ArticleProceedings of the National Academy of Sciences of the United States of America2014
IκB kinase-induced interaction of TPL-2 kinase with 14-3-3 is essential for Toll-like receptor activation of ERK-1 and -2 MAP kinases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ.International journal of biological sciences · 2025Article
- IL-1β-activated PI3K/AKT and MEK/ERK pathways coordinately promote induction of partial epithelial-mesenchymal transition.Cell communication and signaling : CCS · 2024Article
- Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.Cell reports. Medicine · 2024Article
- ERK1/2 in immune signalling.Biochemical Society transactions · 2022Review
- TPL-2 Inhibits IFN-β Expression via an ERK1/2-TCF-FOS Axis in TLR4-Stimulated Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- OncogenicCancers · 2021Review
- The role of 14-3-3 proteins in cell signalling pathways and virus infection.Journal of cellular and molecular medicine · 2021Review
- Review
- TPL2 enforces RAS-induced inflammatory signaling and is activated by point mutations.The Journal of clinical investigation · 2020Article
- The IκB-protein BCL-3 controls Toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- ABIN2 Function Is Required To Suppress DSS-Induced Colitis by a Tpl2-Independent Mechanism.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.EMBO molecular medicine · 2018Article
- Recombinant protein ofOncotarget · 2017Article
- The Attenuation of 14-3-3ζ is Involved in the Caffeic Acid-Blocked Lipopolysaccharide-Stimulated Inflammatory Response in RAW264.7 Macrophages.Inflammation · 2017Article
- The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways.Cell death and differentiation · 2017Review
- Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3.The Biochemical journal · 2017Article
- An inflammatory bowel disease-risk variant in INAVA decreases pattern recognition receptor-induced outcomes.The Journal of clinical investigation · 2017Article
- Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- TLR and TNF-R1 activation of the MKK3/MKK6-p38α axis in macrophages is mediated by TPL-2 kinase.The Biochemical journal · 2016Article
- Penehyclidine ameliorates acute lung injury by inhibiting Toll-like receptor 2/4 expression and nuclear factor-κB activation.Experimental and therapeutic medicine · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The MEK-1/2 kinase TPL-2 is critical for Toll-like receptor activation of the ERK-1/2 MAP kinase pathway during inflammatory responses, but it can transform cells following C-terminal truncation. IκB kinase (IKK) complex phosphorylation of the TPL-2 C terminus regulates full-length TPL-2 activation of ERK-1/2 by a mechanism that has remained obscure. Here, we show that TPL-2 Ser-400 phosphorylation by IKK and TPL-2 Ser-443 autophosphorylation cooperated to trigger TPL-2 association with 14-3-3. Recruitment of 14-3-3 to the phosphorylated C terminus stimulated TPL-2 MEK-1 kinase activity, which was essential for TPL-2 activation of ERK-1/2. The binding of 14-3-3 to TPL-2 was also indispensible for lipopolysaccharide-induced production of tumor necrosis factor by macrophages, which is regulated by TPL-2 independently of ERK-1/2 activation. Our data identify a key step in the activation of TPL-2 signaling and provide a mechanistic insight into how C-terminal deletion triggers the oncogenic potential of TPL-2 by rendering its kinase activity independent of 14-3-3 binding.
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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.