title: Ectodomain shedding of furin: kinetics and role of the cysteine-rich region.
abstract: Furin, a member of the subtilisin-like pro-protein convertase family, is a type I membrane protein that undergoes ectodomain shedding. Metabolic labeling of cells stably expressing furin demonstrated that the shed form of furin is detected after 30 min. Moreover, sequence analysis revealed that specific residues of the cysteine-rich region of furin aligned with those of tumor necrosis factor receptor, which is also shed. Introduction within furin's cysteine-rich region of mutations that impair TNFR1 shedding also abolished furin shedding. Our results show that shedding of furin occurs rapidly and further suggest that specific cysteine residues may impart a conformation to the enzyme, thereby affecting its susceptibility to proteolysis.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, J1H 5N4, Sherbrooke, QC, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Denault
authors.forename: Lyne
authors.initials: L
authors.lastname: Bissonnette
authors.forename: Jean
authors.initials: J
authors.lastname: Longpré
authors.forename: Gabriel
authors.initials: G
authors.lastname: Charest
authors.forename: Pierre
authors.initials: P
authors.lastname: Lavigne
authors.forename: Richard
authors.initials: R
authors.lastname: Leduc
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry; D001483:Base Sequence; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry*; D045683:Furin; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D017354:Point Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry; D047888:Receptors, Tumor Necrosis Factor, Type I; D016415:Sequence Alignment; D013381:Subtilisins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013381:Subtilisins; D045683:Furin; D003545:Cysteine