ArticleThe Journal of biological chemistry2009
Site-specific cleavage of BMP4 by furin, PC6, and PC7.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.Human molecular genetics · 2011Pooled it
- PCSK7 genotype modifies effect of a weight-loss diet on 2-year changes of insulin resistance: the POUNDS LOST trial.Diabetes care · 2015Trial
- TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER triage checkpoint for BMP4/Dpp.Cell reports · 2026Article
- TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER Triage Checkpoint for BMP4/Dpp.bioRxiv : the preprint server for biology · 2025Article
- Macrophage regulation of tumor cell dormancy and the dormant niche: an overview in solid tumors.Cancer metastasis reviews · 2025Review
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- The TGF-β superfamily as potential therapeutic targets in pancreatic cancer.Frontiers in oncology · 2024Review
- Review
- BMP-4 Extraction from Extracellular Matrix and Analysis of Heparin-Binding Properties.Molecular biotechnology · 2022Article
- Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Bone Morphogenetic Proteins Shape TFrontiers in immunology · 2022Review
- Bone Morphogenetic Protein 2/4 in Mollusk, Haliotis diversicolor: Its Expression and Osteoinductive Function In Vitro.Marine biotechnology (New York, N.Y.) · 2021Article
- Deciphering and reconstitution of positional information in the human brain development.Cell regeneration (London, England) · 2021Review
- Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos.Journal of visualized experiments : JoVE · 2021Article
- Bone Morphogenic Protein Signaling and Melanoma.Current treatment options in oncology · 2021Review
- Article
- A Potential Role of Bone Morphogenetic Protein 7 in Shell Formation and Growth in the Razor ClamFrontiers in physiology · 2020Article
- Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.PloS one · 2019Article
- Analysis of novel domain-specific mutations in the zebrafishJournal of genetics · 2018Article
- Positive selection drives the evolution of endocrine regulatory bone morphogenetic protein system in mammals.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Bone morphogenetic proteins (BMPs) require proteolytic activation by members of the proprotein convertase (PC) family. Pro-BMP4 is initially cleaved at a site adjacent to the mature ligand domain (S1) and then at an upstream site (S2) within the prodomain. Cleavage at the S2 site, which appears to occur in a tissue-specific fashion, regulates the activity and signaling range of mature BMP4. To test the hypothesis that tissue-specific cleavage of pro-BMP4 is regulated by differential expression of a site-specific protease, we identified the PCs that cleave each site in vivo. In Xenopus oocytes, furin and PC6 function redundantly to cleave both the S1 and S2 sites of pro-BMP4, as evidenced by the results of antisense-mediated gene knockdown and the use of the furin- and PC6-selective inhibitor alpha(1)-PDX. By contrast, alpha(1)-PDX blocked cleavage of the S2 but not the S1 site of pro-BMP4 in embryos, suggesting the existence of a developmentally regulated S1 site-specific convertase. This protease is likely to be PC7 based on knowledge of its required substrate cleavage motif and resistance to alpha(1)-PDX. Consistent with this prediction, an alpha(1)-PDX variant engineered to target PC7, in addition to furin and PC6, completely inhibited cleavage of BMP4 in oocytes and embryos. Further studies showed that pc7 transcripts are expressed and polyadenylated, and that the PC7 precursor protein undergoes efficient autocatalytic activation in both oocytes and embryos. These results suggest that PC7, or a convertase with similar substrate specificity, functions to selectively cleave the S1 site of pro-BMP4 in a developmentally regulated fashion.
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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.