ArticleThe EMBO journal2018
The IKK-related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 96 citations in OpenAlex.
- Oncogenic EGFR rewires STING-TBK1 signalosomes to license DNA damage tolerance in NSCLC.The EMBO journal · 2026Article
- Targeting the GSK-3β/mTOR axis: a novel pharmacological strategy for preeclampsia prevention and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Selective degradation of TBK1 uncovers mechanistic insights into blocking ccRCC progression.Cell chemical biology · 2026Article
- Targeting integrin αVβ3-Ptgs2-mTOR signaling rescues bone formation in osteoporosis: from molecular mechanism toward therapy.Cellular & molecular biology letters · 2026Article
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Article
- Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.Autophagy · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- AXL-TBK1 driven AKT3 activation promotes metastasis.Science signaling · 2024Article
- Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications.World journal of diabetes · 2024Review
- Mechanism of TBK1 activation in cancer cells.Cell insight · 2024Review
- Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.The EMBO journal · 2024Article
- Article
- Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.EMBO molecular medicine · 2024Review
- Activation of protein kinase receptor (PKR) plays a pro-viral role in mammarenavirus-infected cells.Journal of virology · 2024Article
- Ex vivo treatment with poly (I:C) alleviates the exhausted phenotype of tumor-infiltrating TCD8Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- The interplay between autophagy and cGAS-STING signaling and its implications for cancer.Frontiers in immunology · 2024Review
- Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases.Journal of molecular and cellular cardiology · 2024Review
- The Role of cGAS-STING Signalling in Metabolic Diseases: from Signalling Networks to Targeted Intervention.International journal of biological sciences · 2024Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i.e., TLR3; TLR4), revealing a stimulus-selective role for TBK1 in mTORC1 regulation. By studying cultured macrophages and those isolated from genome edited mTOR S2159A knock-in mice, we show that mTOR S2159 phosphorylation promotes mTORC1 signaling, IRF3 nuclear translocation, and IFN-β production. These data demonstrate a direct mechanistic link between TBK1 and mTORC1 function as well as physiologic significance of the TBK1-mTORC1 axis in control of innate immune function. These data unveil TBK1 as a direct mTORC1 activator and suggest unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity, tumorigenesis, and disorders linked to chronic inflammation.
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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.