Secretion of mouse ZP3, the sperm receptor, requires cleavage of its polypeptide at a consensus furin cleavage-site.
The mouse egg extracellular coat, or zona pellucida, consists of three glycoproteins, called mZP1-3. Each glycoprotein possesses a consensus sequence recognized by the furin family of proprotein convertases. Previously, it was reported that mZP2 and mZP3 are cleaved at their consensus furin cleavage-sites located near the C-terminus of the polypeptides [Litscher, E. S., Qi, H., and Wassarman, P. M. (1999) Biochemistry 38, 12280-12287]. Here, use of site-directed mutagenesis of the mZP3 gene and a specific inhibitor of furin-like enzymes revealed that secretion of nascent mZP3 from transfected cells is dependent on cleavage of mZP3 at its consensus furin cleavage-site. The dependence of secretion on cleavage represents a novel function for furin family enzymes.
Williams
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Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029-6574, USA.
Wassarman
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PM
D000581:Amidohydrolases / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018236:Carcinoma, Embryonal; D002460:Cell Line; D016384:Consensus Sequence; D004527:Egg Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045683:Furin; D006801:Humans; D006868:Hydrolysis; D008297:Male; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000138:chemical synthesis / Q000235:genetics; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism*; D013381:Subtilisins / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072216:Zona Pellucida Glycoproteins
C111573:1-oxodecyl-arginyl-valyl-lysyl-arginine chloromethyl ketone; D000590:Amino Acid Chloromethyl Ketones; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; C085706:FLAG peptide; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D013381:Subtilisins; D045683:Furin; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase