ArticleThe Journal of biological chemistry2009
A negative feedback control of transforming growth factor-beta signaling by glycogen synthase kinase 3-mediated Smad3 linker phosphorylation at Ser-204.
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 52 papers.
What it found
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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.
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Who cites it
52 citing papers in PubMed, 76 citations in OpenAlex.
- Porphyromonas gingivalis Type 9 Secretion System Promotes Dysregulation of Vascular Smooth Muscle Cell Plasticity With Perturbed TGF-β/Smad Signaling.MicrobiologyOpen · 2025Article
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- 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
- Application of dental pulp stem cells for bone regeneration.Frontiers in medicine · 2024Review
- Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma.Frontiers in oncology · 2024Review
- Targeting transforming growth factor beta signaling in metastatic osteosarcoma.Journal of bone oncology · 2023Review
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- The Effect of CHIR 99021, a Glycogen Synthase Kinase-3β Inhibitor, on Transforming Growth Factor β-Induced Tenon Fibrosis.Investigative ophthalmology & visual science · 2021Article
- Osteoarthritis-Related Inflammation Blocks TGF-β's Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region.International journal of molecular sciences · 2021Article
- MicroRNA-99b-3p promotes angiotensin II-induced cardiac fibrosis in mice by targeting GSK-3β.Acta pharmacologica Sinica · 2021Article
- Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value.Medical sciences (Basel, Switzerland) · 2021Review
- How scars shape the neural landscape: Key molecular mediators of TGF-β1's anti-neuritogenic effects.PloS one · 2020Article
- Review
- Phosphorylation status at Smad3 linker region modulates transforming growth factor-β-induced epithelial-mesenchymal transition and cancer progression.Cancer science · 2019Review
- Clinico-Pathological Importance of TGF-β/Phospho-Smad Signaling during Human Hepatic Fibrocarcinogenesis.Cancers · 2018Review
- [Tumor necrosis factor-α and transforming growth factor-βNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- MEKK1, JNK, and SMAD3 mediate CXCL12-stimulated connective tissue growth factor expression in human lung fibroblasts.Journal of biomedical science · 2018Article
- Regulation of Hematopoiesis and Hematological Disease by TGF-β Family Signaling Molecules.Cold Spring Harbor perspectives in biology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Through the action of its membrane-bound type I receptor, transforming growth factor-beta (TGF-beta) elicits a wide range of cellular responses that regulate cell proliferation, differentiation, and apo ptosis. Many of these signaling responses are mediated by Smad proteins. As such, controlling Smad activity is crucial for proper signaling by TGF-beta and its related factors. Here, we show that TGF-beta induces phosphorylation at three sites in the Smad3 linker region in addition to the two C-terminal residues, and glycogen synthase kinase 3 is responsible for phosphorylation at one of these sites, namely Ser-204. Alanine substitution at Ser-204 and/or the neighboring Ser-208, the priming site for glycogen synthase kinase 3 in vivo activity, strengthened the affinity of Smad3 to CREB-binding protein, suggesting that linker phosphorylation may be part of a negative feedback loop that modulates Smad3 transcriptional activity. Thus, our findings reveal a novel aspect of the Smad3 signaling mechanism that controls the final amplitude of cellular responses to TGF-beta.
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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.