Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of Stat5 by many cytokines implies that it cannot alone insure the specificity of the regulation of its target genes. We have evidenced a physical and functional interaction between members of two unrelated transcription factor families, Ets-1, Ets-2 and Stat5, which could contribute to the proliferative response to interleukin 2. Competition with GAS- and EBS-specific oligonucleotides and immunoassays with a set of anti-Stat and anti-Ets families revealed that the IL-2-induced Stat5-Ets complex recognizes several GAS motifs identified as target sites for activated Stat5 dimers. Coimmunoprecipitation experiments evidenced that a Stat5/Ets-1/2 complex is formed in vivo in absence of DNA. GST-pull down experiments demonstrated that the C-terminal domain of Ets-1 is sufficient for this interaction in vitro. Cotransfection experiments in Kit225 T cells resulted in cooperative transcriptional activity between both transcription factors in response to a combination of IL-2, PMA and ionomycin. A Stat5-Ets protein complex was the major inducible DNA-binding complex bound to the human IL-2rE GASd/EBSd motif in long-term proliferating normal human T cells activated by CD2 and CD28. These results suggest that the inducible Stat5-Ets protein interaction plays a role in the regulation of gene expression in response to IL-2 in human T lymphocytes.
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PMID:IL-2 and long-term T cell activation induce physical and functional interaction between STAT5 and ETS transcription factors in human T cells. 1081

CD94 is a C-type lectin required for the dimerization of the CD94/NKG2 family of receptors, which are expressed on NK cells and T cell subsets. Little is known about CD94 gene expression and the elements that regulate CD94 transcription. In this study, we report that CD94 gene expression is regulated by distal and proximal promoters that transcribe unique initial exons specific to each promoter. This results in two species of transcripts; the previously described CD94 mRNA and a novel CD94C mRNA. All NK cells and CD94(+), CD8(+) alphabeta T cells transcribe CD94 mRNA. Stimulation of NK and CD8(+) alphabeta T cells with IL-2 or IL-15 induced the transcription of CD94C mRNA. The distal and proximal promoters both contain elements with IFN-gamma-activated and Ets binding sites, known as GAS/EBS. Additionally, an unknown element, termed site A, was identified in the proximal promoter. EMSA analyses showed that constitutive factors could bind to oligonucleotide probes containing each element. After treatment of primary NK cells with IL-2 or IL-15, separate inducible complexes could be detected with oligonucleotide probes containing either the proximal or distal GAS/EBS elements. These elements are highly conserved between mice and humans, which suggests that both species regulate CD94 gene expression via mechanisms that predate their evolutionary divergence.
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PMID:Human CD94 gene expression: dual promoters differing in responsiveness to IL-2 or IL-15. 1460 29