UNIPROT:P14784 - FACTA Search

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

Soluble proteins of the human immunodeficiency virus (HIV) might play a significant role in the pathogenesis of HIV infection. The addition of synthetic Tat peptides, but not that of the recombinant Nef or Vif protein, inhibited proliferative responses of CD4+ tetanus antigen-specific, exogenous interleukin-2 (IL-2)-independent T-cell clones in a dose-dependent manner. In addition, Tat peptides inhibited the anti-CD3 monoclonal antibody-induced proliferative responses of both purified CD4+ and CD8+ T cells. Tat did not affect proliferative responses induced by phorbol myristate acetate plus ionomycin. The Tat peptides at the concentrations used (0.1 to 3 micrograms/ml) did not affect the viability of the cells as determined by trypan blue exclusion. Treatment of Tat peptides with polyclonal Tat antibodies abrogated the inhibitory effect of Tat. Soluble Tat proteins secreted by HeLa cells transfected with the tat gene also inhibited antigen-induced proliferation of the T-cell clones. Tat inhibited the anti-CD3 monoclonal antibody-induced IL-2 mRNA expression and IL-2 secretion but did not affect IL-2 receptor alpha-chain mRNA or protein expression on peripheral blood T cells. Finally, treatment of T-cell clones with the Tat peptide did not affect the antigen-induced increase in intracellular calcium, hydrolysis of phosphatidyl inositol to inositol trisphosphate, or translocation of protein kinase C from the cytosol to the membrane. These studies demonstrate that the mechanism of the Tat-mediated inhibition of T-cell functions involves a phospholipase C gamma 1-independent pathway.
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PMID:Human immunodeficiency virus Tat induces functional unresponsiveness in T cells. 798 46

CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.
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PMID:CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. 810 64

Blood proteases regulate cellular growth through the recognition and signaling properties of specialized membrane receptors. Previous studies have identified a novel lymphocyte activation-dependent antigen, denominated effector cell protease receptor-1 (EPR-1), which binds the coagulation protease factor Xa on various leukocyte subsets. Here we show that occupancy of EPR-1 with physiologic concentrations of factor Xa (15-75 nM), or with "surrogate" monoclonal antibody ligands, stimulates proliferation of both T and B lymphocyte subsets and augments CD3-dependent lymphocyte proliferation. At suboptimal responder cell concentrations, ligation of EPR-1 costimulates lymphocyte proliferation in the presence of accessory signals, i.e., phorbol ester, IL-2. At higher responder cell concentrations, occupancy of EPR-1 per se is sufficient to initiate lymphocyte proliferation. EPR-1-dependent T cell activation is associated with early surface expression of IL-2 receptor on target cells, thus increasing by five- to eightfold their mitogenic responsiveness to very low doses of IL-2 (0.2 U/ml). Consistent with a postulated role in transmembrane signal transduction, cross-linking of EPR-1 transiently increases cytosolic free [Ca2+]i in single adherent T cells. These findings suggest that proteases ubiquitously generated in vivo might contribute a regulatory mechanism of cytokine- or antigen receptor-dependent T cell activation and identify EPR-1 as a novel signal-transducing molecule of lymphocyte stimulation.
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PMID:Protease-dependent T cell activation: ligation of effector cell protease receptor-1 (EPR-1) stimulates lymphocyte proliferation. 818 Oct 72

Previous studies established that low in vitro temperatures (27 degrees C, termed nonpermissive) suppressed murine primary thymus-dependent (TD), but not primary thymus-independent (TI) or secondary TD, antibody responses. Suppression was rescued by the addition of oleic acid (18:1), recombinant interleukin (rIL)-2 and/or rIL-4, but not rIL-1. These observations suggested that low temperatures suppress the functions of virgin T cells (Tv) but not those of memory T cells (Tm), B cells, or accessory cells and that hypothetically 18:1 may rescue suppressed responses by altering the membranes of Tv cells, allowing them to proliferate and subsequently secrete interleukins. In this study negatively selected Tm and Tv cells were stimulated with various mitogens at 37 or 27 degrees C. The results indicated that proliferation was suppressed at 27 degrees C to all mitogens tested. The subsequent addition of 18:1 induced proliferative responses at 27 degrees C to both concanavalin A (Con A) and a combination of 12-O-tetradecanoylphorbol 13-acetate (TPA) and calcium ionophore (A23187), but not to phytohemagglutinin-P (PHA). Both Tm and Tv cells showed significant secretion of IL-2 and expression of IL-2 receptor (IL-2R) at 27 degrees C in response to all mitogens, irrespective of proliferation, and the subsequent addition of 18:1 caused little or no change in the levels of IL-2 secretion or IL-2R expression. These findings indicate that suppression of Tm and Tv cell proliferative responses occurs irrespective of IL-2R expression and, unlike antibody production, of IL-2 secretion. Furthermore, it appears that 18:1 can synergistically act with Con A or TPA/A23187, but not PHA, in activating Tm and Tv cells to induce proliferation at 27 degrees C. These findings suggest differences in signal transduction mechanisms between these various mitogens.
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PMID:The effects of temperature and oleic acid on murine memory and virgin T cell activation: interleukin-2 secretion and interleukin-2 receptor expression. 824 70

The T cell antigen receptor (TCR) and the interleukin-2 receptor (IL-2R) are important receptors in haematopoiesis since they control the activation and growth of T lymphocytes, respectively. The term T cell activation refers to the events that occur as T cells progress from the G0 to the G1 phase of the cell cycle and is characterised by the production of a wide range of cytokines and other immunomodulators crucial for the growth and development of other haematopoietic cells. Activation also induces the T cells to express on their cell surface high affinity receptors for various cytokines which enable the T cell to respond to the different cytokines generated during an immune response. One well characterised event that occurs when mature T cells are activated is the production of the cytokine IL-2 and the acquisition by the T cell of high affinity IL-2 receptors. Interaction between IL-2 and its cellular receptor than direct T cell growth. One notable difference between TCR and IL-2R signal transduction is that the TCR regulates intracellular calcium and stimulates protein kinase C whereas the IL-2 receptor does not. The present review focuses on TCR and IL-2R regulation of two common intracellular signalling pathways: the regulation of a PtdIns-3-kinase and the activation of the guanine nucleotide binding proteins p21ras. The aim is to illustrate differences in the mechanisms that couple the TCR and IL-2R to these two signalling pathways and attempt to explain the apparent discrepancy of TCR and IL-2R regulation of shared signal transduction pathways even though these receptors mediate quite distinct biological responses.
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PMID:Regulation of PtdIns-3-kinase and the guanine nucleotide binding proteins p21ras during signal transduction by the T cell antigen receptor and the interleukin-2 receptor. 826 Jun 48

Ca2+/calmodulin-dependent protein kinases are implicated in regulating the Ca2+ signaling involved in T cell activation and in thymocyte selection. One of the earliest events in signaling through the T cell antigen receptor is activation of the protein tyrosine kinase p56lck. Following T cell activation or signaling through the IL-2 receptor, Ca(2+)-mediated phosphorylation of p56lck occurs on serine/threonine residues. Isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinases, CaM kinase-II and CaM kinase-Gr are found in human T lymphocytes. CaM kinase-II, but not CaM kinase-Gr, phosphorylates the T cell tyrosine kinase p56lck in vitro. Tryptic phosphopeptide maps indicate that CaM kinase-II phosphorylates p56lck on multiple sites in vitro. Kinase assays of p56lck modified by CaM kinase-II indicate that CaM kinase-II modification does not appreciably affect p56lck phosphotransfer activity.
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PMID:p56lck phosphorylation by Ca2+/calmodulin-dependent protein kinase type II. 829 50

The goal of this investigation was to determine if human natural killer (NK) cells were susceptible to the cytolytic effects of the Actinobacillus actinomycetemcomitans leukotoxin (LTX). Following treatment with LTX (0-200 ng/ml), NK cell activation by interleukin-2 (IL-2) was evaluated. LTX inhibited the IL-2-induced expression of both CD69 and the IL-2 receptor. Furthermore, the up-regulation of CD56 was also impaired. To determine whether the observed functional deficits were the result of cell death, NK cell viability was evaluated by flow cytometry. Changes in forward and side light scatter patterns consistent with cell death were observed within 60 min. Direct analysis of cell viability by measuring propidium iodide exclusion, however, indicated little change in the viability of LTX-treated NK cells. Electron microscopic analysis of NK cells exposed to LTX revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation, and condensation of nucleoplasm. However, no change in membrane integrity was initially noted. Finally, LTX caused a rapid and sustained elevation in the intracellular levels of Ca2+. These morphological and biochemical changes are consistent with the notion of programmed cell death.
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PMID:Flow cytometric analysis of the cytotoxic effects of Actinobacillus actinomycetemcomitans leukotoxin on human natural killer cells. 830 Dec 11

We investigated activation of mitogen-activated protein (MAP) kinase, also known as microtubule associated protein-2 kinase (MAP-2K), by recombinant interleukin-2 (rIL-2) in phytohaemagglutinin (PHA)-induced peripheral blood lymphoblasts (PBL). MAP-kinase activation has been implicated in growth of lymphocytes and other cell types. Enzyme activity was purified from cell lysates by ion-exchange chromatography and activity measured by the ability to phosphorylate the substrates MAP-2 and myelin basic protein peptide (APRTPGGRR) in vitro. Recombinant IL-2 stimulated a variable (two-to 10-fold) and evanescent MAP-2K response which was dose dependent over the range 0-50 U/ml. In contrast to MAP-kinase activation by the CD3 receptor, activation by the IL-2 receptor (IL-2R) proceeded independently from protein kinase C (PKC) and extracellular-free Ca2+. MAP-kinase activation by CD3 involves an activation cascade which depends on Ca2+ influx and PKC activation. These events culminate in tyrosine phosphorylation and activation of MAP kinase. Recombinant IL-2 induced tyrosine phosphorylation of several intracellular proteins, including a 40,000 MW substrate which co-electrophoresed with ERK-2 on SDS-PAGE. The ERK-2 gene encodes a 41,000 MW MAP-2K and is subject to regulation by a variety of mitogens and growth factors in lymphocytes and non-lymphoid cells. MAP-kinase activation by rIL-2 was abrogated when PHA blasts were pretreated with the tyrosine protein kinase (TPK) inhibitor, methyl-2,5-dihydroxy-cinnamate. Although the TPK, p56lck, has been implicated in the activation of MAP kinase and the function of IL-2R, we found no mobility shift from a 56,000 to a 60,000 MW position as seen during PKC activation. Together these data suggest that tyrosine phosphorylation is critical to IL-2-mediated signal transduction and that MAP kinase is one of the cellular intermediates involved in this pathway.
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PMID:Activation of mitogen-activated protein kinase/ERK-2 in phytohaemagglutin in blasts by recombinant interleukin-2: contrasting features with CD3 activation. 838 29

The alloreactive cytotoxic T lymphocytes (CTL) were generated by coculturing peripheral blood mononuclear cells (PBMC) with allogeneic Sa cells (an Epstein-Barr virus [EBV]-transformed B-cell line). The CTL did not proliferate in response to UV-B-irradiated Sa cells unless exogenous interleukin-2 (IL-2) was present, although they could kill the UV-B-irradiated Sa cells. The results indicate that UV-B-irradiated Sa cells do not provide sufficient signals for the proliferation of the CTL while they can be recognized by CTL and induce high-affinity IL-2 receptor (IL-2R) expression on them. The alloreactive CTL could be rendered anergic by previous exposure to UV-B-irradiated Sa cells. The alloreactive CTL previously stimulated with UV-B-irradiated Sa cells failed to proliferate in response to nontreated Sa cells. Proliferation of the anergic CTL could not be restored by Sa cells and exogenous IL-2 but by the combination of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). The anergic CTL showed a considerably low cytotoxic activity against Sa target cells. The expression of TCR on the anergic CTL was downregulated while expression of high-affinity IL-2R was upregulated. Their CD28 and CD8 expression were unchanged. In addition, the proliferative response and cytotoxicity of the anergic CTL to Sa cells could be restored after the cells had been rested for 7 days to allow reexpression of TCR. These results suggest that downregulation of T-cell receptor (TCR) and impairment in the post-IL-2/IL-2R signaling pathway are relevant to the clonal anergy induced in the alloreactive CTL by stimulation of UV-B-irradiated Sa cells.
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PMID:UV irradiation can induce in vitro clonal anergy in alloreactive cytotoxic T lymphocytes. 839 72

The effects mediated by a combined stimulation of cAMP- and protein kinase C (PKC)-dependent pathways have been investigated in different cellular systems, and it has been shown that they may complement each other in activating cell proliferation and differentiation. In this report, we show that upon the stimulation of both pathways T lymphocytes became refractory to activation via the CD3/T cell receptor (TcR) complex. T cells preincubated with phorbol 12-myristate 13-acetate (PMA) and dibutyryl cAMP (Bt2cAMP) displayed a deficient proliferative ability in response to anti-CD3 mAb stimulation, whereas lymphocytes treated individually with either Bt2cAMP or PMA responded comparably to untreated samples. We detected an association between the reduced mitogenic response and low expression of both interleukin-2 (IL-2) and the alpha chain (CD25) of the IL-2 receptor (IL-2R). Analysis of intracellular Ca2+ mobilization suggested that the CD3/TcR-dependent signal transduction was impaired in PMA/Bt2cAMP-treated cells. Remarkably, we observed that these samples displayed a persistent expression of the c-fos protooncogene, associated to an increased AP-1 DNA-binding activity, whereas no variations of CREB or NF-kB were detected. Neither Bt2cAMP nor PMA individually mediated these sustained effects, which therefore appear as a consequence of the interplay between both metabolic stimuli. Altogether, the data provide the evidence that both pathways complement each other in regulating gene expression and, conversely, downregulate the TcR transduction mechanisms.
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PMID:Costimulation of cAMP and protein kinase C pathways inhibits the CD3-dependent T cell activation and leads to a persistent expression of the AP-1 transcription factor. 839 37

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