ArticleThe Journal of biological chemistry2014
Nodal·Gdf1 heterodimers with bound prodomains enable serum-independent nodal signaling and endoderm differentiation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Kallikrein-8 mediates furin-independent Activin-A precursor processing to stimulate tumor growth in melanoma.Nature communications · 2025Article
- Gdf11 regulates left-right asymmetry development through TGF-β signal.Cell proliferation · 2025Article
- Stepwise release of Activin-A from its inhibitory prodomain is modulated by cysteines and requires furin coexpression to promote melanoma growth.Communications biology · 2024Article
- From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition.Seminars in cancer biology · 2023Review
- Activin-A impairs CD8 T cell-mediated immunity and immune checkpoint therapy response in melanoma.Journal for immunotherapy of cancer · 2022Article
- Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids.Nature communications · 2022Article
- Growth differentiation factor 1-induced tumour plasticity provides a therapeutic window for immunotherapy in hepatocellular carcinoma.Nature communications · 2021Article
- Article
- BMP heterodimers signal via distinct type I receptor class functions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- TGF-β Signaling.Biomolecules · 2020Review
- The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.Development (Cambridge, England) · 2019Article
- ISM1 regulates NODAL signaling and asymmetric organ morphogenesis during development.The Journal of cell biology · 2019Article
- Specificity, versatility, and control of TGF-β family signaling.Science signaling · 2019Review
- A heterodimer formed by bone morphogenetic protein 9 (BMP9) and BMP10 provides most BMP biological activity in plasma.The Journal of biological chemistry · 2018Article
- TGF-β Family Signaling in Early Vertebrate Development.Cold Spring Harbor perspectives in biology · 2018Review
- Article
- Heterodimers reign in the embryo.eLife · 2017Article
- Article
- Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning.eLife · 2017Article
- Maternal Gdf3 is an obligatory cofactor in Nodal signaling for embryonic axis formation in zebrafish.eLife · 2017Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TGFβ family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on the shared co-receptor Cryptic to specify visceral left-right axis asymmetry. We therefore asked whether the functionality of Nodal can be augmented by Gdf1. Because Nodal and Gdf1 coimmunoprecipitate each other, they were predicted to form heterodimers, possibly to facilitate diffusion or to increase the affinity for signaling receptors. Here, we report that Gdf1 suppresses an unexpected dependence of Nodal on serum proteins and that it is critically required for non-autonomous signaling in cells expressing Cryptic. Nodal, Gdf1, and their cleaved propeptides copurified as a heterodimeric low molecular weight complex that stimulated Activin receptor (Acvr) signaling far more potently than Nodal alone. Although heterodimerization with Gdf1 did not increase binding of Nodal to Fc fusions of co-receptors or Acvr extracellular domains, it was essential for soluble Acvr2 to inhibit Nodal signaling. This implies that Gdf1 potentiates Nodal activity by stabilizing a low molecular weight fraction that is susceptible to neutralization by soluble Acvr2. Finally, in differentiating human ES cells, endodermal markers were more efficiently induced by Nodal·Gdf1 than by Nodal, suggesting that Nodal·Gdf1 is an attractive new reagent to direct stem cell differentiation.
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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.