Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have delineated a positive regulatory element in the interleukin-2 receptor alpha-chain gene (IL-2R alpha) between positions -299 and -243 that can potently activate a heterologous (herpesvirus thymidine kinase [tk]) promoter in phorbol myristate acetate (PMA)-induced Jurkat T cells and is functional when cloned in either orientation. This enhancerlike element contains a site (-268/-257) that can bind NF-kappa B; however, unlike the immunoglobulin kappa gene kappa B enhancer element, the IL-2R alpha kappa B-like site alone can only weakly activate a heterologous promoter. Adjacent 5' and 3' sequences also weakly activate the tk-CAT vector, but constructs combining the IL-2R alpha kappa B-like site plus adjacent 5' and 3' sequences potently activate gene expression. This combination of regions is essential for potent PMA-induced transcription from the tk promoter. Experiments using constructs in which IL-2R alpha upstream sequences are sequentially deleted suggested that there is a region 5' of position -299 which can suppress IL-2R alpha promoter and/or enhancer activity. Thus, it is possible that both positive and negative elements may be important in the regulation of IL-2R alpha gene transcription.
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PMID:Delineation of an enhancerlike positive regulatory element in the interleukin-2 receptor alpha-chain gene. 215 27

Human peripheral blood monocytes (Mo) constitutively display the beta-chain of the receptor for IL-2, whereas expression of the IL-2R alpha-chain is not constitutive but inducible with IL-2. Here we report that binding of human IL-2 to its binding site leads to transcriptional activation of the macrophage CSF (M-CSF) gene in Mo resulting in accumulation of M-CSF mRNA and subsequent release of bioactive M-CSF protein as demonstrated by ELISA and inhibition of IL-2 induced release of an activity-stimulating growth of monocyte-type colonies by a neutralizing anti-M-CSF antibody. Transcriptional activation of the M-CSF gene by IL-2 is preceded by enhanced binding activity of the transcription factor NF-kappa B to its recognition sequence in the 5' regulatory enhancer region of the M-CSF gene. Moreover, using a heterologous promoter (herpes thymidine kinase) construct containing the NF-kappa B consensus sequence, it is shown that NF-kappa B binding by an IL-2-induced monocyte-derived nuclear protein confers reporter gene (human growth hormone) activity. Taken together, our findings indicate that IL-2 induces gene expression of M-CSF in human blood-derived Mo and provide evidence for involvement of NF-kappa B in transcriptional regulation of this gene.
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PMID:Transcriptional activation of the macrophage colony-stimulating factor gene by IL-2 is associated with secretion of bioactive macrophage colony-stimulating factor protein by monocytes and involves activation of the transcription factor NF-kappa B. 851 75

Soluble interleukin-2 receptor-alpha (IL-2Ralpha) has been reported to be increased in the sera of patients with advanced tuberculosis, and levels decline after therapy in accordance with improvement of radiologic findings. We investigated expression of the IL-2Ralpha in bronchoalveolar lavage (BAL) cells in active pulmonary tuberculosis, and evaluated the mechanism Mycobacterium tuberculosis induces in the IL-2Ralpha using the THP-1 mononuclear phagocyte cell line. We found IL-2Ralpha expression to be increased in BAL cells from involved sites of active pulmonary tuberculosis. Expression of the alpha-chain of IL-2Ralpha on peripheral blood monocytes (PBM) was induced by M. tuberculosis by flow cytometry evaluation. Northern analysis demonstrated increased IL-2Ralpha gene expression after stimulation with M. tuberculosis which was further induced by interferon-gamma (IFN-gamma). The IL-2Ralpha promoter containing the nuclear factor kappa B (NF-kappaB) site was transcriptionally induced by M. tuberculosis and this NF-kappaB site could confer inducibility to a heterologous herpes thymidine kinase (TK) promoter by M. tuberculosis. Electrophoretic mobility shift assays (EMSAs) revealed specific binding of nuclear protein to the NF-kappaB site upon induction with M. tuberculosis. Using antibodies against the p50 and p65 subunits of NF-kappaB in EMSAs, the involvement of both p50 and p65 proteins was further demonstrated. Functional expression of the IL-2Ralpha on mononuclear phagocytes in M. tuberculosis infection may play an important immunomodulatory role in the host response.
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PMID:Activation of NF-kappaB in Mycobacterium tuberculosis- induced interleukin-2 receptor expression in mononuclear phagocytes. 1019 84