ArticleMolecular biology of the cell2004
Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 107 citations in OpenAlex.
- TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER triage checkpoint for BMP4/Dpp.Cell reports · 2026Article
- Article
- The prodomain of bone morphogenetic protein 2 promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers.The Journal of biological chemistry · 2024Article
- Lack of evidence that fibrillin1 regulates bone morphogenetic protein 4 activity in kidney or lung.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Protection of the Prodomain α1-Helix Correlates with Latency in the Transforming Growth Factor-β Family.Journal of molecular biology · 2022Article
- Local BMP signaling: A sensor for synaptic activity that balances synapse growth and function.Current topics in developmental biology · 2022Review
- Molecular Evolution of Transforming Growth Factor-β (TGF-β) Gene Family and the Functional Characterization of Lamprey TGF-β2.Frontiers in immunology · 2022Article
- Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos.Journal of visualized experiments : JoVE · 2021Article
- Differential compartmentalization of BMP4/NOGGIN requires NOGGIN trans-epithelial transport.Developmental cell · 2021Article
- Article
- Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b.PLoS genetics · 2019Article
- Investigation on the processing and improving the cleavage efficiency of furin cleavage sites in Pichia pastoris.Microbial cell factories · 2018Article
- Domains with highest heparan sulfate-binding affinity reside at opposite ends in BMP2/4The Journal of biological chemistry · 2018Article
- Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.The Journal of biological chemistry · 2017Article
- Article
- Parallel Activin and BMP signaling coordinates R7/R8 photoreceptor subtype pairing in the stochasticeLife · 2017Article
- Agonists and Antagonists of TGF-β Family Ligands.Cold Spring Harbor perspectives in biology · 2016Review
- Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis.Circulation research · 2016Review
- Bone Morphogenetic Protein 4 Signalling in Neural Stem and Progenitor Cells during Development and after Injury.Stem cells international · 2016Review
- The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pro bone morphogenetic protein-4 (BMP-4) is initially cleaved at a consensus furin motif adjacent to the mature ligand domain (the S1 site), and this allows for subsequent cleavage at an upstream motif (the S2 site). Previous studies have shown that S2 cleavage regulates the activity and signaling range of mature BMP-4, but the mechanism by which this occurs is unknown. Here, we show that the pro- and mature domains of BMP-4 remain noncovalently associated after S1 cleavage, generating a complex that is targeted for rapid degradation. Degradation requires lysosomal and proteosomal function and is enhanced by interaction with heparin sulfate proteoglycans. Subsequent cleavage at the S2 site liberates mature BMP-4 from the prodomain, thereby stabilizing the protein. We also show that cleavage at the S2, but not the S1 site, is enhanced at reduced pH, consistent with the possibility that the two cleavages occur in distinct subcellular compartments. Based on these results, we propose a model for how cleavage at the upstream site regulates the activity and signaling range of mature BMP-4 after it has been released from the prodomain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.