ArticleProceedings of the National Academy of Sciences of the United States of America2005
Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- IP-LC-MS/MS-Based Identification of Candidate TPL2 (MAP3K8)-Associated Proteins in Porcine PK-15 Cells.Journal of mass spectrometry : JMS · 2026Article
- TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ.International journal of biological sciences · 2025Article
- Zinc in Human Health and Infectious Diseases.Biomolecules · 2022Review
- Cell adhesion tunes inflammatory TPL2 kinase signal transduction.Cellular and molecular life sciences : CMLS · 2022Article
- IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2 activation in tumor cells.EXCLI journal · 2022Article
- OncogenicCancers · 2021Review
- Foot-and-Mouth Disease Virus Structural Protein VP1 Destroys the Stability of TPL2 Trimer by Degradation TPL2 to Evade Host Antiviral Immunity.Journal of virology · 2021Article
- 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
- Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia.Molecular oncology · 2018Article
- Zinc as a Gatekeeper of Immune Function.Nutrients · 2017Review
- Zinc Signals and Immunity.International journal of molecular sciences · 2017Review
- Classifying kinase conformations using a machine learning approach.BMC bioinformatics · 2017Article
- KinView: a visual comparative sequence analysis tool for integrated kinome research.Molecular bioSystems · 2016Article
- AGut · 2016Article
- The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold.The Journal of biological chemistry · 2015Article
- Article
- Tumor progression locus 2 (Tpl2) kinase as a novel therapeutic target for cancer: double-sided effects of Tpl2 on cancer.International journal of molecular sciences · 2015Review
- The interplay between cyclic AMP, MAPK, and NF-κB pathways in response to proinflammatory signals in microglia.BioMed research international · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The serine-threonine protein kinase encoded by the Tpl2 protooncogene transduces Toll-like and death receptor signals in a variety of cell types and plays an important role in innate immunity and inflammation. Differential translational initiation of the Tpl2 mRNA gives rise to 58-kDa (p58) and 52-kDa (p52) isoforms. In unstimulated cells, both isoforms are stabilized and inactivated by stoichiometric binding to NF-kappaB1/p105. After lipopolysaccharide or TNF-alpha stimulation, p58 is released from p105 preferentially relative to p52. The released p58 is active but unstable and undergoes rapid degradation via the proteasome. Recent studies revealed that Tpl2 undergoes phosphorylation at Thr-290 and that phosphorylation at this site is required for activation. Here, we present evidence showing that it is the p58 isoform that is preferentially phosphorylated at Thr-290 and that phosphorylation is more efficient when p58 is complexed to p52. Because p58 is preferentially released from p105 after stimulation, we examined whether Tpl2 phosphorylation at this site controls the dissociation of the two proteins in response to external signals and the subsequent events leading to the activation of Tpl2. The results showed that lipopolysaccharide-induced Tpl2 phosphorylation at Thr-290 in macrophages promotes the release of Tpl2 from p105, contributes to the enzymatic activation of the Tpl2 kinase, and is required for the degradation of Tpl2 via the proteasome.
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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.