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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous paper [Horuk, Huang, Covington & Newton (1987) J. Biol. Chem. 262, 16275-16278] we reported that there were fundamental differences in the biochemical properties of the interleukin-1 (IL-1) receptor between Raji and EL4 cell lines. In the present study we have investigated the basis for these differences. Kinetic studies measuring the on and off rates of IL-1 receptor binding revealed that the low-affinity IL-1-binding sites observed in Raji cells, compared with EL4 cells, result from a combination of a lower association rate and a higher dissociation rate in the Raji cells. The turnover of the Raji IL-1 receptor, measured by inhibiting protein synthesis with cycloheximide, was much faster than that of the EL4 IL-1 receptor, with a half-time of 2 h as against 5 h. Treatment of 125I-IL-1-labelled IL-1 receptors in Raji and EL4 cells with neuraminidase decreased their molecular mass by approx. 2-5 kDa as assessed by SDS/polyacrylamide-gel electrophoresis (PAGE). The covalently labelled IL-1 receptors in both cell types were sensitive to treatment with endoglycosidase F, which decreased their molecular mass on SDS/PAGE by 12-13 kDa. Incubation of Raji cells with maximally stimulating doses of IL-1 resulted in an increase in the nascent RNA levels of several genes, including the IL-2 receptor and the proto-oncogenes c-Ha-ras and c-myc.
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PMID:The interleukin-1 receptor in Raji human B-lymphoma cells. Molecular characterization and evidence for receptor-mediated activation of gene expression. 252 95

Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.
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PMID:Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. 254 May 28

The interleukin 2-diphtheria toxin-related fusion protein (IL-2-toxin) rapidly inhibits protein synthesis in IL-2 receptor (IL-2R)-bearing phytohemagglutinin-activated T cells but transiently stimulates DNA synthesis. At 7 hr after interaction with IL-2R+ phytohemagglutinin-activated T cells, IL-2-toxin-treated cells bear augmented steady-state levels of c-myc, interferon gamma, and IL-2R mRNA; these effects are indistinguishable from those produced by recombinant IL-2. Amplification of IL-2 sequences by the polymerase chain reaction reveals an increased level of IL-2 mRNA in cell cultures treated with recombinant IL-2, IL-2-toxin, and cycloheximide. These results suggest that IL-2-toxin can affect de novo IL-2 gene transcription/mRNA stabilization through independent mechanisms exerted by both the IL-2R binding domain and ADP-ribosyltransferase activity of the fusion protein. After 20 hr of culture, IL-2R mRNA was markedly decreased in both IL-2-toxin- and cycloheximide-treated phytohemagglutinin-activated T cells. Although interaction of IL-2-toxin with IL-2R+ T cells initially mimics the stimulatory effects of IL-2 upon c-myc, interferon gamma, IL-2R, and IL-2 gene expression, the consequences of inhibition of protein synthesis mediated by the ADP-ribosyltransferase activity of the toxin dominate after 7 hr and are indistinguishable from those effects mediated by cycloheximide.
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PMID:Sequential effects of interleukin 2-diphtheria toxin fusion protein on T-cell activation. 259 81

We have provided evidence that tumor necrosis factor alpha (TNF-alpha) enhances the proliferation and the state of activation of human thymocytes cultured with concanavalin A or interleukin 2 (IL-2), as evidenced by an increase in the expression of the c-myc gene and the gene of the IL-2 receptor (alpha-chain, Tac antigen) and by the expression of Tac antigen on the cell surface. Our observations suggest that TNF-alpha interacts with IL-2 and with another factor(s) which is induced in the course of activation by concanavalin A, since the immunosuppressant drug cyclosporin A-, which inhibits thymocyte activation, prevents the effect of TNF-alpha on thymocytes activated with concanavalin A, whereas anti-Tac, which prevents the binding of IL-2 to its receptor without affecting the production of IL-2 or the expression of IL-2-specific mRNA, inhibits proliferation only partially. By contrast, anti-Tac inhibits the response to TNF-alpha of thymocytes induced with IL-2 completely. These observations show that TNF-alpha exerts a potentially important immunoregulatory effect in synergy with IL-2 on thymocytes, which could contribute to tumor rejection. In addition, we show that activated human thymocytes express the TNF-alpha gene and that the expression of this gene is inhibited by cyclosporin A and dexamethasone.
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PMID:Immunoregulation and production of tumor necrosis factor alpha by human thymocytes. 265 63

The effects of 1,25(OH)2D3 and dexamethasone on cellular proliferation and gene expression of the HTLV-I-infected T-cell line, KH-2, established from a patient with adult T-cell leukemia, endemic in the south-west Japanese islands and the Caribbean, were examined. KH-2 cells are integrated by HTLV-I proviral DNA and expressed mRNA for c-myc, IL-2 receptor alpha-chain (IL-2R alpha), and T-cell receptor beta-chain (TCR beta) while it did not express IL-2 mRNA. 1,25(OH)2D3 and dexamethasone did not suppress the mRNA levels of HTLV-I, IL-2R alpha or TCR beta but reduced the c-myc mRNA level. The reduction of c-myc mRNA level was marked in 1,25(OH)2D3-treated cells but relatively weak in dexamethasone-treated cells. This inhibitory effect of the steroid hormones correlated with the inhibition of KH-2 cell proliferation.
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PMID:Suppression of c-myc mRNA expression by steroid hormones in HTLV-I-infected T-cell line, KH-2. 279 41

The relationship between induction of nuclear proto-oncogenes and cellular proliferation is not fully understood. To better define this relationship, we have studied c-fos, c-myc, and c-myb mRNA induction in T lymphocytes where early and late activation events have been clearly delineated. In T cells, initial activation from G0 to G1 results from stimulation of either the antigen/major histocompatibility complex receptor (T3-Ti) or the T11 structure; further cycle progression and proliferation follow interaction of interleukin 2 (IL-2) with the IL-2 receptor. These events can be dissected with monoclonal antibodies to T3 or T11 which cause early activation but differ in their ability to initiate IL-2-dependent cycle progression and proliferation. In T lymphocytes triggered through either T3-Ti or T11, c-fos is induced with a nonmitogenic activation signal whereas c-myb is only induced with a mitogenic signal capable of triggering IL-2 and IL-2 receptor expression. Furthermore, c-myc induction is biphasic and associated with both early and late activation events. Early c-myc, like c-fos, is induced with a nonmitogenic signal. In contrast, induction of late c-myc, like that of c-myb, requires a mitogenic signal. Thus, appearance of c-fos and initial c-myc mRNA seem to be early responses to membrane signaling whereas late c-myc and c-myb are more directly associated with actual cellular proliferation. That nonmitogenic stimulation of T cells via T3-Ti not only abrogates T11-mediated proliferation but also eliminates late c-myc and c-myb transcription further supports this notion.
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PMID:Differential expression of nuclear proto-oncogenes in T cells triggered with mitogenic and nonmitogenic T3 and T11 activation signals. 282 Nov 8

We demonstrate that purified interleukin 2 (IL-2) can directly upregulate IL-2 receptor expression on phytohemagglutinin-activated T lymphocytes maintained in culture until IL-2 receptor expression had markedly declined. The IL-2-induced increase in IL-2 receptor number is maximal within 12 hr, requires new RNA and protein synthesis, and is mediated by an interaction of ligand with the high-affinity receptors for IL-2. IL-2 stimulation results in increased accumulation of IL-2 receptor mRNA within 4 hr, while an increase in IL-2 receptor gene transcription is detected within 30 min in isolated nuclei. In addition, IL-2 incubation results in increased amounts of c-myc and transferrin receptor mRNA, but it does not augment levels of mRNA encoding the beta chain of the T-cell receptor for antigen. These results demonstrate that IL-2 can directly upregulate transcription and expression of its own receptor and, therefore, indicate that IL-2 may regulate IL-2-dependent immune responses, in part, by influencing the expression of IL-2 receptors.
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PMID:Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene. 298 68

Nuclear transcription assays were performed with isolated nuclei from human peripheral blood T lymphocytes stimulated with phytohemagglutinin and phorbol myristate acetate to determine the kinetics of transcriptional activity of various genes occurring in T cell activation. Although silent in resting T cells, the genes encoding c-myc and the interleukin 2 (IL-2) receptor were induced early, preceding gamma interferon (IFN-gamma), IL-2, and transferrin receptor gene transcription. Transcriptional activity of these genes fell after their respective peaks, indicating that the expression of these genes is a transient event during T cell activation. With the exception of the transferrin receptor gene, the kinetics of induction of these genes were not altered by concentrations of cycloheximide that inhibited protein synthesis. These data indicate that the induction of genes encoding c-myc, IL-2, IL-2 receptor, and IFN-gamma occur independently of the sequential production of the proteins they encode.
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PMID:Sequential expression of genes involved in human T lymphocyte growth and differentiation. 298 8

Elevation of intracellular cyclic adenosine 3':5' monophosphate (cAMP) inhibits interleukin 2 (IL-2)-stimulated proliferation of a murine cytotoxic cell clone, CT6. The effects of antiproliferative dosages of stable cAMP-derivative, 8-bromoadenosine 3':5'-monophosphate (8-Br-cAMP), on steady state mRNA expression stimulated by IL-2 was examined. IL-2 stimulated mRNA accumulation of three nuclear proto-oncogenes c-fos, c-myc, and c-myb. 8-Br-cAMP alone stimulated c-fos, c-myb, and IL-2 receptor mRNA accumulation as determined by Northern blot analysis. 8-Br-cAMP, however, markedly inhibited c-myc expression stimulated by IL-2. Furthermore, although c-fos and IL-2 receptor mRNA expression was potentiated by 8-Br-cAMP, suppression of protein synthesis was seen. We show that antiproliferative cAMP stimulates similar mRNA expression as does IL-2, with the exception of c-myc. Although a comparative stimulation of steady state mRNA accumulation of some genes occurs, cAMP may profoundly effect protein synthesis. cAMP, therefore, acts on multiple targets involved in the macromolecular events stimulated by IL-2.
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PMID:Effects of anti-proliferative cyclic AMP on interleukin 2-stimulated gene expression. 304 Aug 63

Three Hodgkin's disease-derived cell lines were analysed for the organization of immunoglobulin and T cell receptor genes, for the expression of the interleukin 2 (IL-2) receptor gene, and for the cellular oncogene c-myc. All three cell lines have characteristic genotypic markers of lymphoid cells and can be classified as immature lymphoid cells with respect to the incomplete expression of their antigen receptor genes. This immature genotype is in contrast to the expression of activation antigens Ki-1 (CD 30), IL-2 receptor (CD 25), and HLA-DR. The results obtained are in agreement with studies obtained from primary Hodgkin's lymphomas, which are activated by as yet unknown mechanisms.
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PMID:Molecular analysis of Hodgkin's disease-derived cell lines. 313 69


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