Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cells.
We have cloned and sequenced a mouse cDNA encoding the 793-residue amino acid sequence of furin, which is a protein homologous to the yeast Kex2 protease. The entire sequence is 94% identical to that of human furin, and it contains the 289-residue sequence of the subtilisin-like catalytic domain. Within this region, 99, 64, and 53% of the amino acids are identical to those of human furin, human PC2 (the other mammalian Kex2-like protein), and yeast Kex2, respectively. It has been proposed that furin is a mammalian prohormone processing enzyme which cleaves precursors at paired basic amino acids, based on the fact that the Kex2 protease is responsible for processing of alpha-mating factor and killer toxin precursors at dibasic sites. However, Northern blot analysis has revealed that a furin mRNA transcript is present in all tested mouse tissues and culture cell lines, including those known not to process prohormones. Moreover, when furin and a prohormone, prorenin, have been coexpressed in mammalian cells by DNA transfection, no processing has been observed. These observations fail to show a role for furin, a Kex2-like mammalian protease, in prohormone processing.
Hatsuzawa
K
K
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
Hosaka
M
M
Nakagawa
T
T
Nagase
M
M
Shoda
A
A
Murakami
K
K
Nakayama
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004792:Enzyme Precursors / Q000235:genetics*; D045683:Furin; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D043484:Proprotein Convertases; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012083:Renin / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics*; D013381:Subtilisins / Q000235:genetics*
D004792:Enzyme Precursors; D015345:Oligonucleotide Probes; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D011505:Protein-Tyrosine Kinases; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae; D045683:Furin; D012083:Renin