Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
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.
???displayArticle.pubmedLink???
11691831
???displayArticle.pmcLink???PMC312809 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Anderson,
Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage.
1997, Pubmed
Anderson,
Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage.
1997,
Pubmed
Aono,
Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer.
1995,
Pubmed
,
Xenbase
Cho,
BMPs, Smads and metalloproteases: extracellular and intracellular modes of negative regulation.
1998,
Pubmed
Christian,
Overexpression of wild-type and dominant negative mutant vimentin subunits in developing Xenopus embryos.
1990,
Pubmed
,
Xenbase
Christian,
Can't get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-beta family signals.
1999,
Pubmed
,
Xenbase
Constam,
Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases.
1999,
Pubmed
Cui,
BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development.
1998,
Pubmed
,
Xenbase
Dosch,
Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus.
1997,
Pubmed
,
Xenbase
Evan,
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
1985,
Pubmed
,
Xenbase
Faure,
Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development.
2000,
Pubmed
,
Xenbase
Gray,
Requirement for activin A and transforming growth factor--beta 1 pro-regions in homodimer assembly.
1990,
Pubmed
Hawley,
Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction.
1995,
Pubmed
,
Xenbase
Hogan,
Bone morphogenetic proteins: multifunctional regulators of vertebrate development.
1996,
Pubmed
Horton,
Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction.
1990,
Pubmed
Jones,
Signalling by TGF-beta family members: short-range effects of Xnr-2 and BMP-4 contrast with the long-range effects of activin.
1996,
Pubmed
,
Xenbase
Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase
Kessler,
Induction of dorsal mesoderm by soluble, mature Vg1 protein.
1995,
Pubmed
,
Xenbase
Kurata,
Visualization of endogenous BMP signaling during Xenopus development.
2001,
Pubmed
,
Xenbase
Molloy,
Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen.
1992,
Pubmed
Nakayama,
Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning.
1998,
Pubmed
,
Xenbase
Nakayama,
Regulation of BMP/Dpp signaling during embryonic development.
2000,
Pubmed
,
Xenbase
Neumann,
Morphogens and pattern formation.
1997,
Pubmed
,
Xenbase
Shinde,
Intramolecular chaperones: polypeptide extensions that modulate protein folding.
2000,
Pubmed
Steiner,
The proprotein convertases.
1998,
Pubmed
Zhou,
Proteolytic processing in the secretory pathway.
1999,
Pubmed