ArticleMolecular and cellular biology2003
NF-kappaB1 p105 negatively regulates TPL-2 MEK kinase activity.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 123 citations in OpenAlex.
- A Phosphoproteomic Analysis of Mycobacterial PknG-Mediated Host Immune Evasion.Journal of proteome research · 2025Article
- TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ.International journal of biological sciences · 2025Article
- Dynamical and combinatorial coding by MAPK p38 and NFκB in the inflammatory response of macrophages.Molecular systems biology · 2024Article
- Article
- A Dual Role for Cysteinyl Leukotriene Receptors in the Pathogenesis of Corneal Infection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Biochemically deleterious human NFKB1 variants underlie an autosomal dominant form of common variable immunodeficiency.The Journal of experimental medicine · 2021Article
- OncogenicCancers · 2021Review
- TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells.Cellular & molecular immunology · 2021Article
- TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria.The EMBO journal · 2021Article
- Kinase inhibition in autoimmunity and inflammation.Nature reviews. Drug discovery · 2021Review
- Review
- 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
- Involvement of Alveolar Macrophages and Neutrophils in Acute Lung Injury After Scorpion Envenomation: New Pharmacological Targets.Inflammation · 2018Article
- Assaying kinase activity of the TPL-2/NF-κB1 p105/ABIN-2 complex using an optimal peptide substrate.The Biochemical journal · 2018Article
- NF-κB p65 and p105 implicate in interleukin 1β-mediated COX-2 expression in melanoma cells.PloS one · 2018Article
- Tumor Necrosis Factor Receptor-Associated Factor Regulation of Nuclear Factor κB and Mitogen-Activated Protein Kinase Pathways.Frontiers in immunology · 2018Review
- TLR and TNF-R1 activation of the MKK3/MKK6-p38α axis in macrophages is mediated by TPL-2 kinase.The Biochemical journal · 2016Article
- NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells.The Journal of experimental medicine · 2016Article
- Ubiquitin signaling in immune responses.Cell research · 2016Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the oncogenic potential of the MEK kinase TPL-2 (Cot) requires deletion of its C terminus. This mutation also weakens the interaction of TPL-2 with NF-kappaB1 p105 in vitro, although it is unclear whether this is important for the activation of TPL-2 oncogenicity. It is demonstrated here that TPL-2 stability in vivo relies on its high-affinity, stoichiometric association with NF-kappaB1 p105. Formation of this complex occurs as a result of two distinct interactions. The TPL-2 C terminus binds to a region encompassing residues 497 to 534 of p105, whereas the TPL-2 kinase domain interacts with the p105 death domain. Binding to the p105 death domain inhibits TPL-2 MEK kinase activity in vitro, and this inhibition is significantly augmented by concomitant interaction of the TPL-2 C terminus with p105. In cotransfected cells, both interactions are required for inhibition of TPL-2 MEK kinase activity and, consequently, the catalytic activity of a C-terminally truncated oncogenic mutant of TPL-2 is not affected by p105. Thus, in addition to its role as a precursor for p50 and cytoplasmic inhibitor of NF-kappaB, p105 is a negative regulator of TPL-2. Insensitivity of C-terminally truncated TPL-2 to this regulatory mechanism is likely to contribute to its ability to transform cells.
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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.