| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Laboratory of Molecular Oncology, Department for Human Genetics, K.U. Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium
1Correspondence: 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. E-mail: john.creemers{at}med.kuleuven.ac.be
The 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. The list of substrates activated by PCs has grown to include neuropeptides, peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules, blood coagulation factors, plasma proteins, viral coat proteins, and bacterial toxins. It has become clear that the PC family plays a crucial role in a variety of physiological processes and is involved in the pathology of diseases such as cancer, viral infection, and Alzheimer’s disease. Recent studies using PC inhibitors have demonstrated their potential as therapeutic targets. Despite the avalanche of in vitro data, the physiological role of individual PCs has remained largely elusive. Recently, however, knockout mouse models have been developed for furin, PC1, PC2, PC4, PC6B, LPC, and PACE4, and human patients with PC1 deficiency have been identified. The phenotypes range from undetectable to early embryonic lethality. The major lesson learned from these studies is that specific PC–substrate pairs do exist, but that there is substantial redundancy for the majority of substrates. To some extent, redundancy may be cell type and even species dependent.—Taylor, N. A., Van De Ven, W. J. M., Creemers, J. W. M. Curbing activation: proprotein convertases in homeostasis and pathology.
Key Words: knockout mice • human patients • viral and bacterial infection • Alzheimer’s disease • inhibitors
This article has been cited by other articles:
|
|
 |
|
  C. Gyamera-Acheampong and M. Mbikay Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review Hum. Reprod. Update, March 1, 2009; 15(2): 237 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Karicherla and J. A. Hobden Nona-D-Arginine Therapy for Pseudomonas aeruginosa Keratitis Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 256 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. V.L. Telugu and J. A. Green Characterization of the Peptidase Activity of Recombinant Porcine Pregnancy-associated Glycoprotein-2 J. Biochem., December 1, 2008; 144(6): 725 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-P. Chen, L.-F. Chen, S.-R. Yang, C.-Y. Chen, C.-C. Ko, G.-D. Chang, and H. Chen Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 2 Biol Reprod, November 1, 2008; 79(5): 815 - 823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Louagie, N. A. Taylor, D. Flamez, A. J. M. Roebroek, N. A. Bright, S. Meulemans, R. Quintens, P. L. Herrera, F. Schuit, W. J. M. Van de Ven, et al. Role of furin in granular acidification in the endocrine pancreas: Identification of the V-ATPase subunit Ac45 as a candidate substrate PNAS, August 26, 2008; 105(34): 12319 - 12324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Remacle, S. A. Shiryaev, E.-S. Oh, P. Cieplak, A. Srinivasan, G. Wei, R. C. Liddington, B. I. Ratnikov, A. Parent, R. Desjardins, et al. Substrate Cleavage Analysis of Furin and Related Proprotein Convertases: A COMPARATIVE STUDY J. Biol. Chem., July 25, 2008; 283(30): 20897 - 20906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Essalmani, A. Zaid, J. Marcinkiewicz, A. Chamberland, A. Pasquato, N. G. Seidah, and A. Prat In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate PNAS, April 15, 2008; 105(15): 5750 - 5755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Rehfeld, J. R. Bundgaard, J. Hannibal, X. Zhu, C. Norrbom, D. F. Steiner, and L. Friis-Hansen 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 Endocrinology, April 1, 2008; 149(4): 1600 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Mayer, J. Hamelin, M.-C. Asselin, A. Pasquato, E. Marcinkiewicz, M. Tang, S. Tabibzadeh, and N. G. Seidah The Regulated Cell Surface Zymogen Activation of the Proprotein Convertase PC5A Directs the Processing of Its Secretory Substrates J. Biol. Chem., January 25, 2008; 283(4): 2373 - 2384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Farooqi, K. Volders, R. Stanhope, R. Heuschkel, A. White, E. Lank, J. Keogh, S. O'Rahilly, and J. W. M. Creemers Hyperphagia and Early-Onset Obesity due to a Novel Homozygous Missense Mutation in Prohormone Convertase 1/3 J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3369 - 3373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wei, K. Hackmann, H. Xu, G. Germino, and F. Qian Characterization of cis-Autoproteolysis of Polycystin-1, the Product of Human Polycystic Kidney Disease 1 Gene J. Biol. Chem., July 27, 2007; 282(30): 21729 - 21737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Freyer, L M Kilpatrick, L A Salamonsen, and G Nie Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium Reproduction, June 1, 2007; 133(6): 1189 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Thomas, C. A. Nechamen, J. E. Mazurkiewicz, M. Muda, S. Palmer, and J. A. Dias Follice-Stimulating Hormone Receptor Forms Oligomers and Shows Evidence of Carboxyl-Terminal Proteolytic Processing Endocrinology, May 1, 2007; 148(5): 1987 - 1995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wheatley and T. Holyoak Differential P1 arginine and lysine recognition in the prototypical proprotein convertase Kex2 PNAS, April 17, 2007; 104(16): 6626 - 6631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. McColl, K. Paavonen, T. Karnezis, N. C. Harris, N. Davydova, J. Rothacker, E. C. Nice, K. W. Harder, S. Roufail, M. L. Hibbs, et al. Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2 FASEB J, April 1, 2007; 21(4): 1088 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. W. Smolenaars, O. Madsen, K. W. Rodenburg, and D. J. Van der Horst Molecular diversity and evolution of the large lipid transfer protein superfamily J. Lipid Res., March 1, 2007; 48(3): 489 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Thimon, M. Belghazi, J.-L. Dacheux, and J.-L. Gatti Analysis of furin ectodomain shedding in epididymal fluid of mammals: demonstration that shedding of furin occurs in vivo. Reproduction, December 1, 2006; 132(6): 899 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Scamuffa, F. Calvo, M. Chretien, N. G. Seidah, and A.-M. Khatib Proprotein convertases: lessons from knockouts FASEB J, October 1, 2006; 20(12): 1954 - 1963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Goldman, R. Hackenmiller, T. Nakayama, S. Sopory, C. Wong, H. Kulessa, and J. L. Christian Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue-specific loss of activity Development, May 15, 2006; 133(10): 1933 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Limaye, V. Koya, M. Samsam, and H. Daniell Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system FASEB J, May 1, 2006; 20(7): 959 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. M. Creemers, L. E. Pritchard, A. Gyte, P. Le Rouzic, S. Meulemans, S. L. Wardlaw, X. Zhu, D. F. Steiner, N. Davies, D. Armstrong, et al. Agouti-Related Protein Is Posttranslationally Cleaved by Proprotein Convertase 1 to Generate Agouti-Related Protein (AGRP)83-132: Interaction between AGRP83-132 and Melanocortin Receptors Cannot Be Influenced by Syndecan-3 Endocrinology, April 1, 2006; 147(4): 1621 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rabah, D. Gauthier, B. C. Wilkes, D. J. Gauthier, and C. Lazure Single Amino Acid Substitution in the PC1/3 Propeptide Can Induce Significant Modifications of Its Inhibitory Profile toward Its Cognate Enzyme J. Biol. Chem., March 17, 2006; 281(11): 7556 - 7567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Essalmani, J. Hamelin, J. Marcinkiewicz, A. Chamberland, M. Mbikay, M. Chretien, N. G. Seidah, and A. Prat Deletion of the Gene Encoding Proprotein Convertase 5/6 Causes Early Embryonic Lethality in the Mouse Mol. Cell. Biol., January 1, 2006; 26(1): 354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Capurro, W. Shi, S. Sandal, and J. Filmus Processing by Convertases Is Not Required for Glypican-3-induced Stimulation of Hepatocellular Carcinoma Growth J. Biol. Chem., December 16, 2005; 280(50): 41201 - 41206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tang, A. Mikhailik, I. Pauli, L. C. Giudice, A. T. Fazelabas, S. Tulac, D. D. Carson, D. G. Kaufman, C. Barbier, J. W. M. Creemers, et al. Decidual Differentiation of Stromal Cells Promotes Proprotein Convertase 5/6 Expression and Lefty Processing Endocrinology, December 1, 2005; 146(12): 5313 - 5320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Bassi, R. Lopez De Cicco, J. Cenna, S. Litwin, E. Cukierman, and A. J.P. Klein-Szanto PACE4 Expression in Mouse Basal Keratinocytes Results in Basement Membrane Disruption and Acceleration of Tumor Progression Cancer Res., August 15, 2005; 65(16): 7310 - 7319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Ustach and H.-R. C. Kim Platelet-Derived Growth Factor D Is Activated by Urokinase Plasminogen Activator in Prostate Carcinoma Cells Mol. Cell. Biol., July 15, 2005; 25(14): 6279 - 6288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jansen, C. Stefan, J. W. M. Creemers, E. Waelkens, A. Van Eynde, W. Stalmans, and M. Bollen Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D J. Cell Sci., July 15, 2005; 118(14): 3081 - 3089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gauster, A. Hrzenjak, K. Schick, and S. Frank Endothelial lipase is inactivated upon cleavage by the members of the proprotein convertase family J. Lipid Res., May 1, 2005; 46(5): 977 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Nie, Y. Li, M. Wang, Y. X. Liu, J. K. Findlay, and L. A. Salamonsen Inhibiting Uterine PC6 Blocks Embryo Implantation: An Obligatory Role for a Proprotein Convertase in Fertility Biol Reprod, April 1, 2005; 72(4): 1029 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Bauskin, D. A. Brown, S. Junankar, K. K. Rasiah, S. Eggleton, M. Hunter, T. Liu, D. Smith, T. Kuffner, G. J. Pankhurst, et al. The Propeptide Mediates Formation of Stromal Stores of PROMIC-1: Role in Determining Prostate Cancer Outcome Cancer Res., March 15, 2005; 65(6): 2330 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. W. Smolenaars, M. A. M. Kasperaitis, P. E. Richardson, K. W. Rodenburg, and D. J. Van der Horst Biosynthesis and secretion of insect lipoprotein: involvement of furin in cleavage of the apoB homolog, apolipophorin-II/I J. Lipid Res., March 1, 2005; 46(3): 412 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.L. Juengel and K.P. McNatty The role of proteins of the transforming growth factor-{beta} superfamily in the intraovarian regulation of follicular development Hum. Reprod. Update, March 1, 2005; 11(2): 144 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Maxwell, E. A. Fisher, and J. L. Breslow Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment PNAS, February 8, 2005; 102(6): 2069 - 2074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Okada, G. Nie, and L. A. Salamonsen Requirement for Proprotein Convertase 5/6 during Decidualization of Human Endometrial Stromal Cells in Vitro J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1028 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Birsoy, L. Berg, P. H. Williams, J. C. Smith, C. C. Wylie, J. L. Christian, and J. Heasman XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGF{beta} proteins in Xenopus development Development, February 1, 2005; 132(3): 591 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kawalec, J. Potempa, J. L. Moon, J. Travis, and B. E. Murray Molecular Diversity of a Putative Virulence Factor: Purification and Characterization of Isoforms of an Extracellular Serine Glutamyl Endopeptidase of Enterococcus faecalis with Different Enzymatic Activities J. Bacteriol., January 1, 2005; 187(1): 266 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nedvetzki, E. Gonen, N. Assayag, R. Reich, R. O. Williams, R. L. Thurmond, J.-F. Huang, B. A. Neudecker, F.-S. Wang, E. A. Turley, et al. RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: A different interpretation of redundancy PNAS, December 28, 2004; 101(52): 18081 - 18086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. M. Roebroek, N. A. Taylor, E. Louagie, I. Pauli, L. Smeijers, A. Snellinx, A. Lauwers, W. J. M. Van de Ven, D. Hartmann, and J. W. M. Creemers Limited Redundancy of the Proprotein Convertase Furin in Mouse Liver J. Biol. Chem., December 17, 2004; 279(51): 53442 - 53450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Benjannet, D. Rhainds, R. Essalmani, J. Mayne, L. Wickham, W. Jin, M.-C. Asselin, J. Hamelin, M. Varret, D. Allard, et al. NARC-1/PCSK9 and Its Natural Mutants: ZYMOGEN CLEAVAGE AND EFFECTS ON THE LOW DENSITY LIPOPROTEIN (LDL) RECEPTOR AND LDL CHOLESTEROL J. Biol. Chem., November 19, 2004; 279(47): 48865 - 48875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Kibler, A. Miyazato, V. S. R. K. Yedavalli, A. I. Dayton, B. L. Jacobs, G. Dapolito, S.-j. Kim, and K.-T. Jeang Polyarginine Inhibits gp160 Processing by Furin and Suppresses Productive Human Immunodeficiency Virus Type 1 Infection J. Biol. Chem., November 19, 2004; 279(47): 49055 - 49063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dubuc, A. Chamberland, H. Wassef, J. Davignon, N. G. Seidah, L. Bernier, and A. Prat Statins Upregulate PCSK9, the Gene Encoding the Proprotein Convertase Neural Apoptosis-Regulated Convertase-1 Implicated in Familial Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1454 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wang, M. Tortorella, K. England, A.-M. Malfait, G. Thomas, E. C. Arner, and D. Pei Proprotein Convertase Furin Interacts with and Cleaves Pro-ADAMTS4 (Aggrecanase-1) in the trans-Golgi Network J. Biol. Chem., April 9, 2004; 279(15): 15434 - 15440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D'Anjou, L. J. Bergeron, N. B. Larbi, I. Fournier, M. Salzet, J.-P. Perreault, and R. Day Silencing of SPC2 Expression Using an Engineered {delta} Ribozyme in the Mouse {beta}TC-3 Endocrine Cell Line J. Biol. Chem., April 2, 2004; 279(14): 14232 - 14239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. De Cat, S.-Y. Muyldermans, C. Coomans, G. Degeest, B. Vanderschueren, J. Creemers, F. Biemar, B. Peers, and G. David Processing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements J. Cell Biol., November 10, 2003; 163(3): 625 - 635. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
