ArticleThe Journal of biological chemistry2016
Transforming Growth Factor-β Family Ligands Can Function as Antagonists by Competing for Type II Receptor Binding.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Interleukin-1 and Transforming Growth Factor Beta: Commonly Opposing, but Sometimes Supporting, Master Regulators of the Corneal Wound Healing Response to Injury.Investigative ophthalmology & visual science · 2021Pooled it
- GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial.Nature communications · 2025Trial
- Humans with function-disrupting variants in the myostatin gene (MSTN) have increased skeletal muscle mass and strength, and less adiposity.Nature communications · 2026Article
- Article
- Genetic and functional characterization of AMH Signaling in Zebrafish - Evidence for Roles of Amh-Bmpr2a-Bmpr1bb Pathway in Controlling Gonadal Homeostasis.PLoS genetics · 2026Article
- Codon-optimized human Smad7 gene therapy enhances skeletal muscle mass and function in a murine model of Duchenne muscular dystrophy.Gene therapy · 2026Article
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- Endoglin as a BMP9 co-receptor in vascular endothelial cells: prodomain displacement and TGFBRII recruitment.Nature communications · 2025Article
- Disrupting BMP/TGF-β Signaling: Modulation of AQP1 and TGFB1 in Human Pulmonary Microvascular Endothelial Cells.Comprehensive Physiology · 2025Article
- Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.Cancer cell · 2025Article
- Molecular mechanism of Activin receptor inhibition by DLK1.Nature communications · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3.Nature communications · 2025Article
- GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates.Nature communications · 2025Article
- ActRII or BMPR ligands inhibit skeletal myoblast differentiation, and BMPs promote heterotopic ossification in skeletal muscles in mice.Skeletal muscle · 2025Article
- Targeting Soluble TGF-β Factors: Advances in Precision Therapy for Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2024Review
- Stepwise release of Activin-A from its inhibitory prodomain is modulated by cysteines and requires furin coexpression to promote melanoma growth.Communications biology · 2024Article
- Effect of sotatercept on circulating proteomics in pulmonary arterial hypertension.The European respiratory journal · 2024Article
- Discovery of Two Highly Selective Structurally Orthogonal Chemical Probes for Activin Receptor-like Kinases 1 and 2.Journal of medicinal chemistry · 2024Article
- Bone morphogenetic protein signalling in pulmonary arterial hypertension: revisiting the BMPRII connection.Biochemical Society transactions · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor-β (TGF-β) family ligands are pleiotropic cytokines. Their physiological activities are not determined by a simple coupling of stimulus and response, but depend critically on context, i.e. the interplay of receptors, ligands, and regulators that form the TGF-β signal transduction system of a cell or tissue. How these different components combine to regulate signaling activities remains poorly understood. Here, we describe a ligand-mediated mechanism of signaling regulation. Based on the observation that the type II TGF-β family receptors ActRIIA, ActRIIB, and BMPRII interact with a large group of overlapping ligands at overlapping epitopes, we hypothesized high affinity ligands compete with low affinity ligands for receptor binding and signaling. We show activin A and other high affinity ligands directly inhibited signaling by the low affinity ligands BMP-2, BMP-7, and BMP-9. We demonstrate activin A functions as a competitive inhibitor that blocks the ligand binding epitope on type II receptors. We propose binding competition and signaling antagonism are integral functions of the TGF-β signal transduction system. These functions could help explain how activin A modulates physiological signaling during extraordinary cellular responses, such as injury and wound healing, and how activin A could elicit disease phenotypes such as cancer-related muscle wasting and fibrosis.
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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.