ArticleProceedings of the National Academy of Sciences of the United States of America2015
The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
31 citing papers in PubMed, 49 citations in OpenAlex.
- Reduction of primary tumor growth and metastasis in models of triple-negative breast cancer following tilorone administration via type I interferon signaling.Breast cancer research : BCR · 2026Article
- Effects of Bone Morphogenetic Protein Agonist Small Molecule, SB4, on Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells.Journal of bone metabolism · 2026Article
- Muscle-Derived BMP4 Regulates Morphology and Function of Endplates on Extrafusal and Intrafusal Muscle Fibers in Adult Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Article
- MuSK Regulates Neuromuscular Junction Nav1.4 Localization and Excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The prodomain of bone morphogenetic protein 2 promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers.The Journal of biological chemistry · 2024Article
- TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen.PLoS genetics · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- TGF-β Ligand Cross-Subfamily Interactions in the Response ofbioRxiv : the preprint server for biology · 2023Article
- Formation and characterization of BMP2/GDF5 and BMP4/GDF5 heterodimers.BMC biology · 2023Article
- Protection of the Prodomain α1-Helix Correlates with Latency in the Transforming Growth Factor-β Family.Journal of molecular biology · 2022Article
- Molecular Mechanisms of AMH Signaling.Frontiers in endocrinology · 2022Review
- Targeting Stress Erythropoiesis Pathways in Cancer.Frontiers in physiology · 2022Review
- Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos.Journal of visualized experiments : JoVE · 2021Article
- BMP heterodimers signal via distinct type I receptor class functions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- BMP Signaling: Lighting up the Way for Embryonic Dorsoventral Patterning.Frontiers in cell and developmental biology · 2021Review
- Rare heterozygous GDF6 variants in patients with renal anomalies.European journal of human genetics : EJHG · 2020Article
- GDF6-CD99 Signaling Regulates Src and Ewing Sarcoma Growth.Cell reports · 2020Article
- Review
- Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) are morphogens that signal as either homodimers or heterodimers to regulate embryonic development and adult homeostasis. BMP4/7 heterodimers exhibit markedly higher signaling activity than either homodimer, but the mechanism underlying the enhanced activity is unknown. BMPs are synthesized as inactive precursors that dimerize and are then cleaved to generate both the bioactive ligand and prodomain fragments, which lack signaling activity. Our study reveals a previously unknown requirement for the BMP4 prodomain in promoting heterodimer activity. We show that BMP4 and BMP7 precursor proteins preferentially or exclusively form heterodimers when coexpressed in vivo. In addition, we show that the BMP4 prodomain is both necessary and sufficient for generation of stable heterodimeric ligands with enhanced activity and can enable homodimers to signal in a context in which they normally lack activity. Our results suggest that intrinsic properties of the BMP4 prodomain contribute to the relative bioactivities of homodimers versus heterodimers in vivo. These findings have clinical implications for the use of BMPs as regenerative agents for the treatment of bone injury and disease.
Indexed as
Identifiers
What OpenQuestion holds
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.