ArticleProceedings of the National Academy of Sciences of the United States of America2008
Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet.Genome research · 2025Article
- TPL2 kinase activity is required forFrontiers in immunology · 2025Article
- The Influenza-Induced Pulmonary Inflammatory Exudate in Susceptible Tpl2-Deficient Mice Is Dictated by Type I IFN Signaling.Inflammation · 2023Article
- Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity.PloS one · 2022Article
- Biological Landscape of Triple Negative Breast Cancers Expressing CTLA-4.Frontiers in oncology · 2020Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.Cell reports · 2019Article
- Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer.Oncogenesis · 2019Article
- Identification of the transgenic integration site in 2C T cell receptor transgenic mice.Transgenic research · 2018Article
- Tumor Progression Locus 2 (Tpl2) Activates the Mammalian Target of Rapamycin (mTOR) Pathway, Inhibits Forkhead Box P3 (FoxP3) Expression, and Limits Regulatory T Cell (Treg) Immunosuppressive Functions.The Journal of biological chemistry · 2016Article
- NF-κB1 p105 suppresses lung tumorigenesis through the Tpl2 kinase but independently of its NF-κB function.Oncogene · 2016Article
- In vivo gene manipulation reveals the impact of stress-responsive MAPK pathways on tumor progression.Cancer science · 2015Review
- 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
- Article
- Genetic and pharmacologic inhibition of Tpl2 kinase is protective in a mouse model of ventilator-induced lung injury.Intensive care medicine experimental · 2014Article
- Pharmacological inhibition of TPL2/MAP3K8 blocks human cytotoxic T lymphocyte effector functions.PloS one · 2014Article
- Tpl2 knockout keratinocytes have increased biomarkers for invasion and metastasis.Carcinogenesis · 2013Article
- TPL2 kinase is a suppressor of lung carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Altered prostanoid signaling contributes to increased skin tumorigenesis in Tpl2 knockout mice.PloS one · 2013Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The protein kinase encoded by the Tpl2 protooncogene plays an obligatory role in the transduction of Toll-like receptor and death receptor signals in macrophages, B cells, mouse embryo fibroblasts, and epithelial cells in culture and promotes inflammatory responses in animals. To address its role in T cell activation, we crossed the T cell receptor (TCR) transgene 2C, which recognizes class I MHC presented peptides, into the Tpl2(-/-) genetic background. Surprisingly, the TCR2C(tg/tg)/Tpl2(-/-) mice developed T cell lymphomas with a latency of 4-6 months. The tumor cells were consistently TCR2C(+)CD8(+)CD4(-), suggesting that they were derived either from chronically stimulated mature T cells or from immature single positive (ISP) cells. Further studies showed that the population of CD8(+) ISP cells was not expanded in the thymus of TCR2C(tg/tg)/Tpl2(-/-) mice, making the latter hypothesis unlikely. Mature peripheral T cells of Tpl2(-/-) mice were defective in ERK activation and exhibited enhanced proliferation after TCR stimulation. The same cells were defective in the induction of CTLA4, a negative regulator of the T cell response, which is induced by TCR signals via ERK. These findings suggest that Tpl2 functions normally in a feedback loop that switches off the T cell response to TCR stimulation. As a result, Tpl2, a potent oncogene, functions as a tumor suppressor gene in chronically stimulated T cells.
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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.