin
  • Donald F Steiner
  • Xiaorong Zhu
  • Jimmy D Dikeakos
  • Randi Ugleholdt
  • Nadia Rabah
  • Arunangsu Dey
  • Robert Day
  • Lydiane Funkelstein
  • Claude Lazure
  • Michel Chretien
  • Timothy L Reudelhuber
  • M Duhamel
  • Mouna Saidi
  • Yongjie Chen
  • Alison Miyamoto
  • Lloyd D Fricker
  • William C Wetsel
  • Roxane Desjardins
  • Sarah Refaie
  • Ting Liu
  • Daniel B Constam
  • Marcelo Y Icimoto
  • Jens J Holst
  • Simon Kordowich
  • Sandra Gagnon
  • Yoshiaki Tamura
  • Pedro L Herrera
  • Jonathan H Wardman
  • JieLi Lu
  • Daniel Mesnard
  • Ardalan Minokadeh
  • Aouatef Ait-Lounis
  • German Kilimnik
  • Akihiko Ozawa
  • Thomas Toneff
  • Christoph Peters
  • Anjali K Nath
  • Vivian Hook
  • Thomas Reinheckel
  • Jeffrey Gagnon
  • Christina Norrbom
  • Shin Rong Hwang
  • Anne Blanchard
  • Raymond Carroll
  • Dana L Fox
  • Philip A Seymour
  • Marie Josée Lacombe
  • Theodore C Friedman
  • Maike Sander
  • Shelley B Nelson
  • Rhonda D Wideman
  • Toshihiko Masui
  • Janice Mayne
  • R Day
  • Dany Gauthier
  • David J Lloyd
  • Iris Lindberg
  • Carly St Germain
  • D B Constam
  • Atira Hardiman
  • Hui Pan
  • B M Cain
  • Lucy Marzban
  • Luciane Lamotte
  • Gilles Croissandeau
  • Jeffrey Stein
  • H Gagnon
  • M Wisztorski
  • Natacha Bernard
  • F Rodet
  • A N Murgoci
  • I Fournier
  • L Sussel
  • Chunling Zhang
  • M Salzet
  • R Desjardins
  • M Vincent
  • R Winsky-Sommerer
  • Irina Arnaoutova
  • Patrick Kitabgi
  • Francis Beaudry
  • Alberto Orduna Ruiz
  • Soufiane Kamali
  • Michael A Tangrea

Detail Information

Publications91

  1. pmc Pax6 directly down-regulates Pcsk1n expression thereby regulating PC1/3 dependent proinsulin processing
    Ting Liu
    Peking University Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
    PLoS ONE 7:e46934. 2012
    ..Our previous study found that Pax6 deficiency caused down-expression of prohormone convertase 1/3 (Pcsk1), resulting in defective proinsulin processing...
  2. 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 ..
  3. ncbi Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas
    Maria E Wilson
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0534, USA
    Mech Dev 115:171-6. 2002
    ..We show here that these cells express islet amyloid polypeptide and prohormone convertase 1/3 (PC1/3), proteins that are not expressed by mature alpha cells, but are found in beta cells...
  4. ncbi trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues
    L Tessarollo
    Molecular Embryology Section, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Maryland 21702 1201
    Development 118:463-75. 1993
    ..Alignment with available chromosomal maps identify possible linkage between the Trk genes and known neurological mutations...
  5. ncbi The new enzymology of precursor processing endoproteases
    D F Steiner
    Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637
    J Biol Chem 267:23435-8. 1992
  6. pmc Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology, University of Chicago, and the Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 99:10293-8. 2002
    The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway...
  7. ncbi Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas
    M Sander
    Hormone Research Institute, University of California San Francisco, San Francisco, CA 94143 0534, USA
    Development 127:5533-40. 2000
    ..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation...
  8. ncbi Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides
    N G Seidah
    Laboratories of Biochemical and Molecular Neuroendocrinology and the Protein Engineering Network of Centres of Excellence, Clinical Research Institute of Montreal, Canada
    Brain Res 848:45-62. 1999
    ..Seven mammalian precursor convertases (PCs) have been identified: PC1, PC2, furin, PC4, PC5, PACE4 and PC7...
  9. ncbi Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells
    L Sussel
    Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143, USA
    Development 125:2213-21. 1998
    ..1. We propose that Nkx2.2 is required for the final differentiation of pancreatic beta cells, and in its absence, beta cells are trapped in an incompletely differentiated state...
  10. ncbi Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development
    Carly St Germain
    Diseases of Aging Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ontario, Canada
    Mol Reprod Dev 72:483-93. 2005
    ..b>Proprotein convertase 1 (PC1) expression was further examined at the protein level...
  11. ncbi PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism
    Jimmy D Dikeakos
    Laboratory of Molecular Biochemistry of Hypertension, Institut de recherches cliniques de Montreal IRCM, QC, Canada
    FEBS J 274:4094-102. 2007
    ..b>PC1/3, PC2 and PC5/6A are the only members of the PC family that are targeted to dense core secretory granules, where ..
  12. pmc SPC4, SPC6, and the novel protease SPC7 are coexpressed with bone morphogenetic proteins at distinct sites during embryogenesis
    D B Constam
    Harvard University, Department of Molecular and Cellular Biology, The Biological Laboratories, Cambridge, Massachusetts 02138, USA
    J Cell Biol 134:181-91. 1996
    ..A comparison of these expression patterns with those of several bone morphogenetic proteins (BMPs) indicates that processing of these growth factors may be limited by the local availability of SPCs...
  13. ncbi Purification and characterization of the prohormone convertase PC1(PC3)
    Y Zhou
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112
    J Biol Chem 268:5615-23. 1993
    The prohormone convertases PC1 (also known as PC3) and PC2 have been implicated in the biosynthesis of several polypeptide hormones and neuropeptides...
  14. pmc Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and P
    S Benjannet
    J A DeSève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    Biochem J 294:735-43. 1993
    We present herein the pulse-chase analysis of the biosynthesis of the prohormone convertases PC1 and PC2 in the endocrine GH4C1 cells infected with vaccinia virus recombinants expressing these convertases...
  15. ncbi Autoproteolytic activation of the mouse prohormone convertase mPC1
    L J Goodman
    Department of Cell Genetics, Genentech, Inc, South San Francisco, CA 94080
    Biochem Biophys Res Commun 201:795-804. 1994
    ..proregion processing of the active-site mutant could not be complemented by the overexpression of active furin or PC1. Additionally coexpression of a cleavage-site mutant (Arg110-Ala) with the substrate prorelaxin further ..
  16. ncbi Single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzyme
    Nadia Rabah
    Neuropeptides Structure and Metabolism, Institut de Recherches Cliniques de Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 281:7556-67. 2006
    The proprotein convertase PC1/3 is synthesized as a large precursor that undergoes proteolytic processing of the signal peptide, the propeptide and ultimately the COOH-terminal tail, to generate the mature form...
  17. pmc Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology and Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 99:10299-304. 2002
    ..Here we report that disruption of the expression of PC1/3 (SPC3) produces a much more severe block in proinsulin conversion...
  18. pmc Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases
    D B Constam
    Harvard University, Department of Molecular and Cellular Biology, Cambridge, Massachusetts 02138, USA
    J Cell Biol 144:139-49. 1999
    ..Collectively, these data show that the half-life of mature BMPs is greatly influenced by the identity of their pro regions...
  19. pmc Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice
    William C Wetsel
    Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, NC 27710
    Proc Natl Acad Sci U S A 110:17362-7. 2013
    ..and that mature BDNF protein levels are reduced in these brain areas in PC7 KO mice but not in the hippocampus of PC1/3 KO mice...
  20. pmc Nescient helix-loop-helix 2 interacts with signal transducer and activator of transcription 3 to regulate transcription of prohormone convertase 1/3
    Dana L Fox
    Department of Veterinary, University of Massachusets, Amherst, Massachusets 01002, USA
    Mol Endocrinol 22:1438-48. 2008
    ..Proopiomelanocortin is cleaved by prohormone convertase 1/3 (PC1/3) to produce peptides that regulate the body's response to energy availability...
  21. pmc The proprotein convertase PC1/3 regulates TLR9 trafficking and the associated signaling pathways
    M Duhamel
    Univ Lille, INSERM, U1192 Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse PRISM, F 59000 Lille, France
    Sci Rep 6:19360. 2016
    ..We have recently demonstrated that in macrophages, proprotein convertase 1/3 (PC1/3) is a key regulator of TLR4 Myd88-dependent signalling...
  22. doi Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions
    Mouna Saidi
    Groupe de recherche en pharmacologie animal du Québec GREPAQ, Département de Biomédecine Vétérinaire, Faculte de Medecine Veterinaire, Universite de Montreal, 3200 Sicotte, Saint Hyacinthe, QC, J2S 2M2, Canada
    Neurochem Res 40:2304-16. 2015
    ..The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e...
  23. doi Binding of MAGP2 to microfibrils is regulated by proprotein convertase cleavage
    Alison Miyamoto
    Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States Electronic address
    Matrix Biol 40:27-33. 2014
    ..Together, our data indicate that matrix localization of MAGP2 by its Matrix Binding Domain is promoted by PC cleavage and the presence of its C-terminal 20 amino acids. ..
  24. ncbi Biological processing of the cocaine and amphetamine-regulated transcript precursors by prohormone convertases, PC2 and PC1/3
    Arunangsu Dey
    Department of Biochemistry and Molecular Biology, The Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 278:15007-14. 2003
    ..pro-CART is a substrate for the neuroendocrine subtilisin/kexin-like prohormone convertases, PC2 (SPC2) and PC1/3 (SPC3)...
  25. ncbi Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide
    Lucy Marzban
    Department of Pathology and Laboratory Medicine and British Columbia Research Institute for Children s and Women s Health, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 53:141-8. 2004
    ..Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus...
  26. doi Preimplantation mouse embryo is a target for opioid ligand-receptor signaling
    Yongjie Chen
    State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People s Republic of China University of Chinese Academy of Sciences, Beijing, People s Republic of China
    Biol Reprod 91:4. 2014
    ....
  27. doi Cathepsin L participates in dynorphin production in brain cortex, illustrated by protease gene knockout and expression
    Ardalan Minokadeh
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
    Mol Cell Neurosci 43:98-107. 2010
    ..Comparative studies of PC1/3 and PC2 convertases showed that PC1/3 knockout mouse brains had a modest decrease in dynorphin A, and PC2 ..
  28. ncbi A switch from prohormone convertase (PC)-2 to PC1/3 expression in transplanted alpha-cells is accompanied by differential processing of proglucagon and improved glucose homeostasis in mice
    Rhonda D Wideman
    Department of Cellular and Physiological Sciences, Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Diabetes 56:2744-52. 2007
    ..In the enteroendocrine L-cell, proglucagon is differentially processed by the alternate enzyme PC1/3 to yield glucagon-like peptide (GLP)-1, GLP-2, and oxyntomodulin, which have blood glucose-lowering effects...
  29. pmc Necrostatin-1 attenuates mitochondrial dysfunction in neurons and astrocytes following neonatal hypoxia-ischemia
    R Chavez-Valdez
    Department of Pediatrics, Division of Neonatology, Johns Hopkins Medical Institutions, Johns Hopkins Hospital, 600 N Wolfe Street, CMSC 6 104, Baltimore, MD 21287, USA
    Neuroscience 219:192-203. 2012
    ..We conclude that Nec-1 immediately after HI, is strongly mitoprotective and prevents secondary energy failure by blocking early NO• accumulation, glutathione oxidation and attenuating mitochondrial dysfunction...
  30. doi Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine
    Jeffrey Gagnon
    The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9
    Regul Pept 152:54-60. 2009
    ..step towards elucidating these interactions, we have analyzed by immunohistochemistry the regional distribution of PCSK1, PCSK2 and PCSK3 in mouse SI as well as their cellular co-localization with substance P (SP), cholecystokinin (CCK)..
  31. ncbi Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor
    Randi Ugleholdt
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
    J Biol Chem 281:11050-7. 2006
    ..convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice. However, little is known about the endoproteolytic processing of the GIP precursor...
  32. pmc Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion
    Sarah Refaie
    Institut de Pharmacologie de Sherbrooke, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
    J Biol Chem 287:14703-17. 2012
    The proprotein convertase 1/3 is expressed in the regulated secretory pathway of neural and endocrine cells. Its major function is in the post-translational processing and activation of precursor proteins...
  33. pmc Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic α-cells in mouse models of ß-cell regeneration
    German Kilimnik
    Department of Medicine, The University of Chicago, Chicago, IL USA
    Islets 2:149-55. 2010
    ..Our study suggests an important role of α-cells for ß-cell proliferation and further for the endocrine cell network within an islet...
  34. pmc Analysis of peptides in prohormone convertase 1/3 null mouse brain using quantitative peptidomics
    Jonathan H Wardman
    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neurochem 114:215-25. 2010
    ..In this study, quantitative peptidomics analysis was used to characterize the specific role PC1/3 plays in this process...
  35. doi Alpha cell-specific Men1 ablation triggers the transdifferentiation of glucagon-expressing cells and insulinoma development
    JieLi Lu
    Laboratoire Génétique Moléculaire, Signalisation et Cancer, Centre National de Recherche Scientifique, UMR5201, Universite Claude Bernard Lyon1, Centre Leon Berard, Lyon, France
    Gastroenterology 138:1954-65. 2010
    ..The purpose of the current study was to address this issue in relation to islet tumor histogenesis...
  36. ncbi Murine subtilisin-like proteinase SPC6 is expressed during embryonic implantation, somitogenesis, and skeletal formation
    S L Rancourt
    Southern Alberta Cancer Research Centre, University of Calgary, Canada
    Dev Genet 21:75-81. 1997
    ..5: SPC1, SPC2, SPC3, and SPC6. In situ hybridization analysis of sectioned E6...
  37. ncbi Molecular cloning demonstrates structural features of homologous bovine prohormone convertases 1 and 2
    S R Hwang
    Department of Medicine, University of California, San Diego, La Jolla, USA
    DNA Cell Biol 19:409-19. 2000
    b>PC1 and PC2 (prohormone convertase) represent neuroendocrine members of the mammalian subtilisin-like family of proprotein convertases...
  38. ncbi Mouse chromosomal location of four Na/H exchanger isoform genes
    B G Pathak
    Mammalian Genetics Laboratory, NCI Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
    Genomics 31:261-3. 1996
    ..These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping...
  39. pmc NO donor induces Nec-1-inhibitable, but RIP1-independent, necrotic cell death in pancreatic β-cells
    Yoshiaki Tamura
    Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA
    FEBS Lett 585:3058-64. 2011
    ..Our findings raise the possibility that NO-mediated β-cell necrosis may be a novel form of signal-regulated necrosis, which play a role in the progression of diabetes...
  40. pmc Hysteretic behavior of proprotein convertase 1/3 (PC1/3)
    Marcelo Y Icimoto
    Departamento de Biofisica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
    PLoS ONE 6:e24545. 2011
    ..In this paper we demonstrate that mouse proprotein convertase 1/3 (mPC1/3) has a lag phase of activation by substrates that can be interpreted as a hysteretic behavior ..
  41. ncbi Altered processing of the neurotensin/neuromedin N precursor in PC2 knock down mice: a biochemical and immunohistochemical study
    Pierre Villeneuve
    Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    J Neurochem 82:783-93. 2002
    ..To gain insight into the role of prohormone convertases PC1, PC2, and PC7 in this process, we investigated the maturation of pro-NT/NN in the brain of PC7 (PC7-/-), PC2 (PC2-/-..
  42. pmc Cathepsin L participates in the production of neuropeptide Y in secretory vesicles, demonstrated by protease gene knockout and expression
    Lydiane Funkelstein
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0744, USA
    J Neurochem 106:384-91. 2008
    ..These studies illustrate the novel biological role of cathepsin L in the production of NPY, a peptide neurotransmitter, and neuroendocrine hormone...
  43. doi Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17
    Jens F Rehfeld
    Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
    Biochem J 415:35-43. 2008
    ..Antral G-cells synthesize the most gastrin and express PC1/3, 2 and 5/6 in the rat and human. But the cleavage sites in progastrin for each PC have not been determined...
  44. pmc A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing
    J F Martin
    Department of Biochemistry and Molecular Biology, University of Texas M D Anderson Cancer Center, Houston 77030
    Mol Cell Biol 14:1647-56. 1994
    ..The complexity of the MEF2 family of regulatory proteins provides the potential for fine-tuning of transcriptional responses as a consequence of combinatorial interactions among multiple MEF2 isoforms encoded by the four Mef2 genes...
  45. ncbi Cloning and structure of the human corticotrophin releasing factor-binding protein gene (CRHBP)
    D P Behan
    Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, San Diego, California 92037
    Genomics 16:63-8. 1993
    ..The promoter sequence contained a number of putative promoter elements including an AP-1 site, three ER-half sites, the immunoglobulin enhancer elements NF-kappa B and INF-1, and the liver-specific enhancers LFA1 and LFB1...
  46. ncbi Regional localization of three convertases, PC1 (Nec-1), PC2 (Nec-2), and furin (Fur), on mouse chromosomes
    N G Copeland
    Mammalian Genetics Laboratory, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Maryland 21702
    Genomics 13:1356-8. 1992
    The genes for three convertases, PC1 (Nec-1), PC2 (Nec-2), and furin (Fur), have been regionally localized on chromosomes 13, 2, and 7, respectively, by interspecific backcross analysis...
  47. pmc A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation
    Philip A Seymour
    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697 2300, USA
    Dev Biol 323:19-30. 2008
    ..Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD...
  48. doi Regulation and role of p21-activated kinase 3 by corticotropin-releasing factor in mouse pituitary
    Kazunori Kageyama
    Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036 8562, Japan
    Regul Pept 152:88-94. 2009
    ..Real-time PCR analysis revealed that p21-activated kinase 3 (Pak3), prohormone convertase type 1 (PC1), and CRF-binding protein (BP) mRNA expression levels were increased by CRF in AP cells...
  49. pmc Proteomic-based detection of a protein cluster dysregulated during cardiovascular development identifies biomarkers of congenital heart defects
    Anjali K Nath
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, United States of America
    PLoS ONE 4:e4221. 2009
    ..However, the molecular pathways that underlie these structural defects in humans remain largely unknown hindering the development of molecular-based diagnostic tools and novel therapies...
  50. ncbi Gene organization of the mouse pro-hormone and pro-protein convertase PC1
    N Ftouhi
    J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    DNA Cell Biol 13:395-407. 1994
    ..probe consisting of either the 5' end sequence or the full-length cDNA sequence of the mouse prohormone convertase PC1 (mPC1), we isolated from a lambda EMBL3 mouse genomic library two clones that coded for the 5' and 3' ends of the ..
  51. doi Targeted production of proprotein convertase PC1 enhances mammary development and tumorigenesis in transgenic mice
    Anne Blanchard
    Department of Physiology, University of Manitoba, Winnipeg, MB R3E 0W3, Canada
    Can J Physiol Pharmacol 87:831-8. 2009
    ..Mammary epithelium-specific and early expression of PC1 was targeted by the use of the mouse mammary tumor virus promoter/enhancer...
  52. ncbi Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets
    M Marcinkiewicz
    J A DeSève Laboratories of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    Endocrinology 135:1651-60. 1994
    The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets...
  53. ncbi The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions
    N G Seidah
    JA DeSève Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Que, Canada
    Biochimie 76:197-209. 1994
    ..These subtilisin/kexin-like convertases were called furin/PACE, PC1/PC3, PC2, PACE4, PC4 and PC5/PC6...
  54. pmc The transcription factor Rfx3 regulates beta-cell differentiation, function, and glucokinase expression
    Aouatef Ait-Lounis
    Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Centre Medical Universitaire, Geneva, Switzerland
    Diabetes 59:1674-85. 2010
    ..The objective of this work was to unravel the cellular and molecular mechanisms underlying this deficiency...
  55. pmc Modulation of prohormone convertase 1/3 properties using site-directed mutagenesis
    Akihiko Ozawa
    Department of Anatomy and Neurobiology, University of Maryland, Baltimore, 20 Penn Street, Health Sciences Facility II Room S251, Baltimore, Maryland 21201, USA
    Endocrinology 151:4437-45. 2010
    ..Compared with PC2, recombinant PC1/3 exhibits a very low specific activity against both small fluorogenic peptides and recombinant precursors, even ..
  56. ncbi Processing of mouse proglucagon by recombinant prohormone convertase 1 and immunopurified prohormone convertase 2 in vitro
    M E Rothenberg
    Department of Anatomy and Cell Biology, Emory University, Atlanta, Georgia 30322, USA
    J Biol Chem 270:10136-46. 1995
    ..b>PC1 was also immunolocalized in secretory granules...
  57. pmc Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst
    Daniel Mesnard
    Swiss Federal Institute of Technology Lausanne, School of Life Sciences, Swiss Institute for Experimental Cancer Research, CH 1015 Lausanne, Switzerland
    J Cell Biol 191:129-39. 2010
    ..The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo...
  58. pmc Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage
    Simon Kordowich
    Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg, Gottingen, Germany
    BMC Dev Biol 11:52. 2011
    ..2-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of Nkx2.2/Arx single- and double-mutants but also of Pax6-deficient animals...
  59. ncbi cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases
    N G Seidah
    J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    DNA Cell Biol 9:415-24. 1990
    ..8 kb) demonstrated tissue and cellular specificity of expression, only within endocrine and neuroendocrine cells. These data suggest that mPC1 and mPC2 represent prime candidates for tissue-specific pro-hormone converting proteinases...
  60. ncbi Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, Furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2
    N G Seidah
    J A DeSève Laboratories of Biochemical, Clinical Research Institute of Montreal, Quebec, Canada
    Mol Endocrinol 5:111-22. 1991
    ..tripeptide identical to the recognition sequence of integrins was observed in the structures of the mammalian PC1, PC2, and Furin...
  61. pmc Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans
    S P Smeekens
    Howard Hughes Medical Institute, University of Chicago, IL 60637
    Proc Natl Acad Sci U S A 88:340-4. 1991
    ..We have used the polymerase chain reaction to identify and clone a cDNA (PC3) from the mouse AtT20 anterior pituitary cell line that represents an additional member of this growing family of ..
  62. ncbi Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region)
    N G Seidah
    J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    Genomics 11:103-7. 1991
    ..Furthermore, the identification of the NEC1 locus on human chromosome 5 and mouse chromosome 13 suggests a conservation of synthenic regions between these ..
  63. ncbi Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus
    Michael A Tangrea
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA
    J Mol Biol 320:801-12. 2002
    ..eukaryotic PC pro-domains will have the same overall fold and most of the residues forming the hydrophobic core of PC1 are highly conserved within the PC family...
  64. pmc Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex
    Toshihiko Masui
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Genes Dev 21:2629-43. 2007
    ..Action within an organ-specific transcription factor is a previously unknown function for RBPJ and is independent of its role in Notch signaling...
  65. ncbi Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis
    M Vincent
    Department of Anatomy and Cell Biology, State University of New York, Brooklyn, New York 11203, USA
    Endocrinology 144:4061-9. 2003
    ..These results indicate that hormones processed by PC2 affected processes that regulate islet cell differentiation and maturation in embryos and adults...
  66. ncbi The prohormone processing enzyme PC3 is a lipid raft-associated transmembrane protein
    Irina Arnaoutova
    Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 4480, USA
    Biochemistry 42:10445-55. 2003
    The biosynthesis of most biologically active peptides involves the action of prohomone convertases, including PC3 (also known as PC1), that catalyze limited proteolysis of precursor proteins...
  67. ncbi The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease
    R Winsky-Sommerer
    INSERM U549, IFR Broca Sainte Anne, Centre Paul Broca, 2 ter rue d Alesia, 75014 Paris, France
    Neuroscience 122:437-47. 2003
    ..By immunohistochemistry, PC1 and PC2 were localized in many neuronal elements in human frontal and temporal cortex...
  68. ncbi Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1
    Randi Ugleholdt
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, DK 2200 Copenhagen N, Denmark
    Endocrinology 145:1349-55. 2004
    The neuroendocrine prohormone convertases 1 and 2 (PC1 and PC2) are expressed in endocrine intestinal L cells and pancreatic A cells, respectively, and colocalize with proglucagon in secretory granules...
  69. ncbi Identification of two chromosomal loci determining glucose intolerance in a C57BL/6 mouse strain
    T Kayo
    Department of Hygiene, Akita University School of Medicine, Japan
    Comp Med 50:296-302. 2000
    ..05) at 10, 20, and 30 minutes during the intraperitoneal glucose tolerance test (IPGTT: 1.5 g glucose/kg of body weight)...
  70. ncbi ProSAAS and prohormone convertase 1 are broadly expressed during mouse development
    Yun Feng
    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Brain Res Gene Expr Patterns 1:135-40. 2002
    ..ProSAAS and its processing intermediates are also potent inhibitors of prohormone convertase 1 (PC1), which is encoded by mouse gene Pcsk1...
  71. ncbi Genetic inactivation of prohormone convertase (PC1) causes a reduction in cholecystokinin (CCK) levels in the hippocampus, amygdala, pons and medulla in mouse brain that correlates with the degree of colocalization of PC1 and CCK mRNA in these structures
    B M Cain
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Neurochem 89:307-13. 2004
    ..b>Prohormone convertase 1 (PC1) has a distribution that is similar to cholecystokinin (CCK) in rat brain...
  72. ncbi On the tissue-specific processing of procholecystokinin in the brain and gut--a short review
    J F Rehfeld
    University Department of Clinical Biochemistry Rigshospitalet, Copenhagen, Denmark
    J Physiol Pharmacol 54:73-9. 2003
    ..Of these, PC1 and PC2 are expressed in cerebral neurons and intestinal endocrine cells...
  73. ncbi Knock-in of diphteria toxin A chain gene at Ins2 locus: effects on islet development and localization of Ins2 expression in the brain
    Luciane Lamotte
    Institut Cochin, INSERM U567, CNRS UMR 8104, Universite Rene Descartes, Departement Genetique, Developpement et Pathologie Moleculaire, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    Transgenic Res 13:463-73. 2004
    ..Transcripts for other key beta-cell markers, with the notable exception of Pdx-1, were also found in CP RNAs. These results must revive interest in studies focused on extrapancreatic insulin gene expression...
  74. ncbi Neuropeptide processing profile in mice lacking prohormone convertase-1
    Hui Pan
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York 10029, USA
    Biochemistry 44:4939-48. 2005
    b>Prohormone convertase 1 (PC1; also known as PC3) is believed to be responsible for the processing of many neuropeptide precursors...
  75. pmc Endocrinomic profile of neurointermediate lobe pituitary prohormone processing in PC1/3- and PC2-Null mice using SELDI-TOF mass spectrometry
    Atira Hardiman
    Department of Pharmacology and Toxicology, School of Medicine, Wright State University, Dayton, Ohio 45435, USA
    J Mol Endocrinol 34:739-51. 2005
    ..Neurointermediate lobe pituitaries from normal (+/+), heterozygous (+/-), PC2-Null (-/-), PC1/3-Null and oxytocin-Null mice were analyzed by SELDI-TOF mass spectroscopy for the peptide hormone products, AVP, ..
  76. ncbi Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines
    E Decroly
    Laboratoire de Chimie Physique des Macromolecules aux Interfaces, CP206 2, Universite Libre de Bruxelles, 1050, Brussels, Belgium
    J Biol Chem 271:30442-50. 1996
    ..The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the major gp160-converting enzymes in T4 lymphocytes...
  77. pmc Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation
    Patricia M Vuguin
    Division of Pediatric Endocrinology, Children s Hospital at Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10476, USA
    Endocrinology 147:3995-4006. 2006
    ..These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature alpha-cell phenotype...
  78. ncbi Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice
    David J Lloyd
    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, La Jolla, CA 92121, USA
    Hum Mol Genet 15:1884-93. 2006
    b>Prohormone convertase 1 (PC1) mutations lead to obesity in humans...
  79. ncbi On the processing of proghrelin to ghrelin
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology and Howard Hughes Medical Institute, The University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
    J Biol Chem 281:38867-70. 2006
    ..mass spectrometry, and immunocytochemical methods, we have demonstrated that (a) in mouse stomach, prohormone convertase 1/3 (PC1/3) is the endoprotease responsible for the conversion of proghrelin to ghrelin, (b) the acylation ..
  80. ncbi A targeted deletion/insertion in the mouse Pcsk1 locus is associated with homozygous embryo preimplantation lethality, mutant allele preferential transmission and heterozygous female susceptibility to dietary fat
    Majambu Mbikay
    Ottawa Health Research Institute and The Ottawa Hospital, 725 Parkdale Avenue, Ottawa, Ontario, Canada
    Dev Biol 306:584-98. 2007
    b>Proprotein convertase 1 (PC1) is a neuroendocrine proteinase involved in the proteolytic activation of precursors to hormones and neuropeptides...
  81. ncbi The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells
    Shelley B Nelson
    Department of Developmental and Cell Biology, University of California at Irvine, 4203 McGaugh Hall, Irvine, CA 92697 2300, USA
    Development 134:2491-500. 2007
    ..2 in endocrine differentiation are a consequence of their divergent spatiotemporal expression domains rather than their biochemical activities and implies that both Nkx6.1 and Nkx6.2 possess alpha- and beta-cell-specifying activities...
  82. ncbi The C-terminal region of the proprotein convertase 1/3 (PC1/3) exerts a bimodal regulation of the enzyme activity in vitro
    Nadia Rabah
    Neuropeptides Structure and Metabolism Laboratory, Institut de Recherches Cliniques de Montreal, Quebec, Canada
    FEBS J 274:3482-91. 2007
    The proprotein convertase PC1/3 preferentially cleaves its substrates in the dense core secretory granules of endocrine and neuroendocrine cells...
  83. pmc Ontogeny of the prohormone convertases PC1 and PC2 in the mouse hypophysis and their colocalization with corticotropin and alpha-melanotropin
    M Marcinkiewicz
    J A DeSève Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    Proc Natl Acad Sci U S A 90:4922-6. 1993
    ..POMC products are likely the result of differential expression of the two known prohormone convertases PC1 and PC2...
  84. pmc The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6
    Jens F Rehfeld
    Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
    Endocrinology 149:1600-8. 2008
    ..In PC1/3 null mice, the synthesis of bioactive CCK peptide in the gut was reduced to 3% of the translational product, all ..
  85. ncbi Kainic acid increases the expression of the prohormone convertases furin and PC1 in the mouse hippocampus
    A Meyer
    J A DeSève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
    Brain Res 732:121-32. 1996
    ..To study the interrelationships between the convertases furin, PC1 and PC2, and the neurotrophins NGF, BDNF and NT-3, we compared their mRNA distribution in different tissues...
  86. pmc Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease
    Jimmy D Dikeakos
    Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Montreal, QC, Canada H2W 1R7
    Proc Natl Acad Sci U S A 106:7408-13. 2009
    ..Prohormone convertase (PC)1/3 is a processing protease that is targeted to DCSGs. The signal for targeting PC1/3 to DCSGs resides in its carboxy-terminal tail (PC1/3(617-753)), where 3 regions (PC1/3(617-625), PC1/3(665-682), ..
  87. ncbi Furin and prohormone convertase 1/3 are major convertases in the processing of mouse pro-growth hormone-releasing hormone
    Arunangsu Dey
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA
    Endocrinology 145:1961-71. 2004
    We investigated the proteolytic processing of mouse pro-GHRH [84 amino acids (aa)] by furin, PC1/3, PC2, and PC5/6A...
  88. ncbi cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases
    N G Seidah
    DNA Cell Biol 9:789. 1990
  89. pmc Isolation and functional expression of a mammalian prohormone processing enzyme, murine prohormone convertase 1
    J Korner
    Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032
    Proc Natl Acad Sci U S A 88:6834-8. 1991
    ..The coinjection of RNA encoding murine prohormone convertase 1 (mPC1), a mammalian endoprotease, along with proopiomelanocortin RNA into an oocyte results in the ..
  90. ncbi Cloning and functional expression of a novel endoprotease involved in prohormone processing at dibasic sites
    K Nakayama
    Institute of Biological Sciences, University of Tsukuba, Ibaraki
    J Biochem 109:803-6. 1991
    ..This cDNA encodes a novel 753-residue protein, named PC3, which is structurally related to the yeast Kex2 protease involved in precursor cleavage at dibasic sites and to ..
  91. ncbi The Arg617-Arg618 cleavage site in the C-terminal domain of PC1 plays a major role in the processing and targeting of the enzyme within the regulated secretory pathway
    Natacha Bernard
    Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR 6097, Valbonne, France
    J Neurochem 85:1592-603. 2003
    The C-terminal domain of the prohormone convertase PC1 is involved in targeting of the enzyme to secretory granules in neuroendocrine cells and is subsequently processed in this compartment at an Arg617-Arg618 site...

Research Grants2

  1. 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. ..
  2. Nutrition, Early Development and Glucose Metabolism
    Patricia Vuguin; Fiscal Year: 2007
    ..abstract_text> ..