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| proprotein convertasesSummarySummary: Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES. Top Publications
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Publications
Regulation of Pcsk6 expression during the preantral to antral follicle transition in mice: opposing roles of FSH and oocytesFrancisco J Diaz
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Biol Reprod 78:176-83. 2008..The proprotein convertases are a family of seven known proteins that process TGFbeta ligands and other secreted products to their ..- Inhibition of proprotein convertases: approaches to block squamous carcinoma development and progressionRicardo López de Cicco
Department of Pathology and Tumor Cell Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Mol Carcinog 46:654-9. 2007..PDX and CMK have also been assayed in vivo using skin carcinogenesis models. Newer promising small molecules and RNA interference approaches are also being developed to inhibit PCs... 
What lies ahead for the proprotein convertases?Nabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Canada
Ann N Y Acad Sci 1220:149-61. 2011..In vivo studies demonstrated that PCs play major roles in health and disease states...
SPC4/PACE4 regulates a TGFbeta signaling network during axis formationD B Constam
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138 USA
Genes Dev 14:1146-55. 2000..These findings establish an important role for SPC4 in patterning the early mouse embryo...- Cell-surface processing of extracellular human immunodeficiency virus type 1 Vpr by proprotein convertasesYong Xiao
Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montreal, Montreal, Quebec, Canada
Virology 372:384-97. 2008..Collectively, these results suggest that cell surface processing of extracellular Vpr by PCs might regulate the levels of active soluble Vpr... - Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory responseKezhong Zhang
Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Cell 124:587-99. 2006..Together, our studies delineate a molecular mechanism for activation of an ER-localized transcription factor, CREBH, and reveal an unprecedented link by which ER stress initiates an acute inflammatory response... - Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertasesGeraldine Siegfried
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7
Oncogene 24:6925-35. 2005..Our findings emphasize the importance of the convertase-directed processing of proPDGF-B at the RGRR81/ sequence for PDGF-B maturation and secretion... - Shedding of collagen XXIII is mediated by furin and depends on the plasma membrane microenvironmentGuido Veit
Center for Biochemistry, Medical Faculty, University of Cologne, Joseph Stelzmannstrasse 52, 50931 Cologne, Germany
J Biol Chem 282:27424-35. 2007..These mechanisms allow the cell to regulate the amounts of cell surface-bound and secreted collagen XXIII... - Proprotein convertases: lessons from knockoutsNathalie Scamuffa
INSERM U716/ Equipe AVENIR, , 27 rue Juliette Dodu, 75010 Paris, France
FASEB J 20:1954-63. 2006The physiological role of the subtilisin/kexin-like proprotein convertases (PCs) in rodents has been examined through the use of knockout mice... - Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopyI Takumi
Department of Neurosurgery, Nippon Medical School, Sendagi, Tokyo, Japan
Mod Pathol 11:232-8. 1998..The high incidence of PC1/3 and PC2 in nonfunctioning adenomas might be related to the processing of chromogranin A... - Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4T Nakagawa
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki
J Biochem 113:132-5. 1993..Transfection experiments revealed that PC6 was capable of cleaving precursors at dibasic sites. These observations suggest that PC6 is a candidate for a processing endoprotease responsible for the maturation of gastrointestinal peptides... - Histidine-rich human salivary peptides are inhibitors of proprotein convertases furin and PC7 but act as substrates for PC1A Basak
Laboratory of Structure and Metabolism of Neuropeptides, Clinical Research Institute of Montreal, Quebec, Canada
J Pept Res 49:596-603. 1997..The behavior of these five peptides was examined with three proprotein convertases (PC's) which possess cleavage specificity directed towards single and pairs of basic residues... - Bioactivation of Müllerian inhibiting substance during gonadal development by a kex2/subtilisin-like endoproteaseM W Nachtigal
Department of Physiology, Program in Developmental Biology, University of California, San Francisco 94143 0444, USA
Proc Natl Acad Sci U S A 93:7711-6. 1996..Our results suggest that MIS is a natural substrate for PC5, thereby supporting a role for prohormone convertases in the activation of transforming growth factor beta-related hormones during development... - Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localizationN G Seidah
Laboratory of Biochemical, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada H2W 1R7
Proc Natl Acad Sci U S A 96:1321-6. 1999..In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of pro-brain-derived neurotrophic factor... - Proprotein convertases are important mediators of the adipocyte differentiation of mouse 3T3-L1 cellsGilles Croissandeau
Diseases of Aging Program, Ottawa Health Research Institute at Ottawa Hospital, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4K9, Canada
J Cell Sci 115:1203-11. 2002..In this study, we show that expression of the proprotein convertases PACE4, PC7 and furin increases when 3T3-L1 cells are induced to differentiate into adipocytes... - Hepatic proprotein convertases modulate HDL metabolismWeijun Jin
Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Cell Metab 6:129-36. 2007..Here we show that inhibition in the liver of the classical proprotein convertases (PCs), but not the atypical PCs S1P and PCSK9, decreases plasma HDL-C levels... - Tissue distribution and processing of proSAAS by proprotein convertasesM Sayah
Department of Biochemistry and Molecular Biology, LSU Health Science Center, New Orleans, LA 70112, USA
J Neurochem 76:1833-41. 2001..Whereas the C-terminal peptide is mostly internally cleaved in wild-type mouse brain, it is not processed as efficiently in the brain of PC2 null mice, suggesting that PC2 is partially responsible for this cleavage in vivo... - Comparative study of the binding pockets of mammalian proprotein convertases and its implications for the design of specific small molecule inhibitorsSun Tian
Institute of Biomechanics School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China
Int J Biol Sci 6:89-95. 2010b>Proprotein convertases are enzymes that proteolytically cleave protein precursors in the secretory pathway to yield functional proteins... - Precursor processing by kex2/furin proteasesNathan C Rockwell
Department of Biological Chemistry, University of Michigan Medical Center, Room 5413 Med Sci I, 1301 East Catherine, Ann Arbor Michigan 48109, USA
Chem Rev 102:4525-48. 2002 - Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defectsXiaorong 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. 2002The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway... - Site-1 protease is required for cartilage development in zebrafishKornelia Schlombs
Exelixis Deutschland, Spemannstrasse 35, 72076 Tuebingen, Germany
Proc Natl Acad Sci U S A 100:14024-9. 2003..This indicates that the cartilage phenoptypes of goz are caused independently of the lipid defects... - Development of protein-based inhibitors of the proprotein of convertase SKI-1/S1P: processing of SREBP-2, ATF6, and a viral glycoproteinPhilomena Pullikotil
Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 279:17338-47. 2004..Finally, these inhibitors were also shown to affect the processing and stability of the Crimean-Congo hemorrhagic fever virus glycoprotein... - Elevated expression of proprotein convertases alters breast cancer cell growth in response to estrogen and tamoxifenM Cheng
Department of Physiology, Faculty of Medicine, University of Manitoba, 770 Bannatyne, Winnipeg, Manitoba, Canada R3E 0W3
J Mol Endocrinol 26:95-105. 2001..This study shows that the over-expression of proprotein convertases confers a greater estrogen dependency and anti-estrogen resistance on human breast cancer cells. - Structural basis for differences in substrate selectivity in Kex2 and furin protein convertasesTodd Holyoak
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA
Biochemistry 43:2412-21. 2004..In addition, several monovalent cation binding sites are identified, and a mechanism of activation of Kex2 by potassium ion is proposed... - Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumoursM Mbikay
Institut de Recherches Cliniques de Montreal, Universite de Montreal, Quebec, Canada
Br J Cancer 75:1509-14. 1997b>Proprotein convertases mediate the production of a variety of peptidic mitogens by limited proteolysis of their precursors... - The KEX2 gene of Candida glabrata is required for cell surface integrityO Bader
, Angewandte Molekularbiologie III, , Ohnhorststr. 18, 22609 Hamburg, Germany
Mol Microbiol 41:1431-44. 2001..These data suggest that Kex2 is involved in the processing of proteins that are essential for cell surface integrity of C. glabrata... - Lipopolysaccharide mediated regulation of neuroendocrine associated proprotein convertases and neuropeptide precursor processing in the rat spleenGuillaume Lansac
Departement de Pharmacologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4
J Neuroimmunol 171:57-71. 2006Within the secretory pathway, the family of proprotein convertases cleave inactive precursors at paired basic residues to generate a myriad of biologically active peptides... - Curbing activation: proprotein convertases in homeostasis and pathologyNeil A Taylor
Laboratory of Molecular Oncology, Department for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Gasthuisberg O/N 6, Herestraat 49, B-3000 Leuven, Belgium
FASEB J 17:1215-27. 2003The proprotein convertases (PCs) are a seven-member family of endoproteases that activate proproteins by cleavage at basic motifs. Expression patterns for individual PCs vary widely, and all cells express several members... - Purification and characterization of the yeast glycosylphosphatidylinositol-anchored, monobasic-specific aspartyl protease yapsin 2 (Mkc7p)H Komano
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
J Biol Chem 274:24431-7. 1999..0. However, V(max)/K(m) for a substrate mimicking the alpha-secretase site in human beta amyloid precursor protein was optimal near pH 6.0, consistent with cleavage of beta amyloid precursor protein by yapsin 2 when expressed in yeast... - Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1PWinfried R Beyer
Heinrich Pette Institut fur experimentelle Virologie und Immunologie an der Universitat Hamburg, D 20251 Hamburg, Germany
J Virol 77:2866-72. 2003..In agreement with the identified consensus motif, we show that the cellular subtilase SKI-1/S1P cleaves LCMV GP... - Extraembryonic proteases regulate Nodal signalling during gastrulationSéverine Beck
Developmental Biology Group, Swiss Institute for Experimental Cancer Research ISREC, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
Nat Cell Biol 4:981-5. 2002..Here we show that the proprotein convertases Spc1 and Spc4 (also known as Furin and Pace4, respectively) are expressed in adjacent extraembryonic .. - Inactivation of Kex2p diminishes the virulence of Candida albicansGeorge Newport
Department of Stomatology, University of California at San Francisco, California 94143-0422, USA
J Biol Chem 278:1713-20. 2003..Kexins also process fungal mating pheromones; a modification of the algorithm identified a putative mating pheromone with structural similarities to Saccharomyces cerevisiae alpha-factor... - Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cellsJ Sakai
Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas 75235, USA
Mol Cell 2:505-14. 1998..The cDNA encodes S1P, an intraluminal 1052-amino-acid membrane-bound subtilisin-like protease. We propose that S1P is the sterol-regulated protease that controls lipid metabolism in animal cells... - The proteolytic processing of pro-platelet-derived growth factor-A at RRKR(86) by members of the proprotein convertase family is functionally correlated to platelet-derived growth factor-A-induced functions and tumorigenicityGeraldine Siegfried
Laboratory of Biochemical Neuroendocrinology Clinical Research Institute of Montreal, Montreal, Quebec, H2W 1R7, Canada
Cancer Res 63:1458-63. 2003..Pro-PDGF-A processing occurs at pairs of basic residues, likely involving the proprotein convertases (PCs). In the colon carcinoma cell line LoVo, we found that Furin is the most potent PDGF-A convertase... - Effect of amino acid substitution at the P(3) and P(4) subsites of fusion proteins on kex2 protease activityY Suzuki
Suntory Institute for Medicinal Research and Development, 2716 1 Akaiwa, Chiyoda Machi, Ohra Gun, Gunma 370 0503, Japan
Biotechnol Appl Biochem 32:53-60. 2000..5 once purified in urea-free solution. Thus Kex2 exhibited extended substrate specificity beyond P(2)-P(1) in the cleavage of the fusion proteins, although it depended on the reaction conditions... - 2.4 A resolution crystal structure of the prototypical hormone-processing protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitorTodd Holyoak
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA
Biochemistry 42:6709-18. 2003..The P-domain of ssKex2 has a novel jelly roll like fold consisting of nine beta strands and may potentially be involved, along with the buried Ca(2+) ion, in creating the highly determined binding site for P(1) arginine... - Regulation of bone morphogenetic protein activity by pro domains and proprotein convertasesD 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... - Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirusEric Bergeron
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Que, Canada H2W 1R7
Biochem Biophys Res Commun 326:554-63. 2005..The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the approximately 80 kDa protein... - XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus developmentBilge Birsoy
Division of Developmental Biology, Cincinnati Children s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Development 132:591-602. 2005..We conclude that maternal XPACE4 plays an important role in embryonic patterning by regulating the production of a subset of active mature TGFbeta proteins in specific sites... - Proprotein convertases modulate budding and branching morphogenesis of rat ventral prostateKatsunori Uchida
Nephro Urologic Surgery and Andrology, Division of Reparative and Regenerative Medicine, Mie University Graduate School of Medicine, Mie, Japan
Int J Dev Biol 51:229-33. 2007The onset of prostate morphogenesis is involved in the interaction between mesenchyme and epithelium. Proprotein convertases (PCs) activate a variety of growth and differentiation factors including mesenchymal and epithelial factors, such .. - Regulation of prohormone convertases in hypothalamic neurons: implications for prothyrotropin-releasing hormone and proopiomelanocortinEduardo A Nillni
Division of Endocrinology, Department of Medicine, Brown Medical School Rhode Island Hospital, 55 Claverick Street, Third Floor, Room 320, Providence, Rhode Island 02903, USA
Endocrinology 148:4191-200. 2007..Therefore, the coupled regulation of proneuropeptide/processing enzymes may be a common process, by which cells generate more effective processing of prohormones into mature peptides... - Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membraneS F Nothwehr
Institute of Molecular Biology, University of Oregon, Eugene 97403
J Cell Biol 129:35-46. 1995..We propose a model in which Vps1p is required for formation of vesicles from the late Golgi apparatus that carry vacuolar and Golgi membrane proteins bound for the prevacuolar compartment... - Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancerRobert E Page
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Cell Oncol 29:289-99. 2007b>Proprotein convertases (PCs) are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and .. - Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine proteaseR S Fuller
Department of Biochemistry, University of California, Berkeley 94720
Proc Natl Acad Sci U S A 86:1434-8. 1989..Mutant enzyme molecules lacking as many as 200 C-terminal residues still retained Ca2+-dependent protease activity and were labeled by 125I-labeled Tyr-Ala-Lys-Arg-chloromethyl ketone... - Proprotein convertases as therapeutic targetsMichel Chretien
University of Ottawa, The Ottawa Hospital, Ottawa Health Research Institute, Chronic Disease Program, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada
Expert Opin Ther Targets 12:1289-300. 2008..is principally mediated by a family of calcium-dependent serine proteases, generically known as proprotein convertases. Altered expression of these enzymes in experimental animal models and in humans has been associated with .. - Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells' malignant phenotypes: role of tissue inhibitors of metalloproteinase-1Marion Lapierre
INSERM U716, Team AVENIR, Institut de Genetique Moleculaire, Universite Paris 7, Paris, France
Cancer Res 67:9030-4. 2007Proteolytic cleavage of various cancer-related substrates by the proprotein convertases (PC) was reported to be important in the processes of neoplasia... - The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substratesGaetan Mayer
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 283:2373-84. 2008The proprotein convertases are synthesized as zymogens that acquire activity upon autocatalytic removal of their NH(2)-terminal prosegment... - Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cellsNathalie Scamuffa
INSERM U716, Equipe Avenir, Institut de Genetique Moleculaire, and Université Paris 7, Paris, France
J Clin Invest 118:352-63. 2008The proprotein convertases (PCs) are implicated in the activation of various precursor proteins that play an important role in tumor cell metastasis... - VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5Dorota Szumska
Department of Cardiovascular Medicine and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom
Genes Dev 22:1465-77. 2008..We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development... - Proteases for processing proneuropeptides into peptide neurotransmitters and hormonesVivian Hook
Skaggs School of Pharmacy and Pharmaceutical Sciences, and Department of Neuroscience, Pharmacology, and Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093 0744, USA
Annu Rev Pharmacol Toxicol 48:393-423. 2008..Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease... - Inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small moleculesTomoko Komiyama
Departments of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
J Biol Chem 284:15729-38. 2009.... - The proprotein convertases are potential targets in the treatment of dyslipidemiaNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, H2W 1R7, Canada
J Mol Med (Berl) 85:685-96. 2007The family of the secretory proprotein convertases (PCs) comprises seven basic amino acid (aa)-specific subtilisin-like serine proteinases known as PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7, and two other PCs, SKI-1 (subtilisin-kexin .. - Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertasesYannick Bontemps
INSERM, U 716, Equipe Avenir, Institut de Genetique Moleculaire, Paris 75010, France
Med Res Rev 27:631-48. 2007The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g... - Reduced proteolysis of secreted gelatin and Yps1-mediated alpha-factor leader processing in a Pichia pastoris kex2 disruptantMarc W T Werten
Agrotechnology and Food Innovations B V, Wageningen UR, Bornsesteeg 59, NL 6708 PD Wageningen, The Netherlands
Appl Environ Microbiol 71:2310-7. 2005..pastoris kex2 and yps1 single-gene disruptants can be used for the alpha-factor leader-directed secretion of heterologous proteins otherwise degraded at basic residues... - Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibitionMartin Fugere
Institut de Pharmacologie de Sherbrooke, Departement de Pharmacologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
Trends Pharmacol Sci 26:294-301. 2005..Based on this information, we review the latest strategies to inhibit PCs, which might lead to the development of specific compounds... - Proprotein convertases [corrected] are responsible for proteolysis and inactivation of endothelial lipaseWeijun Jin
Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennyslvania 19104, USA
J Biol Chem 280:36551-9. 2005..This action is unusual for PCs, which are traditionally known as activators of pro-proteins, and highlights a potential role of PCs in lipid metabolism through their proteolytic processing of lipases... - Endo/exo-proteolysis in neoplastic progression and metastasisAbdel-Majid Khatib
J Mol Med 83:856-64. 2005..In recent years, growing evidence has accumulated for the important role of proprotein convertases (PCs) and peptide alpha-amidation enzymes in these processes... - The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinasesNadia Nour
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
Mol Biol Cell 16:5215-26. 2005The proprotein convertases PC5, PACE4 and furin contain a C-terminal cysteine-rich domain (CRD) of unknown function... - The proprotein convertase SKI-1/S1P. In vitro analysis of Lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitorsAntonella Pasquato
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
J Biol Chem 281:23471-81. 2006.... - The proprotein convertases and their implication in sterol and/or lipid metabolismNabil G Seidah
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal H2W 1R7, QC, Canada
Biol Chem 387:871-7. 2006The proprotein convertases represent a family of nine proteinases, comprising seven basic amino acid-specific subtilisin-like serine proteinases related to yeast kexin, known as PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7, and two other .. - The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4Nadav Ben-Haim
Ecole Polytechnique Fédérale de Lausanne EPFL ISREC, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
Dev Cell 11:313-23. 2006During early mouse development, the subtilisin-like proprotein convertases (SPC) Furin and PACE4 pattern the primitive ectoderm and visceral endoderm, presumably by activating the TGFss-related Nodal precursor... - Site 1 protease is required for proteolytic processing of the glycoproteins of the South American hemorrhagic fever viruses Junin, Machupo, and GuanaritoJillian M Rojek
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA
J Virol 82:6045-51. 2008..Infection of S1P-deficient cells resulted in viral persistence over several weeks without the emergence of escape variants able to use other cellular proteases for GP processing... - Isolation and characterization of VGF peptides in rat brain. Role of PC1/3 and PC2 in the maturation of VGF precursorE Trani
Istituto di Neurobiologia e Medicina Molecolare, CNR, Roma, Italy
J Neurochem 81:565-74. 2002.... - CCK processing by pituitary GH3 cells, human teratocarcinoma cells NT2 and hNT differentiated human neuronal cells evidence for a differentiation-induced change in enzyme expression and pro CCK processingMargery C Beinfeld
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
Life Sci 70:1251-8. 2002..These results also support the hypothesis that PC5 in differentiated neuronal cells is capable of processing pro CCK to glycine-extended CCK 8... - A critical role for the carboxy terminal region of the proprotein convertase, PACE4A, in the regulation of its autocatalytic activation coupled with secretionTakazumi Taniguchi
Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minamijosanjima, Tokushima, 770-8506, Japan
Biochem Biophys Res Commun 290:878-84. 2002..These findings indicate that PACE4A activity is highly controlled by a unique system at post-translational level... - Biosynthetic processing of the pro-alpha 1(V)2pro-alpha 2(V) collagen heterotrimer by bone morphogenetic protein-1 and furin-like proprotein convertasesChristine Unsöld
Department of Pathology, University of Wisconsin, Madison, Wisconsin 53706, USA
J Biol Chem 277:5596-602. 2002..pro-alpha1(V)(2)pro-alpha2(V) heterotrimers, pro-alpha1(V) N-propeptides and pro-alpha2(V) C-propeptides are processed by BMP-1-like enzymes, and pro-alpha1(V) C-propeptides are processed by furin-like proprotein convertases in vivo. - Proteolytic processing of the hepatitis B virus e antigen precursor. Cleavage at two furin consensus sequencesFabienne Messageot
, Gif sur Yvette, 91198 France
J Biol Chem 278:891-5. 2003..In addition, we show that in our experimental system, the HBeAg is a 164-amino acid protein and not a 159-amino acid protein as previously reported... - The disulphide mapping, folding and characterisation of recombinant Ber e 1, an allergenic protein, and SFA8, two sulphur-rich 2S plant albuminsMarcos J C Alcocer
School of Life and Environmental Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
J Mol Biol 324:165-75. 2002..The secreted production of these properly folded sulphur-rich plant albumins presents an opportunity to delineate the attributes that make an allergen and to facilitate the diagnosis and therapy of type I allergy... - Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometriumC Freyer
Prince Henry s Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia
Reproduction 133:1189-97. 2007.... - The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM)E Decroly
Laboratoire de Chimie Physique des Macromolecules aux Interfaces, Universite Libre de Bruxelles, Belgium
J Biol Chem 269:12240-7. 1994..Transition state analog peptides were designed and tested in vitro for their ability to inhibit the PC1- or furin-mediated gp160 cleavage. The best inhibitor was decanoyl-Arg-Lys-Arg-Arg-psi [CH2NH]-Phe-Leu-Gly-Phe-NH2... - Barley serine proteinase inhibitor 2-derived cyclic peptides as potent and selective inhibitors of convertases PC1/3 and furinMichele Villemure
Neuropeptides Structure and Metabolism Unit, Institut de Recherches Cliniques de Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
Biochemistry 42:9659-68. 2003b>Proprotein convertases (PCs) are serine proteases containing a subtilisin-like catalytic domain that are involved in the conversion of hormone precursors into their active form... - The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processingNathan C Rockwell
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California at Berkeley, Room 16, Barker Hall, Berkeley, CA 94720-3202, USA
Trends Biochem Sci 29:80-7. 2004.... - Plasticity of extended subsites facilitates divergent substrate recognition by Kex2 and furinLaura Rozan
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
J Biol Chem 279:35656-63. 2004Yeast Kex2 and human furin are subtilisin-related proprotein convertases that function in the late secretory pathway and exhibit similar though distinguishable patterns of substrate recognition... - Altered processing of the neurotensin/neuromedin N precursor in PC2 knock down mice: a biochemical and immunohistochemical studyPierre Villeneuve
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
J Neurochem 82:783-93. 2002..However, there was no change in the maturation of pro-NT/NN in the brain of mice in which the PC1 gene had been partially inactivated, implying that complete PC1 knock down may be required for loss of function... - Identification of an isoform with an extremely large Cys-rich region of PC6, a Kex2-like processing endoproteaseT Nakagawa
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan
FEBS Lett 327:165-71. 1993..A PC6B transcript was found mainly in the intestine, while PC6A transcripts were in various tissues. These results suggest distinct roles of PC6A and PC6B in endoproteolytic processing of precursor proteins... - Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell linesE 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... - Sequence of the M28 dsRNA: preprotoxin is processed to an alpha/beta heterodimeric protein toxinM J Schmitt
, , Germany
Virology 213:341-51. 1995..While a kex2 delta mutation prevents toxin secretion, secreted toxin retains 20% activity in a kex1 delta mutant. Neither mutation affects immunity... - Characterization of beta-amyloid peptide precursor processing by the yeast Yap3 and Mkc7 proteasesW Zhang
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA
Biochim Biophys Acta 1359:110-22. 1997..They suggest that GPI-linked aspartyl proteases should be investigated as candidate secretases in mammalian tissues... - Shared functions in vivo of a glycosyl-phosphatidylinositol-linked aspartyl protease, Mkc7, and the proprotein processing protease Kex2 in yeastH Komano
Department of Biochemistry, Stanford University School of Medicine, CA 94305 5307, USA
Proc Natl Acad Sci U S A 92:10752-6. 1995..The synergism of mkc7, yap3, and kex2 null mutations argues that Mkc7 and Yap3 are authentic processing enzymes whose functions overlap those of Kex2 in vivo... - Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cellsK Hatsuzawa
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan
J Biol Chem 265:22075-8. 1990..These observations fail to show a role for furin, a Kex2-like mammalian protease, in prohormone processing... - cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinasesN 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... - Structural investigation and kinetic characterization of potential cleavage sites of HIV GP160 by human furin and PC1N Brakch
Institute of Industrial Chemistry, University of Padua, Italy
Biochem Biophys Res Commun 213:356-61. 1995..KAKR decreases R. Furthermore, furin and PC1 are unable to process peptides patterned on the sequence 307-330 of specific viral strains of the gp120 V3 loop... - Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2S P Smeekens
Howard Hughes Medical Institute, Chicago, Illinois
J Biol Chem 265:2997-3000. 1990..We propose that PC2 is a member of a family of mammalian Kex2/subtilisin-like proteases that includes members involved in a number of specific proteolytic events within cells, including the processing of prohormones... - 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 PC2N G Seidah
J A DeSève Laboratories of Biochemical, Clinical Research Institute of Montreal, Quebec, Canada
Mol Endocrinol 5:111-22. 1991..The genes coding for mPC1 and mPC2 map to the murine chromosomes 13 (band 13c) and 2 (2F3-2H2 region), respectively... - Kainic acid increases the expression of the prohormone convertases furin and PC1 in the mouse hippocampusA Meyer
J A DeSève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Brain Res 732:121-32. 1996..Based on colocalization studies and evidence of coordinate expression with NGF and BDNF, we suggest the involvement of furin in processing of proNGF, and of both furin and PC1 in processing of proBDNF... - Structure-function studies on the biosynthesis and bioactivity of the precursor convertase PC2 and the formation of the PC2/7B2 complexS Benjannet
J A de Sève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Canada
FEBS Lett 362:151-5. 1995.... - 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 PS Benjannet
J A DeSève Laboratory of Molecular Neuroendocrinology, Clinical Research Institute of Montreal, Quebec, Canada
Biochem J 294:735-43. 1993..In order to test the possibility that zymogen processing is performed by furin, we co-expressed this convertase with either pro-PC1 or pro-PC2. The data demonstrated the inability of furin to cleave either proenzyme... - Localization of Kex2-like processing endoproteases, furin and PC4, within mouse testis by in situ hybridizationS Torii
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan
FEBS Lett 316:12-6. 1993.... - Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2M K Badman
Department of Human Anatomy, University of Oxford, UK
FEBS Lett 378:227-31. 1996..These data are consistent with processing of proIAPP in beta-cell secretory granules. Abnormal cellular proteolysis associated with type 2 diabetes could contribute to IAPP amyloidosis... - PC8 [corrected], a new member of the convertase familyA Bruzzaniti
St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
Biochem J 314:727-31. 1996.... - Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertasesN G Seidah
J A DeSève Laboratories of Biochemical and Molecular Neuroendocrinology, Clinical Research Institute of Montreal, University of Montreal, Canada
Biochem J 314:951-60. 1996..This comparative study shows that the three candidate mammalian subtilisin/kexin-like convertases identified process proNGF into NGF and that the nature of the final processed products is dependent on the intracellular environment... - Increased proteolytic processing of protein tyrosine phosphatase mu in confluent vascular endothelial cells: the role of PC5, a member of the subtilisin familyM Campan
Cardiovascular Biology Laboratory, Harvard School of Public Health, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
Biochemistry 35:3797-802. 1996..These results indicate that PC5 may have an important role in mediating the cleavage of RPTPmu in response to contact inhibition in HUVEC... - Expression of PC2 and PC1/PC3 in human pheochromocytomasT Konoshita
INSERM Unit 36, College de France, Paris
Mol Cell Endocrinol 99:307-14. 1994..These results demonstrate that functional Kex2-related endoproteases are expressed in human pheochromocytomas and may be involved in the processing of proenkephalin... - Cloning, nucleotide sequence and functions of XPR6, which codes for a dibasic processing endoprotease from the yeast Yarrowia lipolyticaC S Enderlin
Institute of Marine Resources, University of California, Davis 95616
Yeast 10:67-79. 1994..In addition, these structures aggregated forming visible clumps in liquid culture. These growth aberrations were largely eliminated by growing cells in medium at pH 4. Fourth, no mycelial forms were observed regardless of the pH... - Secretogranin III is a sulfated protein undergoing proteolytic processing in the regulated secretory pathwayJ C Holthuis
Department of Animal Physiology, University of Nijmegen, Toernooiveld, 6525 ED Nijmegen, The Netherlands
J Biol Chem 271:17755-60. 1996..We conclude that SgIII is a precursor protein and that the intact molecule can only have an intracellular function, whereas an extracellular role can only be attributed to its cleavage products... - Retroviral envelope glycoprotein processing: structural investigation of the cleavage siteM Moulard
C I M L, Marseille, France, Laboratoire AFMB, IBSM, Marseille, France
Biochemistry 37:4510-7. 1998..Furthermore, we determine and propose a possible structure of the cleavage site which fits to the active site of the modeled furin... - Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. Its testis-specific expressionK Nakayama
Institute of Biological Sciences, University of Tsukuba, Ibaraki, Japan
J Biol Chem 267:5897-900. 1992..These data suggest that PC4 represents a prime candidate for a precursor-processing endoprotease in the testicular germ cells and that its gene expression is regulated during spermatogenesis... - Impaired prohormone convertases in Cpe(fat)/Cpe(fat) miceY Berman
Department of Pharmacology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA
J Biol Chem 276:1466-73. 2001.... - 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.... - Stability and global fold of the mouse prohormone convertase 1 pro-domainM A Tangrea
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville 20850, USA
Biochemistry 40:5488-95. 2001..The structural data help to explain the location of the secondary processing sites in the pro-domains of the PC family, and a consensus sequence for binding to the catalytic domain is proposed... - Endoproteolytic processing of integrin pro-alpha subunits involves the redundant function of furin and proprotein convertase (PC) 5A, but not paired basic amino acid converting enzyme (PACE) 4, PC5B or PC7J C Lissitzky
CNRS UPRESA 6032, Faculte de Pharmacie, 27 Boulevard J Moulin, 13385 Marseille 5 Cedex, France
Biochem J 346:133-8. 2000..In conclusion, these results indicate that integrin alpha-subunit endoproteolytic processing involves the redundant function of furin and PC5A and to a smaller extent PACE4, but not of PC1, PC2, PC5B or PC7...
Research Grants
- THE CRES GENE IN REPRODUCTIONGail Cornwall; Fiscal Year: 2005..abstract_text> ..
- PTHRP 1 to 173 IN CHONDROCYTESRobert 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...
- THE CRES GENE IN REPRODUCTIONGail Cornwall; Fiscal Year: 2007..Also, the newly purchased mass spec will enable on site protein analysis for the studies described above. In short, the environment at TTUHSC is exceptional and will fully support my proposed studies. ..
- ENZYMES INVOLVED IN DYNORPHIN BIOSYNTHESISLakshmi Devi; Fiscal Year: 2002....
- A Multidisciplinary Analysis of Gelsolin Amyloid DiseaseJeffery Kelly; Fiscal Year: 2006..Our long-term goal is to test the amyloid hypothesis in pathology by linking the cell biology and biophysical data to studies on transgenic animals and small molecule inhibitors that prevent misfolding and/or improper processing. ..
- REGULATION OF PROTEIN TRAFFIC IN NEUROENDOCRINE CELLSGary Thomas; Fiscal Year: 2001..cells compartmentalize biochemical reactions has been to study the biochemistry and cell biology of the proprotein convertases (PCS), which catalyze the proteolytic activation of peptide hormones and bioactive proteins in distinct ..
- Mechanisms regulating PKGI proteolysis and modulation of pulmonary SMC phenotypeJesse D Roberts; Fiscal Year: 2010..Studies of the PKGI proteolysis cleavage site and the effect of substrate decoys suggest that proprotein convertases are responsible for PKGI? nuclear localization in SMC...
- Specificity of Subtilisin-like Proprotein ConvertasesJOSEPH SUCIC; Fiscal Year: 2003Subtilisin-like proprotein convertases (SPCs) are endoproteases that function within the secretory pathway of eucaryotic cells...
- Metabolic Modulation of VisionRobert Barlow; Fiscal Year: 2007..abstract_text> ..
- Metabolic Modulation of VisionRobert Barlow; Fiscal Year: 2009..abstract_text> ..
- PRENATAL DIFFERENTIATION OF THE PITUITARY GLANDJohn Pintar; Fiscal Year: 2002....
- Furin and the Etiopathogenesis of UV-Induced Skin CancerAndres J Klein Szanto; Fiscal Year: 2010Furin is a protein processing enzyme of the family of proprotein convertases (PCs), which has a significant role in cancer etiopathogenesis...
- Molecular Target(s) for Interruption of HBV InfectionJisu Li; Fiscal Year: 2009..Determine the contribution of proprotein convertases to DHBV infectivity; and (3)...
- EMBRYONIC SIGNALING REGULATION BY PROPROTEIN CONVERTASESJan L Christian; Fiscal Year: 2010....
- OPIOID PEPTIDE SYNTHESIZING ENZYMESIris Lindberg; Fiscal Year: 2003..abstract_text> ..
- CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETIONRichard Mains; Fiscal Year: 2002..Binding interactions of the pleckstrin homology and src homology 3 domains of Kalirin will be identified. ..
- ProSAAS,A Novel Peptide Substrate of Carboxypeptidase ELloyd Fricker; Fiscal Year: 2005....
- METABOLIC CONSEQUENCES OF A PROHORMONE PROCESSING DEFECTJUERGEN NAGGERT; Fiscal Year: 2002....