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Vol. 15, No. 21, pp. 2797-2802, November 1, 2001
1 Department of Cell and Developmental Biology and
2 Vollum Institute, Oregon Health Sciences University,
Portland, Oregon 97201, USA
Proteolytic maturation of proBMP-4 is required to generate an
active signaling molecule. We show that proBMP-4 is cleaved by furin in
a sequential manner. Cleavage at a consensus furin site adjacent to the
mature ligand domain allows for subsequent cleavage at an upstream
nonconsensus furin site within the prodomain. BMP-4 synthesized from
precursor in which the upstream site is noncleavable is less active,
signals at a shorter range, and accumulates at lower levels than does
BMP-4 cleaved from native precursor. Conversely, BMP-4 cleaved from
precursor in which both sites are rapidly cleaved is more active and
signals over a greater range. Differential use of the upstream cleavage
site could provide for tissue-specific regulation of BMP-4 activity and
signaling range.
[Key Words: BMP; proteolytic maturation; furin; signaling range]
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