ArticleProceedings of the National Academy of Sciences of the United States of America2005
STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 80 citations in OpenAlex.
- The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.Journal of immunology research · 2026Review
- Understanding TAK1 deficiency in microglia: Dual mechanisms for photoreceptor protection in a mouse model of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Resolvin D1 Inhibits IL-6-Induced Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Targeting IL-6/STAT3 Signaling.Cell biochemistry and biophysics · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness.Scientific reports · 2023Article
- The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6.Molecular and cellular biochemistry · 2021Article
- Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies.International journal of molecular sciences · 2020Review
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.Pharmacological reviews · 2020Review
- Phospho-Ser727 triggers a multistep inactivation of STAT3 by rapid dissociation of pY705-SH2 through C-terminal tail modulation.International immunology · 2020Article
- TAK1/Map3k7 enhances differentiation of cardiogenic endoderm from mouse embryonic stem cells.Journal of molecular and cellular cardiology · 2019Article
- Leukocyte Immunoglobulin-Like Receptors A2 and A6 are Expressed in Avian Macrophages and Modulate Cytokine Production by Activating Multiple Signaling Pathways.International journal of molecular sciences · 2018Article
- Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines.International journal of molecular sciences · 2018Article
- STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle.PLoS pathogens · 2018Article
- NLK-mediated phosphorylation of HDAC1 negatively regulates Wnt signaling.Molecular biology of the cell · 2017Article
- Nemo-like kinase regulates the expression of vascular endothelial growth factor (VEGF) in alveolar epithelial cells.Scientific reports · 2016Article
- Multiple regulation pathways and pivotal biological functions of STAT3 in cancer.Scientific reports · 2015Review
- NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibition.Genes & development · 2015Article
- NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin.Journal of hematology & oncology · 2015Article
- Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.Molecular medicine reports · 2015Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transducer and activator of transcription 3 (STAT3) is activated by the IL-6 family of cytokines and growth factors. STAT3 requires phosphorylation on Ser-727, in addition to tyrosine phosphorylation on Tyr-705, to be transcriptionally active. In IL-6 signaling, the two major pathways that derive from the YXXQ and the YSTV motifs of gp130 cause Ser-727 phosphorylation. Here, we show that TGF-beta-activated kinase 1 (TAK1) interacts with STAT3, that the TAK1-Nemo-like kinase (NLK) pathway is efficiently activated by IL-6 through the YXXQ motif, and that this is the YXXQ-mediated H7-sensitive pathway that leads to STAT3 Ser-727 phosphorylation. Because NLK was recently shown to interact with STAT3, we explored the role of STAT3 in activating this pathway. Depletion of STAT3 diminished the IL-6-induced NLK activation by >80% without inhibiting IL-6-induced TAK1 activation or its nuclear entry. We found that STAT3 functioned as a scaffold for TAK1 and NLK in vivo through a region in its carboxyl terminus. Furthermore, the expression of the STAT3(534-770) region in the nuclei of STAT3-knockdown cells enhanced the IL-6-induced NLK activation in a dose-dependent manner but not the TGFbeta-induced NLK activation. TGFbeta did not cause STAT3 Ser-727 phosphorylation, even when the carboxyl region of STAT3 was expressed in the nuclei. Together, these results indicate that STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases, specifically in the YXXQ motif-derived pathway.
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