PubMed:18287049 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":642,"end":658},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":693,"end":698},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":1502,"end":1507},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0015760"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0005070"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0005070"}],"text":"Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells.\nThe 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."}

{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"T2","span":{"begin":127,"end":404},"obj":"Sentence"},{"id":"T3","span":{"begin":405,"end":585},"obj":"Sentence"},{"id":"T4","span":{"begin":586,"end":688},"obj":"Sentence"},{"id":"T5","span":{"begin":689,"end":874},"obj":"Sentence"},{"id":"T6","span":{"begin":875,"end":1039},"obj":"Sentence"},{"id":"T7","span":{"begin":1040,"end":1176},"obj":"Sentence"},{"id":"T8","span":{"begin":1177,"end":1319},"obj":"Sentence"},{"id":"T9","span":{"begin":1320,"end":1448},"obj":"Sentence"},{"id":"T10","span":{"begin":1449,"end":1558},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"T2","span":{"begin":127,"end":404},"obj":"Sentence"},{"id":"T3","span":{"begin":405,"end":585},"obj":"Sentence"},{"id":"T4","span":{"begin":586,"end":688},"obj":"Sentence"},{"id":"T5","span":{"begin":689,"end":874},"obj":"Sentence"},{"id":"T6","span":{"begin":875,"end":1039},"obj":"Sentence"},{"id":"T7","span":{"begin":1040,"end":1176},"obj":"Sentence"},{"id":"T8","span":{"begin":1177,"end":1319},"obj":"Sentence"},{"id":"T9","span":{"begin":1320,"end":1448},"obj":"Sentence"},{"id":"T10","span":{"begin":1449,"end":1558},"obj":"Sentence"}],"text":"Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells.\nThe 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."}