ArticleThe Journal of clinical investigation2004
A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 86 citations in OpenAlex.
- Toll-Like Receptor 2-Tpl2-Dependent ERK Signaling Drives Inverse Interleukin 12 Regulation in Dendritic Cells and Macrophages.Infection and immunity · 2020Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- Hypoxia potentiates monocyte-derived dendritic cells for release of tumor necrosis factor α via MAP3K8.Bioscience reports · 2018Article
- TPL2 Is a Key Regulator of Intestinal Inflammation in Clostridium difficile Infection.Infection and immunity · 2018Article
- Interleukin-33/ST2 axis promotes epithelial cell transformation and breast tumorigenesis via upregulation of COT activity.Oncogene · 2015Article
- Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma.Cancer immunology research · 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
- TPL2 mediates autoimmune inflammation through activation of the TAK1 axis of IL-17 signaling.The Journal of experimental medicine · 2014Article
- Tumor progression locus 2 (Tpl2) kinase promotes chemokine receptor expression and macrophage migration during acute inflammation.The Journal of biological chemistry · 2014Article
- Low intensity pulsed ultrasound (LIPUS) influences the multilineage differentiation of mesenchymal stem and progenitor cell lines through ROCK-Cot/Tpl2-MEK-ERK signaling pathway.The Journal of biological chemistry · 2014Article
- MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice.PloS one · 2014Article
- Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice.Journal of leukocyte biology · 2013Article
- TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Sterile inflammation in acetaminophen-induced liver injury is mediated by Cot/tpl2.The Journal of biological chemistry · 2013Article
- Immunomodulatory properties of subcellular fractions of a G+ bacterium, Bacillus firmus.Folia microbiologica · 2013Article
- Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012Article
- TEC and MAPK Kinase Signalling Pathways in T helper (TJournal of clinical & cellular immunology · 2012Article
- Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis.Oncogene · 2011Article
- Regulation and function of TPL-2, an IκB kinase-regulated MAP kinase kinase kinase.Cell research · 2011Review
- A multitude of kinases--which are the best targets in treating rheumatoid arthritis?Rheumatic diseases clinics of North America · 2010Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A serine/threonine protein kinase, Cot/Tpl2, is indispensable for extracellular signal-regulated kinase (ERK) activation and production of TNF-alpha and PGE2 in LPS-stimulated macrophages. We show here that Cot/Tpl2 is also activated by other Toll-like receptor (TLR) ligands. Bacterial DNA rich in the dinucleotide CG (CpG-DNA), unlike LPS or synthetic lipopeptide, activated ERK in a Cot/Tpl2-independent manner. Peritoneal macrophages and bone marrow-derived DCs from Cot/Tpl2-/- mice produced significantly more IL-12 in response to CpG-DNA than those from WT mice. Enhanced IL-12 production in Cot/Tpl2-/- macrophages is, at least partly, regulated at the transcriptional level, and the elevated IL-12 mRNA level in Cot/Tpl2-/- macrophages is accompanied by decreased amounts of IL-12 repressors, such as c-musculoaponeurotic fibrosarcoma (c-Maf) and GATA sequence in the IL-12 promoter-binding protein (GA-12-binding protein; GAP-12) in the nucleus. Consistently, Cot/Tpl2-/- mice showed Th1-skewed antigen-specific immune responses upon OVA immunization and Leishmania major infection in vivo. These results indicate that Cot/Tpl2 is an important negative regulator of Th1-type adaptive immunity, that it achieves this regulation by inhibiting IL-12 production from accessory cells, and that it might be a potential target molecule in CpG-DNA-guided vaccination.
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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.