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

Interleukin-2 (IL-2), a crucial growth factor for mature T lymphocytes, is produced in fetal thymus under developmental control, although its biological significance remains unclear. We found that the two distinct subunits of the IL-2 receptor, i.e. the alpha-chain (IL-2R alpha) and the beta-chain (IL-2R beta), were expressed in an almost mutually exclusive fashion throughout fetal thymus ontogeny, and that the blockade of IL-2R beta, a signal transducing component of IL-2R, by administering a neutralizing mAb to IL-2R beta resulted in the complete and selective disappearance of Thy-1+ skin dendritic epidermal cells. Development of any other T cell subsets was uncompromised. This indicates that IL-2 plays a crucial role in the development of fetal V gamma 5+ cells and their descendants.
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PMID:In utero treatment with monoclonal antibody to IL-2 receptor beta-chain completely abrogates development of Thy-1+ dendritic epidermal cells. 135 Apr 62

Interleukin-2 (IL-2) potently stimulates natural killer (NK) cell proliferation and cytotoxic function. However, the molecular mechanisms by which IL-2 delivers activation signals from the IL-2 receptor to the NK cell interior are incompletely understood. Previous studies demonstrated that IL-2 stimulation induced the tyrosine phosphorylation of multiple proteins in NK cells, together with a prominent reduction in the electrophoretic mobility of p56lck. The present studies indicate that IL-2 induces a rapid (< or = 1 min) increase in the catalytic activity of p56lck, as measured by increases in protein tyrosine kinase activity in vitro. Furthermore, in response to IL-2, p56lck itself undergoes complex alterations in serine and tyrosine phosphorylation. Cyanogen bromide cleavage maps indicate that IL-2 stimulates a pronounced increase in the phosphorylation of the NH2-terminal region of p56lck containing multiple known sites of serine phosphorylation. In addition, IL-2 induced a marked increase in the phosphorylation of a COOH-terminal peptide containing the regulatory Tyr-505 residue of p56lck. These results suggest that p56lck serves as a substrate for both protein serine and tyrosine kinases activated during stimulation of this cell type with IL-2. Furthermore, these results indicate that the pleiotropic effects of IL-2 on NK cell physiology are initiated and regulated by a complex and multitiered interaction of different protein kinases including p56lck.
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PMID:Interleukin-2 signal transduction in human NK cells: multisite phosphorylation and activation of the tyrosine kinase p56lck. 138 59

We have developed a new technique for detecting binding of interleukin 2 (IL-2) to cells. This technique involves incubating the cells with IL-2 and then analysing the cell surface with specific anti-IL-2 antibodies and flow cytometry. This binding was only detected on tumor cells that possessed the p55 subunit of the IL-2 receptor. The role of p55 was ascertained by inhibition of the binding with a monoclonal antibody to p55. Although p55 is necessary for cytometrically detected IL-2 binding, further studies demonstrated that p55 is not sufficient. Thus, cytometrically-detected binding is likely to involved the contribution of other IL-2 surface receptors. Interleukin-2 binding to peripheral blood T lymphocytes and to a non-transformed T-cell clone was also detected cytometrically and it was shown that this binding is regulated by the activation status of the cells. Whereas IL-2 binding to quiescent T cells could not be detected, upon activation abundant binding was seen. The functional consequences of this type of cellular binding were studied. Interleukin-2 binding to cells during a short pulse was shown to have significant long-term consequences both for T-cell proliferation and for the enhancement of major histocompatibility complex (MHC)-non-restricted cytotoxicity.
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PMID:Cytometrically detected specific binding of interleukin 2 to cells. 149 54

Interleukin-2 (IL-2) and its receptor complex have become one of the most studied members of a growing family of protein hormones characterized by structural similarities in both ligands and their receptors. Structure-function studies of IL-2 have been complicated by the multimeric nature of its receptor. Two receptor subunits (55- and 75-kDa type I cell surface proteins) can participate to form the high affinity binding site. Although the IL-2 is apparently unique in some respects, similar subunit cooperativity has now been shown to be a common feature for other members of this receptor family. The availability of cell lines expressing the individual IL-2 receptor subunits has allowed detailed analysis of subunit binding characteristics. Results regarding the relationship of molecular recognition at each subunit to the mechanism of ligand binding at the high affinity site, however, have led to different interpretations. In this study we have employed previously prepared C-terminal IL-2 mutant proteins to examine receptor binding at all three classes using a variety of equilibrium and kinetic techniques. These results indicate that the high affinity IL-2 receptor complex includes the p55/p75 heterodimer prior to IL-2 binding and that both receptor subunits participate simultaneously in ligand capture.
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PMID:Recombinant interleukin-2 analogs. Dynamic probes for receptor structure. 152 87

Interleukin-2 (IL-2) plays a central role in the immune system by regulating the proliferation and differentiation of T lymphocytes. However, the molecular mechanism of the signal transduction through the IL-2 receptor is poorly understood. We have studied the role of phosphatidic acid (PA) on IL-2 signal transduction using cloned T lymphocytes. IL-2 stimulated a transient increase in the PA concentration in resting CTLL-2 cells prelabeled with [3H]palmitic acid. This effect was detected as early as 1 min after IL-2 addition and peaked at 5 min. IL-2 similarly increased phospholipase D activity in intact CTLL-2 cells, as inferred by phosphatidylethanol production. By contrast, IL-2 did not affect [3H]palmitic acid-labeled diacylglycerol levels. Furthermore, exogenous addition of several natural or synthetic PA to T cells mimicked IL-2 activity. Thus, PA were able to induce DNA synthesis on CTLL-2 cells, although this effect was only 10%-20% of that observed with IL-2. PA showed a synergistic effect with low doses of IL-2. In addition, PA was able to induce c-myc RNA transcription in CTLL-2 cells as well as IL-2 receptor (CD25) expression on the cell membrane with equal potency as saturating doses of IL-2. It is likely that IL-2-induced PA accumulation is a consequence of phospholipase D activation. This hypothesis is further supported by the fact that the addition of exogenous phospholipase D but not phosphatidylinositol-specific phospholipase C also reproduced the IL-2 or PA effects mentioned above. In summary, our results suggest a role of phospholipase D activation and PA formation as second messengers of IL-2 activity.
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PMID:Regulation of interleukin-2 responses by phosphatidic acid. 162 28

Interleukin-2 (IL-2) stimulates the proliferation of activated antigen-specific T cells through its interaction with high affinity receptors. This event is largely regulated by the inducible expression of the alpha-chain (CD25) which, in combination with the beta-chain and possibly additional chains, forms the high affinity IL-2 receptor (IL-2R) complex. From a concanavalin A (Con A)-activated ovine T-cell complementary DNA (cDNA) library we have isolated two cDNA clones which together constitute a 2650 base pair (bp) messenger RNA (mRNA) species encoding the ovine IL-2R alpha chain. The nucleotide sequence has high homology with analogous cDNA from other species and predicts a mature protein of 254 amino acids. In addition to the predominate 2.6 kilobase (kb) ovine IL-2R alpha chain mRNA species. Northern blot analysis of activated T-cell RNA revealed two larger mRNA species. The ovine IL-2R alpha chain cDNA was transfected into CHO cells and low affinity binding of human recombinant IL-2 demonstrated. Polyclonal antisera generated against the transfected cells cross-reacted with Con A-activated ovine lymphocytes. In addition these antisera were used to immunoprecipitate a unique 50,000 MW protein from the transfected cells. It is likely that this protein represents the expressed ovine IL-2R alpha chain cDNA which is heavily glycosylated as distinct from the 30,869 MW primary translation product. Southern blot analysis of ovine genomic DNA suggests that the ovine IL-2R alpha chain is encoded by a single copy gene.
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PMID:Molecular cloning, expression and characterization of the ovine IL-2R alpha chain. 162 87

Interleukin-2-dependent pathways of lymphocyte activation were investigated in canine peripheral blood lymphocytes (PBL) following stimulation with T-cell mitogens including phytohemagglutinin, phorbol ester (TPA), calcium ionophore (ionomycin), and human recombinant interleukin-2 (hrIL-2). The ability of the stimulated cells to produce interleukin-2 (IL-2) was determined using murine indicator cell lines. IL-2 receptor expression by mitogen-stimulated canine PBL was confirmed by the binding of hrIL-2 with high affinity, and with characteristics comparable to those of the human and murine IL-2 receptor. Examination of serum and PBL from two dogs that were treated with hrIL-2 and human recombinant tumor necrosis factor for systemic mast cell tumors showed that in one dog, IL-2 could be measured in the serum. Concurrently, the in vitro mitogenic response of this dog's PBL to hrIL-2 occurred earlier, possibly reflecting an increase in the relative number of IL-2-responsive cells within the PBL population.
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PMID:Immunophysiological studies of interleukin-2 and canine lymphocytes. 163 72

The phenotypic and functional nature of the lymphocytes that have been activated against autologous tumor cells and expanded in Interleukin-2 (IL-2) was studied in the context of their suitability for use in adoptive immunotherapy for cancer. While long-term co-cultures between autologous lymphocytes and tumor cells in the presence of exogenous IL-2 occasionally induced CD8+ cytolytic T cells, a substantial majority of such co-cultures generated predominantly CD4+ non-cytolytic or poorly cytolytic effector cells. In addition, these CD4+ non-cytolytic effector populations, and a number of CD4+ T cell clones derived from them, behaved like functional T suppressor (Ts) cells by elaborating a factor(s) that had profound negative effect(s) on activation of fresh T cells (inhibition of IL-2 synthesis, inhibition of IL-2 receptor [IL-2]-alpha expression, and inhibition of proliferation). Accordingly, infusion of these non-cytolytic populations capable of exhibiting such regulatory properties may have a substantial negative effect on host response toward cancer.
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PMID:Suppressor function of lymphocytes activated in in vitro co-culture against autologous tumor cells and expanded in interleukin-2. 168 55

Interleukin-2 (IL-2) was originally identified in 1976 as a growth factor for T lymphocytes. Since that time it has become an important mediator of immune function through its effects on the growth, development, and activity of T and B lymphocytes, natural killer cells, and lymphokine-activated killer cells. Only cells that bear a specific receptor for IL-2 respond to its immunoregulatory effects. Of all the lymphokine-receptor systems in immunology, perhaps most is known about the structure, function, and binding properties of IL-2 and its cognate receptor. There are two distinct, membrane-associated IL-2 binding components in the high-affinity IL-2 receptor: an alpha subunit and a beta subunit, which associate in a non-covalent manner. Each of these polypeptides can occur on the cell surface in the absence of the other and bind IL-2, although with only low or intermediate affinity relative to the high-affinity receptor complex. The primary structure of each chain has now been deduced from full-length cDNA. The rapid rate of association between IL-2 and the IL-2R alpha subunit is important in the formation of high-affinity binding sites, and the inducibility of the alpha gene contributes to the highly regulated and transient display of high-affinity IL-2R. The IL-2R beta chain controls the slow dissociation rate of IL-2 from the high-affinity receptor. Also, IL-2R beta appears centrally involved in internalization of IL-2 and signal transduction, functions mediated presumably through its long intracytoplasmic domain. However, the actual mechanism of signal transduction in the IL-2/IL-2R system remains undefined. IL-2R beta is a member of a novel family of cytokine-receptor proteins that includes receptors for IL-4, IL-6, and erythropoietin.
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PMID:Interleukin-2 and the IL-2 receptor: new insights into structure and function. 169 45

Interleukin-2 (IL-2) stimulates proliferation of T lymphocytes and is involved in the activation of both natural killer and lymphokine-activated killer precursor cells. The intracellular messengers which mediate IL-2-dependent events have not yet been identified. IL-2 receptor is not a protein-tyrosine kinase. Activation of a cellular protein-tyrosine kinase and direct association of a protein-tyrosine kinase activity with the IL-2 receptor occurs within minutes of IL-2 stimulation. We investigated the activation of phosphatidylinositol 3-kinase (PI 3-kinase) in IL-2-mediated signal transduction using the IL-2-dependent murine T-cell line, CTLL-2, and human phytohemagglutinin-stimulated peripheral blood lymphocytes (phytohemagglutinin blasts). Within a minute following stimulation of these cells with IL-2, PI 3-kinase activity could be detected in antiphosphotyrosine (anti-P-Tyr) antibody immunoprecipitates. IL-2 triggered a direct association of PI 3-kinase with the IL-2 receptor as detected in immunoprecipitates using anti-IL-2 receptor beta chain antibody. In vivo labeled CTLL-2 cells have a time-dependent increase in D-3-phosphorylated polyphosphoinositides following stimulation with IL-2. This is the first group of second messengers identified in IL-2-mediated signal transduction.
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PMID:Interleukin-2 receptor regulates activation of phosphatidylinositol 3-kinase. 171 78


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