PubMed Journals: Biochem J
Source: PMID: 11237874
⇦ ⇨ Biochem J. 2001 Mar 15;354(Pt 3):689-95.
'Shed' furin: mapping of the cleavage determinants
and identification of its C-terminus.
Plaimauer B(1), Mohr G, Wernhart W, Himmelspach
M, Dorner F, Schlokat U.
(1) Biomedical Research Center, Hyland-Immuno
Division, Baxter Healthcare, Uferstr. 15,
2304 Orth/Donau, Austria.
The human endoprotease furin is involved
in the proteolytic maturation of the precursor
molecules of a wide variety of bioactive
proteins. Despite its localization in the
membranes of the trans-Golgi system by means
of a transmembrane domain, it has repeatedly
been reported to form a C-terminally truncated,
naturally secreted form referred to as 'shed'
furin. In order to identify the cleavage
site, internal deletion mutants of increasing
size, N-terminal to Leu(708), and subsequently
individual amino acid substitutions were
introduced, and Arg(683) was identified
as the prime determinant for shedding. MS
analysis determined Ser(682) as the C-terminus
of shed furin, suggesting that monobasic
cleavage may occur N-terminal to Arg(683).
Alteration of Arg(683) directs the shedding
mechanism to alternative cleaving sites
PMCID: PMC1221701 PMID: 11237874 [Indexed