Human fur gene encodes a yeast KEX2-like endoprotease that cleaves pro-beta-NGF in vivo.
Extracts from BSC-40 cells infected with vaccinia recombinants expressing either the yeast KEX2 prohormone endoprotease or a human structural homologue (fur gene product) contained an elevated level of a membrane-associated endoproteolytic activity that could cleave at pairs of basic amino acids (-LysArg- and -ArgArg-). The fur-directed activity (furin) shared many properties with Kex2p including activity at pH 7.3 and a requirement for calcium. By using antifurin antibodies, immunoblot analysis detected two furin translation products (90 and 96 kD), while immunofluorescence indicated localization to the Golgi apparatus. Coexpression of either Kex2p or furin with the mouse beta-nerve growth factor precursor (pro-beta-NGF) resulted in greatly enhanced conversion of the precursor to mature nerve growth factor. Thus, the sequence homology shared by furin and the yeast KEX2 prohormone processing enzyme is reflected by significant functional homology both in vitro and in vivo.
Bresnahan
P A
PA
Vollum Institute, Oregon Health Sciences University, Portland 97201-3098.
Leduc
R
R
Thomas
L
L
Thorner
J
J
Gibson
H L
HL
Brake
A J
AJ
Barr
P J
PJ
Thomas
G
G
D000595:Amino Acid Sequence; D010450:Endopeptidases / Q000235:genetics* / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics; D045683:Furin; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D012697:Serine Endopeptidases / Q000502:physiology; D013379:Substrate Specificity; D013381:Subtilisins / Q000235:genetics* / Q000502:physiology*
D005656:Fungal Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011498:Protein Precursors; D029701:Saccharomyces cerevisiae Proteins; D010450:Endopeptidases; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae; D045683:Furin