ArticleThe Journal of biological chemistry2009
Transforming growth factor-{beta}-inducible phosphorylation of Smad3.
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 87 papers.
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Who cites it
87 citing papers in PubMed, 142 citations in OpenAlex.
- Article
- Induction of mitochondrial fission and mtDNA leakage via the Smad3/Drp1 axis by PEDV infection activates the TLR9/NF-κB/IL-1β inflammatory pathway.Virologica Sinica · 2026Article
- High-throughput screening of ALS patient iPSC-derived spinal motor neurons identifies novel compounds that increase neurofilament light chain expression.SLAS discovery : advancing life sciences R & D · 2026Article
- Identifying regulators of aged fibroblast activation in 3D tissue models.Scientific reports · 2025Article
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- TGFβ in Pancreas and Colorectal Cancer: Opportunities to Overcome Therapeutic Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Article
- Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-β signaling responses in ovarian cancer.Cell communication and signaling : CCS · 2024Article
- Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.World journal of gastrointestinal oncology · 2024Article
- Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion.Cell death & disease · 2023Article
- A novel pathogenic variant located just upstream of the C-terminal Ser423-X-Ser425 phosphorylation motif in SMAD3 causing Loeys-Dietz syndrome.Molecular genetics & genomic medicine · 2023Article
- Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures.NPJ Regenerative medicine · 2023Article
- Review
- Opposing functions of circadian protein DBP and atypical E2F family E2F8 in anti-tumor Th9 cell differentiation.Nature communications · 2022Article
- Natural Adrenocorticotropic Hormone (ACTH) Relieves Acute Inflammation in Gout Patients by Changing the Function of Macrophages.Journal of healthcare engineering · 2022Article
- A dual role of YAP in driving TGFβ-mediated endothelial-to-mesenchymal transition.Journal of cell science · 2021Article
- EGR1 and RXRA transcription factors link TGF-β pathway and CCL2 expression in triple negative breast cancer cells.Scientific reports · 2021Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Smad proteins transduce the transforming growth factor-beta (TGF-beta) signal at the cell surface into gene regulation in the nucleus. Upon TGF-beta treatment, the highly homologous Smad2 and Smad3 are phosphorylated by the TGF-beta receptor at the SSXS motif in the C-terminal tail. Here we show that in addition to the C-tail, three (S/T)-P sites in the Smad3 linker region, Ser(208), Ser(204), and Thr(179) are phosphorylated in response to TGF-beta. The linker phosphorylation peaks at 1 h after TGF-beta treatment, behind the peak of the C-tail phosphorylation. We provide evidence suggesting that the C-tail phosphorylation by the TGF-beta receptor is necessary for the TGF-beta-induced linker phosphorylation. Although the TGF-beta receptor is necessary for the linker phosphorylation, the receptor itself does not phosphorylate these sites. We further show that ERK is not responsible for TGF-beta-dependent phosphorylation of these three sites. We show that GSK3 accounts for TGF-beta-inducible Ser(204) phosphorylation. Flavopiridol, a pan-CDK inhibitor, abolishes TGF-beta-induced phosphorylation of Thr(179) and Ser(208), suggesting that the CDK family is responsible for phosphorylation of Thr(179) and Ser(208) in response to TGF-beta. Mutation of the linker phosphorylation sites to nonphosphorylatable residues increases the ability of Smad3 to activate a TGF-beta/Smad-target gene as well as the growth-inhibitory function of Smad3. Thus, these observations suggest that TGF-beta-induced phosphorylation of Smad3 linker sites inhibits its antiproliferative activity.
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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.