Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resting natural killer (NK) cells express the p75 chain of the IL-2 receptor (IL-2R beta) and most NK cells express the CD2 (erythrocyte rosette) receptor. The cell adhesion molecule, LFA-3, is a natural co-ligand for CD2. Tac antigen (IL-2R alpha), a p55 IL-2R subunit, can be expressed after NK activation and may play a role in IL-2-induced NK proliferation. Little is known of the molecular mechanisms underlying cytokine production in NK cells. We investigated the roles of IL-2R alpha, IL-2R beta, and CD2/LFA-3 in the molecular regulation of NK cell granulocyte/macrophage-colony-stimulating factor (GM-CSF) production. Enriched populations of peripheral blood NK cells were separated into CD16-positive and CD16-negative fractions by flow cytometry; positively selected cells were greater than 97% positive for CD16 (the FcIII receptor for IgG which is present on almost all NK cells), less than 1% positive for the T cell antigen CD3, and did not demonstrate rearrangement of the T cell receptor beta chain gene by Southern blot. NK cell supernatants were harvested after 3-4 d of incubation with 0-100 U/ml IL-2, or after incubation with anti-CD2 (T11(3] MAb and sheep red blood cells (SRBC are a homologue for LFA-3). Parallel cell aliquots were harvested at 3-16 h for transcriptional run-on assays, S1 nuclease assays, and actinomycin D mRNA t1/2 determinations. IL-2-activated NK supernatants contained large amounts of GM-CSF (178 +/- 35 pg/ml) by ELISA as did supernatants from CD2-activated NK cells (T11(3) MAb + SRBC: 212 +/- 42) vs. less than 20 pg/ml for NK cells incubated alone or with either SRBC or T11(3) MAb alone. Sepharose-linked anti-CD3 MAb did not induce GM-CSF release from NK cells. By S1 analysis, both IL-2 and CD2 stimulation markedly augmented GM-CSF mRNA expression but with very different latencies of onset. IL-2R beta MAb inhibited greater than 85% of GM-CSF release from IL-2-activated NK cells and markedly suppressed IL-2-induced GM-CSF mRNA expression, whereas IL-2R alpha MAb even at 2,000-fold molar excess of IL-2 had little effect (less than 10%) on either GM-CSF release or mRNA expression. Run-on assays showed that GM-CSF is constitutively transcribed in NK cells and that IL-2 and CD2-activated cells had a three- to fourfold increased rate of GM-CSF transcription compared to nonstimulated cells. The t1/2 of GM-CSF mRNA in IL-2-activated NK cells was identical to that of unstimulated NK cells (15 min), whereas GM-CSF mRNA t1/2 in CD2-activated NK cells was increased 2.5-fold. We conclude that GM-CSF production in NK cells is regulated by both the IL-2Rbeta and the CD2 receptor but not by IL-2Ralpha, that both transcriptional and posttranscriptional signals act together to modulate the level of GM-CSF mRNA in NK cells, and that the molecular mechanisms underlying NK cell GM-CSF production are dependent in part on differential surface receptor activation.
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PMID:Production of granulocyte/macrophage-colony-stimulating factor by human natural killer cells. Modulation by the p75 subunit of the interleukin 2 receptor and by the CD2 receptor. 167 38

Interleukin 4 (IL 4), formerly known as B cell stimulatory factor 1 (BSF-1), has recently been described as a growth factor for T cells. The role of IL 4 in the putatively IL 2-independent growth of certain cloned T helper cells is unclear. D10.G4.1 (D10) is a conalbumin-specific helper T cell that has been employed extensively in the analysis of T cell activation and as an assay for the detection of IL 1. Previously, it was thought that IL 1 induced the expression of IL 2 receptors on D10 cells, thereby permitting D10 to proliferate in response to endogenously produced IL 2. However, we cannot detect IL 2 mRNA or protein in D10 cells or their supernatants as determined by the following criteria: monoclonal antibodies that neutralize the in vitro activity of murine IL 2 do not block the IL 1-dependent proliferation of D10 cells; no competitive binding for high-affinity IL 2 receptors with 125I-labeled IL 2 can be detected with medium conditioned by activated D10 cells; and Northern blot analysis and S1 nuclease protection assays, performed with cDNA probes for IL 2, do not detect mRNA for IL 2 under a variety of different activation conditions that foster autocrine growth of D10 cells. In contrast, activated D10 cells produce both IL 4 mRNA and protein as judged by similar criteria. Purified IL 4 has significant TCGF activity as measured by proliferation of HT-2 cells. This activity can be blocked completely by a monoclonal antibody to IL 4 (11B11). The proliferation of D10 cells in the presence of 3D3 (a clonotype-specific monoclonal anti-T cell receptor antibody) and IL 1 can be blocked completely by 11B11 antibody. Highly purified IL 4 alone cannot induce the proliferation of resting D10 cells; however, equivalent amounts of IL 4 in the presence of recombinant IL 1 induce significant D10 proliferation. Therefore, IL 1 appears to render D10 cells responsive to their autocrine growth signal. These data indicate that IL 4 serves as the autocrine T cell growth factor for D10 cells, and that exogenous IL 1 is required for the transduction of this growth signal. This may represent a more broadly applicable mechanism for the growth of certain subsets of T helper cells.
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PMID:Autocrine growth of T cells independent of interleukin 2: identification of interleukin 4 (IL 4, BSF-1) as an autocrine growth factor for a cloned antigen-specific helper T cell. 295 3

We cloned and compared the sequence of a rearranged human T cell receptor (TCR) V alpha J alpha gene and its germline counterparts. The only difference in the coding region sequence was confined to the joining region where three nucleotides, TTG, unaccountable by either V alpha or J alpha sequence, were present. By nuclease S1 mapping we identified the mRNA start of the alpha chain 70 nucleotides upstream from the initiator ATG. A 600 bp fragment containing the sequences upstream to the ATG drives the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene. This promoter activity is T cell specific since it can be demonstrated in human T cells but not in B cells or HeLa cells. A 1.1 kb BamHI- HindIII fragment located 5' to the first exon of the C alpha gene was found to enhance transcription from either the heterologous SV40 promoter or the homologous TCR alpha chain promoter. This enhancement activity was independent of the location of the fragment with respect to CAT and was specific to lymphoid cells (either T or B cells) but cannot be demonstrated in HeLa cells.
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PMID:Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor. 350 68