title: Mammalian subtilisin-related proteinases in cleavage activation of the paramyxovirus fusion glycoprotein: superiority of furin/PACE to PC2 or PC1/PC3.
abstract: The fusion glycoprotein precursor of Newcastle disease virus is ubiquitously cleaved in the constitutive secretory pathway if it possesses an oligobasic cleavage motif (RRQR/KR), whereas the precursor is refractory to cleavage if the motif is monobasic (GR/KQGR). We examined the cleavage activity of the mammalian subtilisin-related proteinases furin/PACE, PC2, and PC1/PC3, which are thought to be responsible for proprotein processing in either the constitutive (furin/PACE) or the regulated (PC2 and PC1/PC3) secretory pathway, for the viral precursors with different cleavage motifs. Only furin/PACE was fully capable of cleaving the precursors with the oligobasic motif. PC2 and PC1/PC3 were incapable or only partially capable of cleaving at this motif. None of the proteinases cleaved the monobasic motif. These results suggest involvement of furin/PACE in viral protein processing in the constitutive secretory pathway.
authors.affiliation: Radioisotope Center Medical Division, Nagoya University School of Medicine, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Gotoh
authors.forename: Y
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: N M
authors.initials: NM
authors.lastname: Inocencio
authors.forename: E
authors.initials: E
authors.lastname: Esaki
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: P J
authors.initials: PJ
authors.lastname: Barr
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045683:Furin; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000378:metabolism*; D045706:Proprotein Convertase 2; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000494:pharmacology; D013379:Substrate Specificity; D013381:Subtilisins / Q000494:pharmacology*; D014760:Viral Fusion Proteins / Q000187:drug effects*
chemical_list: D011498:Protein Precursors; D014760:Viral Fusion Proteins; D012697:Serine Endopeptidases; D013381:Subtilisins; D045683:Furin; D045706:Proprotein Convertase 2