| http://purl.uniprot.org/citations/23874982 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23874982 | http://www.w3.org/2000/01/rdf-schema#comment | "4-1BB (CD137), an inducible costimulatory molecule, strongly enhances the proliferation and effector function of CD8(+) T cells. Since the serine/threonine kinase, glycogen synthase kinase-3 (GSK-3), is involved in a variety of signaling pathways of cellular proliferation, migration, immune responses, and apoptosis, we examined whether 4-1BB signaling activates GSK-3/β-catenin signaling and downstream transcription factors to enhance the proliferation of CD8(+) T cells. 4-1BB signaling induces rapid activation of ERK and IκB degradation, and shows delayed activation of AKT at 24 h post 4-1BB stimulation on anti-CD3 activated T cells. ERK and AKT signals were required for sustained β-catenin levels by inactivating GSK-3, which was also observed with delayed kinetics after 4-1BB stimulation. As a transcriptional partner of β-catenin, 4-1BB signaling decreased levels of FOXO1 and increased levels of stimulatory TCF1 in CD8(+) T cells at 2-3 days but not at early time points after 4-1BB engagement. The enhanced proliferation of CD8(+) T cells due to 4-1BB signaling was completely abolished by treatment with the TCF1/β-catenin inhibitor quercetin. These results show that 4-1BB signaling enhances the proliferation of activated CD8(+) T cells by activating the TCF1/β-catenin axis via the PI3K/AKT/ERK pathway. As effects of 4-1BB on AKT, FOXO1, β-catenin and GSK-3β showed delayed kinetics it is likely that an intervening molecule induced by 4-1BB and ERK signaling in activated T cells is responsible for these effects. These effects were observed on CD8(+) but not on CD4(+) T cells. Moreover, 4-1BB appeared to be unique among several TNFRs tested in inducing increase in stimulatory over inhibitory TCF-1."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0069677"xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Kim Y.H."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Kim C.H."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Lee S.J."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Lee D.G."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Lee D.Y."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Choi B.K."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/author | "Kwon B.S."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/pages | "e69677"xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/title | "4-1BB signaling activates the t cell factor 1 effector/beta-catenin pathway with delayed kinetics via ERK signaling and delayed PI3K/AKT activation to promote the proliferation of CD8+ T Cells."xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/23874982 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23874982 |
| http://purl.uniprot.org/citations/23874982 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23874982 |
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| http://purl.uniprot.org/uniprot/#_Q3UZT7-mappedCitation-23874982 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23874982 |
| http://purl.uniprot.org/uniprot/#_Q99LY6-mappedCitation-23874982 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23874982 |
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| http://purl.uniprot.org/uniprot/#_P70304-mappedCitation-23874982 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23874982 |