ArticleScientific reports2016
Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 95 citations in OpenAlex.
- Pharmacological Inhibition of Small Extracellular Vesicle Secretion by ALK5i SD-208 via Lysosomal Rerouting of CD63+ Compartments.Journal of extracellular vesicles · 2026Article
- Loss of Zmiz1 in Mice Leads to Impaired Cortical Development and Autistic-Like Behaviors.Biological psychiatry · 2026Article
- E3 ligase SMURF2 promotes adipogenesis and improves obesity complications by suppressing TGF-β signaling.Journal of lipid research · 2026Article
- Far Infrared Radiation Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice via Modulation of the p53/TGF-β Signaling Pathway.International journal of molecular sciences · 2026Article
- Palmitoylation Induced Activation of SMAD3 Exacerbates Colitis by Promoting Tissue-resident Memory T Cells Differentiation.Inflammation · 2026Article
- Inhibition of TGF-beta signaling protects from alpha-synuclein induced toxicity.Cell death discovery · 2025Article
- Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromes.The Journal of clinical investigation · 2025Article
- Article
- Preclinical validation of TGFβ inhibitors as a novel therapeutic strategy for post-traumatic heterotopic ossification.Scientific reports · 2025Article
- Expression Patterns of SMAD1-8 in the Peripheral Facial Nerve Following Compressive Nerve Injury or Axotomy.International journal of molecular sciences · 2025Article
- Review
- Association of genetic variants, protein domains, and phenotypes in the ZMIZ1 syndromic neurodevelopmental disorder.Frontiers in neuroscience · 2025Article
- Acetylation-regulated DUSP1 deficiency contributes to renal fibrosis progression.Theranostics · 2025Article
- Exploring Smad5: a review to pave the way for a deeper understanding of the pathobiology of common respiratory diseases.Molecular medicine (Cambridge, Mass.) · 2024Review
- Computational Identification of Milk Trait Regulation Through Transcription Factor Cooperation in Murciano-Granadina Goats.Biology · 2024Article
- Article
- Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy.Yonsei medical journal · 2024Article
- Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway.Biomolecules & therapeutics · 2024Article
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Analysis of Smad3 in the modulation of stromal extracellular matrix proteins in corneal scarring after alkali injury.Molecular vision · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.
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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.