共查询到20条相似文献,搜索用时 15 毫秒
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Rauen T Benedyk K Juang YT Kerkhoff C Kyttaris VC Roth J Tsokos GC Tenbrock K 《The Journal of biological chemistry》2011,286(37):32366-32372
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Juang YT Rauen T Wang Y Ichinose K Benedyk K Tenbrock K Tsokos GC 《The Journal of biological chemistry》2011,286(3):1795-1801
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Transformation of T lymphocytes by the v-fos oncogene 总被引:4,自引:0,他引:4
V E Valge-Archer J de Villiers A J Sinskey A Rao 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(12):4355-4364
Activation of T lymphocytes through the T cell antigen receptor has been shown to stimulate a rapid and transient accumulation of c-fos mRNA and protein. Transfection of a normal murine T lymphocyte clone with the FBJ-v-fos oncogene resulted in generation of a cell line that was morphologically transformed, had lost the requirement for IL-2 for proliferation, and was tumorigenic in adult syngeneic mice; however, the transformed cells retained the ability to proliferate in response to IL-2. The transformed cells did not show constitutive expression of IL-2 or c-fos mRNA, although the promoter regions of both IL-2 and c-fos genes contain AP-1 sites that are expected to be targets for binding of Fos/Jun complexes. In contrast, the transformed T cells showed increased constitutive expression of IL-2R alpha and c-myc mRNA; these genes may represent cellular targets for transformation by v-fos and physiologic activation by c-fos. We discuss the possibility that these transformed cells behave as cells partially activated through the TCR, and that transformation occurs through a mechanism independent of IL-2. 相似文献
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Rauen T Hedrich CM Juang YT Tenbrock K Tsokos GC 《The Journal of biological chemistry》2011,286(50):43437-43446
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Analysis of the AP-1 sites in the IL-2 promoter. 总被引:18,自引:0,他引:18
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Regulation of IL-10 gene expression in Th2 cells by Jun proteins 总被引:5,自引:0,他引:5
Wang ZY Sato H Kusam S Sehra S Toney LM Dent AL 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(4):2098-2105
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Vaishali R. Moulton Andrew R. Gillooly George C. Tsokos 《The Journal of biological chemistry》2014,289(7):4126-4134
T cells from patients with systemic lupus erythematosus (SLE) exhibit reduced expression of the critical T cell receptor (TCR)-associated CD3ζ signaling chain and are poor producers of the vital cytokine IL-2. By oligonucleotide pulldown and mass spectrometry discovery approaches, we identified the splicing regulator serine/arginine-rich splicing factor (SRSF) 1 or splicing factor 2/alternative splicing factor (SF2/ASF) to be important in the expression of CD3ζ chain. Importantly, increases in the expression of SRSF1 rescued IL-2 production in T cells from patients with SLE. In this study, we investigated the regulation of SRSF1 expression in resting and activated human T cells. We found that T cell stimulation induced a rapid and significant increase in mRNA expression of SRSF1; however, protein expression levels did not correlate with this increase. Co-engagement of CD28 induced a similar mRNA induction and reduction in protein levels. Proteasomal but not lysosomal degradation was involved in this down-regulation as evidenced by blocking with specific inhibitors MG132 and bafilomycin, respectively. Immunoprecipitation studies showed increased ubiquitination of SRSF1 in activated T cells. Interestingly, T cells from patients with SLE showed increased ubiquitination of SRSF1 when compared with those from healthy individuals. Our results demonstrate a novel mechanism of regulation of the splicing factor SRSF1 in human T cells and a potential molecular mechanism that controls its expression in SLE. 相似文献