ArticleMolecular and cellular biology2007
Phosphorylation of TPL-2 on serine 400 is essential for lipopolysaccharide activation of extracellular signal-regulated kinase in macrophages.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Free energy perturbation and machine learning-assisted identification of potential MAP3K8 hit molecules: a comprehensive structure- and ligand-based studies.Molecular diversity · 2026Article
- Article
- 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
- Tpl2 Ablation Leads to Hypercytokinemia and Excessive Cellular Infiltration to the Lungs During Late Stages of Influenza Infection.Frontiers in immunology · 2021Article
- Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes TPL2-Mediated Activation of the IRF3/IFN-β Signaling Pathway to Facilitate the Virus Replication.Frontiers in immunology · 2020Article
- Cimifugin Inhibits Inflammatory Responses of RAW264.7 Cells Induced by Lipopolysaccharide.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- ABIN2 Function Is Required To Suppress DSS-Induced Colitis by a Tpl2-Independent Mechanism.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas.Nature communications · 2015Article
- The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold.The Journal of biological chemistry · 2015Article
- 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
- Tumor progression locus 2-dependent oxidative burst drives phosphorylation of extracellular signal-regulated kinase during TLR3 and 9 signaling.The Journal of biological chemistry · 2014Article
- IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen.The Journal of experimental medicine · 2014Article
- 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.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- TNF and MAP kinase signalling pathways.Seminars in immunology · 2014Review
- Tumor progression locus 2 (Tpl2) kinase promotes chemokine receptor expression and macrophage migration during acute inflammation.The Journal of biological chemistry · 2014Article
- Mitogen-activated protein kinases in innate immunity.Nature reviews. Immunology · 2013Review
- Ebola virus VP35 induces high-level production of recombinant TPL-2-ABIN-2-NF-κB1 p105 complex in co-transfected HEK-293 cells.The Biochemical journal · 2013Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tumor progression locus 2 (TPL-2) kinase is essential for Toll-like receptor 4 activation of the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) and for upregulation of the inflammatory cytokine tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-stimulated macrophages. LPS activation of ERK requires TPL-2 release from associated NF-kappaB1 p105, which blocks TPL-2 access to its substrate, the ERK kinase MEK. Here we demonstrate that TPL-2 activity is also regulated independently of p105, since LPS stimulation was still needed for TPL-2-dependent activation of ERK in Nfkb1(-/-) macrophages. In wild-type macrophages, LPS induced the rapid phosphorylation of serine (S) 400 in the TPL-2 C-terminal tail. Mutation of this conserved residue to alanine (A) blocked the ability of retrovirally expressed TPL-2 to induce the activation of ERK in LPS-stimulated Nfkb1(-/-) macrophages. TPL-2(S400A) expression also failed to reconstitute LPS activation of ERK and induction of TNF in Map3k8(-/-) macrophages, which lack endogenous TPL-2. Consistently, the S400A mutation was found to block LPS stimulation of TPL-2 MEK kinase activity. Thus, induction of TPL-2 MEK kinase activity by LPS stimulation of macrophages requires TPL-2 phosphorylation on S400, in addition to its release from NF-kappaB1 p105. Oncogenic C-terminal truncations of TPL-2 that remove S400 could promote its transforming potential by eliminating this critical control step.
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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.