ArticleThe Journal of biological chemistry
The phosphorylation of the Smad2/3 linker region by nemo-like kinase regulates TGF-β signaling.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Ubiquitination-Related Diagnostic Biomarkers for Diabetic Nephropathy: Insights From Multiomic Analysis, Drug Docking, and Experimental Validation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Microbial Monotherapy With Leuconostoc sp LB-P8 Improves Inflammation and Fibrosis in Mouse Primary Sclerosing Cholangitis by Inhibiting Transforming Growth Factor β1/SMAD Signaling.Cellular and molecular gastroenterology and hepatology · 2026Article
- Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.Frontiers in immunology · 2026Review
- Proliferative Effect of Proanthocyanidins on HGF-1 and HPDLF Cells: An In Vitro Study.Medicina (Kaunas, Lithuania) · 2025Article
- A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SMAD2 S-palmitoylation promotes its linker region phosphorylation and TScience signaling · 2025Article
- M2 macrophage-derived exosomes reverse TGF-β1-induced epithelial mesenchymal transformation in BEAS-2B cells via the TGF-βRI/Smad2/3 signaling pathway.European journal of medical research · 2025Article
- The Role of Twisted Gastrulation 1 (TWSG1) Gene in TGF-β Signaling Linked to Cancer: A Comprehensive Review.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- Downregulation of SMAD2 and SMAD4 is associated with poor prognosis and shorter survival in esophageal squamous cell carcinoma.Molecular biology reports · 2025Article
- Interrelation of Natural Polyphenol and Fibrosis in Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2024Review
- Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.International journal of molecular sciences · 2024Article
- Protein phosphatase 6 promotes transforming growth factor-β signaling in mouse embryonic fibroblasts.The Journal of veterinary medical science · 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
- MircroRNA-92b as a negative regulator of the TGF-β signaling by targeting the type I receptor.iScience · 2023Article
- Article
- Prospective use of amniotic mesenchymal stem cell metabolite products for tissue regeneration.Journal of biological engineering · 2023Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Smad2 and Smad3 (Smad2/3) are structurally similar proteins that primarily mediate the transforming growth factor-β (TGF-β) signaling responsible for driving cell proliferation, differentiation, and migration. The dynamics of the Smad2/3 phosphorylation provide the key mechanism for regulating the TGF-β signaling pathway, but the details surrounding this phosphorylation remain unclear. Here, using in vitro kinase assay coupled with mass spectrometry, we identified for the first time that nemo-like kinase (NLK) regulates TGF-β signaling via modulation of Smad2/3 phosphorylation in the linker region. TGF-β-mediated transcriptional and cellular responses are suppressed by NLK overexpression, whereas NLK depletion exerts opposite effects. Specifically, we discovered that NLK associates with Smad3 and phosphorylates the designated serine residues located in the linker region of Smad2 and Smad3, which inhibits phosphorylation at the C terminus, thereby decreasing the duration of TGF-β signaling. Overall, this work demonstrates that phosphorylation on the linker region of Smad2/3 by NLK counteracts the canonical phosphorylation in response to TGF-β signals, thus providing new insight into the mechanisms governing TGF-β signaling transduction.
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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.