ArticleMolecular and cellular biology2014
S6K1 negatively regulates TAK1 activity in the toll-like receptor signaling pathway.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Effects of miR-128-3p on Renal Inflammation in a Rat Periodontitis Model.Dentistry journal · 2025Article
- The Role of S6K1 in Aging and Alzheimer's Disease: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Knowledge mapping of links between dendritic cells and allergic diseases: A bibliometric analysis (2004-2023).Heliyon · 2024Article
- HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer.Cell death & disease · 2022Article
- Beyond controlling cell size: functional analyses of S6K in tumorigenesis.Cell death & disease · 2022Review
- Poly(I:C) preconditioning protects the heart against myocardial ischemia/reperfusion injury through TLR3/PI3K/Akt-dependent pathway.Signal transduction and targeted therapy · 2020Article
- Transcriptional analysis of THP-1 cells infected with Leishmania infantum indicates no activation of the inflammasome platform.PLoS neglected tropical diseases · 2020Article
- Direct imaging of the recruitment and phosphorylation of S6K1 in the mTORC1 pathway in living cells.Scientific reports · 2019Article
- TAK1 mediates convergence of cellular signals for death and survival.Apoptosis : an international journal on programmed cell death · 2019Review
- Inhibition of p70 S6 kinase activity by A77 1726 induces autophagy and enhances the degradation of superoxide dismutase 1 (SOD1) protein aggregates.Cell death & disease · 2018Article
- The metabolic regulator mTORC1 controls terminal myeloid differentiation.Science immunology · 2017Article
- Article
- Peroxiredoxin-6 Negatively Regulates Bactericidal Activity and NF-κB Activity by Interrupting TRAF6-ECSIT Complex.Frontiers in cellular and infection microbiology · 2017Article
- Peroxiredoxin-3 Is Involved in Bactericidal Activity through the Regulation of Mitochondrial Reactive Oxygen Species.Immune network · 2016Article
- TIPE2 (Tumor Necrosis Factor α-induced Protein 8-like 2) Is a Novel Negative Regulator of TAK1 Signal.The Journal of biological chemistry · 2016Article
- High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs.The Journal of nutrition · 2016Article
- Cereblon negatively regulates TLR4 signaling through the attenuation of ubiquitination of TRAF6.Cell death & disease · 2016Article
- GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis.Genes and immunity · 2016Article
- Charged MVB protein 5 is involved in T-cell receptor signaling.Experimental & molecular medicine · 2016Article
- Toll-like receptor 2 and type 2 diabetes.Cellular & molecular biology letters · 2016Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor β (TGF-β)-activated kinase 1 (TAK1) is a key regulator in the signals transduced by proinflammatory cytokines and Toll-like receptors (TLRs). The regulatory mechanism of TAK1 in response to various tissue types and stimuli remains incompletely understood. Here, we show that ribosomal S6 kinase 1 (S6K1) negatively regulates TLR-mediated signals by inhibiting TAK1 activity. S6K1 overexpression causes a marked reduction in NF-κB and AP-1 activity induced by stimulation of TLR2 or TLR4. In contrast, S6K1(-/-) and S6K1 knockdown cells display enhanced production of inflammatory cytokines. Moreover, S6K1(-/-) mice exhibit decreased survival in response to challenge with lipopolysaccharide (LPS). We found that S6K1 inhibits TAK1 kinase activity by interfering with the interaction between TAK1 and TAB1, which is a key regulator protein for TAK1 catalytic function. Upon stimulation with TLR ligands, S6K1 deficiency causes a marked increase in TAK1 kinase activity that in turn induces a substantial enhancement of NF-κB-dependent gene expression, indicating that S6K1 is negatively involved in the TLR signaling pathway by the inhibition of TAK1 activity. Our findings contribute to understanding the molecular pathogenesis of the impaired immune responses seen in type 2 diabetes, where S6K1 plays a key role both in driving insulin resistance and modulating TLR signaling.
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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.