BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development
| Autor: | François Jean, Gary Thomas, Yanzhen Cui, Jan L. Christian |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Embryo
Nonmammalian animal structures Xenopus Bone Morphogenetic Protein 4 Xenopus Proteins Bone morphogenetic protein General Biochemistry Genetics and Molecular Biology Mesoderm Serine Ectoderm Animals Cell Lineage Subtilisins Protein Precursors Molecular Biology Furin DNA Primers Base Sequence General Immunology and Microbiology biology Hydrolysis General Neuroscience biology.organism_classification Proprotein convertase Biochemistry Bone morphogenetic protein 4 alpha 1-Antitrypsin Bone Morphogenetic Proteins embryonic structures Proprotein Convertase 5 biology.protein Ectopic expression Proprotein Convertases Protein Processing Post-Translational Research Article Signal Transduction |
| Zdroj: | The EMBO Journal. 17:4735-4743 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/17.16.4735 |
| Popis: | Bone morphogenetic protein-4 (BMP-4) is a multifunctional developmental regulator. BMP-4 is synthesized as an inactive precursor that is proteolytically activated by cleavage following the amino acid motif -Arg-Ser-Lys-Arg-. Very little is known about processing and secretion of BMPs. The proprotein convertases (PCs) are a family of seven structurally related serine endoproteases, at least one of which, furin, cleaves after the amino acid motif -Arg-X-Arg/Lys-Arg-. To examine potential roles of PCs during embryonic development we have misexpressed a potent protein inhibitor of furin, alpha1-antitrypsin Portland (alpha1-PDX) in early Xenopus embryos. Ectopic expression of alpha1-PDX phenocopies the effect of blocking endogenous BMP activity, leading to dorsalization of mesoderm and direct neural induction. alpha1-PDX-mediated neural induction can be reversed by co-expression of downstream components of the BMP-4 signaling pathway. Thus, alpha1-PDX can block BMP activity upstream of receptor binding, suggesting that it inhibits an endogenous BMP-4 convertase(s). Consistent with this hypothesis, alpha1-PDX prevents cleavage of BMP-4 in an oocyte translation assay. Using an in vitro digestion assay, we demonstrate that four members of the PC family have the ability to cleave BMP-4, but of these, only furin and PC6B are sensitive to alpha1-PDX. These studies provide the first in vivo evidence that furin and/or PC6 proteolytically activate BMP-4 during vertebrate embryogenesis. |
| Databáze: | OpenAIRE |
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