Ectodomain shedding of furin: kinetics and role of the cysteine-rich region.
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.
Denault
Jean
J
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, J1H 5N4, Sherbrooke, QC, Canada.
Bissonnette
Lyne
L
Longpré
Jean
J
Charest
Gabriel
G
Lavigne
Pierre
P
Leduc
Richard
R
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*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013381:Subtilisins; D045683:Furin; D003545:Cysteine