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

The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains, the last of which is also used in the receptors for IL-4, IL-7, IL-9, IL-13, and IL-15. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2R beta and IL-2R gamma, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here we summarize our current understanding of the mechanisms by which IL-2R transmit signals by using multiple protein kinases. In fact, at least four protein tyrosine kinases (PTKs) are physically associated with IL-2R: p56lck (and its members), Syk PTK, and the Janus kinases, Jak1 and Jak3. cDNA expression studies revealed that the activation of these PTKs is critical for IL-2-induced proliferative signal transmission. Our findings indicate that a unique property of the IL-2R cytoplasmic domains is to recruit a variety of signaling molecules, which may suggest a mechanism by which these PTKs and other signaling molecules function in concert.
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PMID:IL-2 signaling involves recruitment and activation of multiple protein tyrosine kinases by the IL-2 receptor. 748 66

It has previously been described that V gamma 3 cells can proliferate extensively in vitro in the presence of different cytokines. Here, the role of cytokines in the maintenance of V gamma 3 cells in the thymus has been determined. Culture of fetal thymocytes in cell suspension for 24 h showed that, whereas immature TCRlowHSAhigh V gamma 3 cells remained viable, all mature TCRhighHSAlow V gamma 3 cells died. These cells died by apoptosis since protein synthesis was required and flow cytometric analysis as well as DNA gel electrophoresis showed that the DNA was degraded to oligonucleosomal bands. Addition of IL-2, IL-4 or IL-7 to suspension cultures of fetal thymocytes rescued V gamma 3 cells from dying. Addition of IL-1, IL-3, IL-5, IL-6, IL-9, TNF-alpha or IFN-gamma was without effect. Phenotypic analysis showed that the alpha-chain of the IL-2 receptor (IL-2R alpha) was expressed by part of the immature V gamma 3 thymocytes, all mature V gamma 3 cells expressed the beta-chain of the IL-2 receptor (IL-2R beta). Addition of anti-IL-2R beta mAb to fetal thymic organ culture (FTOC) resulted in a moderate reduction of the cell number of mature V gamma 3 thymocytes. Addition of anti-IL-2R alpha, anti-IL-4 or anti-IL-7 mAb had no effect. The cell number of mature V gamma 3 cells was highly reduced when both anti-IL-2R beta and anti-IL-7 mAb were added to FTOC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine dependence of V gamma 3 thymocytes: mature but not immature V gamma 3 cells require endogenous IL-2 and IL-7 to survive--evidence for cytokine redundancy. 754 10

The IL-2 receptor (IL-2R) gamma c subunit is also a component of the receptors for IL-4, IL-7, IL-9, and IL-15. The IL-4R and IL-13R appear to share a common subunit, and gamma c was proposed to be this shared subunit. In this study, we have assessed the relative contribution of gamma c to the mouse IL-4R and IL-13R. The MC/9 mast cell line constitutively expresses gamma c and proliferates to IL-4 and IL-13, but only the response to IL-4 was blocked by anti-gamma c mAbs. After transfection of the IL-4- and IL-13-responsive gamma c-negative B9 plasmacytoma with full length (m gamma) or cytoplasmic-tailless gamma c cDNA (m gamma t), only the proliferative response to IL-4 was affected by the surface expression of these gamma c molecules. The inability of m gamma or m gamma t expression to affect IL-13-induced proliferation by B9 indicates that gamma c does not obviously contribute to the IL-13R and does not function as the shared subunit of the IL-4R and IL-13R. This study suggests that there are two distinct IL-4R, one of which is independent of gamma c.
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PMID:The IL-2 receptor gamma c chain does not function as a subunit shared by the IL-4 and IL-13 receptors. Implication for the structure of the IL-4 receptor. 760 26

Human intestinal lymphocytes, particularly intraepithelial lymphocytes, proliferate minimally to some agents, like mitogens and stimuli of the CD3 pathway. This in vitro finding may be due, in part, to a loss of factors found in vivo. Three T-cell growth factors, IL-7, IL-9, and IL-12, were tested for their ability to stimulate the proliferation of intestinal lymphocytes. Both intraepithelial lymphocytes and lamina propria lymphocytes proliferated more vigorously to IL-7 than to IL-9 or IL-12, and only IL-7 increased stimulation through the CD3 pathway. The IL-7-induced response was IL-2-dependent: IL-2 receptors appeared on both intestinal lymphocyte types, and antibody to the IL-2 receptor blocked IL-7-induced proliferation. Both CD4+ and CD8+ T-cell subsets responded to this cytokine as shown by phenotype-depletion experiments and constancy in the CD4/CD8 ratios after culture with IL-7. In addition, the T-cell receptor alpha beta and gamma delta subsets responded equally well to IL-7. This newly described selective proliferative response of intestinal lymphocytes to IL-7, but not to IL-9 or IL-12, requires no preactivation and may enhance growth in vivo.
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PMID:Interleukin-7 activates intestinal lymphocytes. 764 74

Interleukin (IL) 2 signaling requires the dimerization of the IL-2 receptor beta (IL-2R beta) and common gamma (gamma c) chains. The gamma is also a component of the receptors for IL-4, IL-7, and IL-9. To assess the extent and role of the receptor signal transducing system utilizing the gamma c chain on human intestinal epithelial cells, the expression of gamma c, IL-2R beta, and receptor chains specific for IL-4, IL-7, and IL-9 was assessed by reverse transcription-coupled PCR on human intestinal epithelial cell lines and on isolated primary human intestinal epithelial cells. Caco-2, HT-29, and T-84 cells were found to express transcripts for the gamma c and IL-4R chains constitutively. IL-2R beta chain expression was demonstrated in Caco-2 and HT-29 but not in T-84 cells. None of the cell lines expressed mRNA for the IL-2R alpha chain. After stimulation with epidermal growth factor for 24 h Caco-2, HT-29, and T-84 cells expressed transcripts for IL-7R. In addition, Caco-2 and HT-29 cells expressed mRNA for the IL-9R. Receptors for IL-2, IL-4, IL-7, and IL-9 on intestinal epithelial cells lines appeared to be functional; stimulation with these cytokines caused rapid tyrosine phosphorylation of proteins. The relevance of the observations in intestinal epithelial cell lines for intestinal epithelial function in vivo was supported by the demonstration of transcripts for gamma c, IL-2R beta, IL-4R, IL-7R, and IL-9R in primary human intestinal epithelial cells.
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PMID:Human intestinal epithelial cells express functional cytokine receptors sharing the common gamma c chain of the interleukin 2 receptor. 766 94

The third component of the interleukin (IL) 2 receptor, gamma chain, is essential not only for IL-2- but also for IL-4-, IL-7-, IL-9-, and IL-15-induced proliferation of lymphocytes. To elucidate the mechanisms by which the gamma chain is expressed, we have analyzed the promoter region of the gamma chain gene. The 633-base pair fragment upstream of the initiation codon showed the promoter activity in human hematopoietic cell lines, Jurkat and THP-1, when linked to the luciferase gene. With a series of 5'-deletion mutants, the basal promoter activity was found in a fragment from nucleotide 80 to 58 upstream from the RNA start site, including an Ets binding sequence. Treatment of cells with either 12-O-tetradecanoylphorbol-13-acetate or phytohemagglutinin but not forskolin induced transcription from the gamma chain gene promoter. A viral trans-acting transcriptional activator, Tax, of human T-cell leukemia virus type I elevated expression of the gamma chain gene. In contrast, IL-2 decreased transcription from the IL-2 receptor gamma chain promoter. These results suggest that expression of the gamma chain is regulated at the transcription level by extracellular stimuli and may be implicated in immune response.
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PMID:Functional analysis of the human interleukin 2 receptor gamma chain gene promoter. 770 94

The third subunit, the so-called common gamma (gamma c) chain, of the IL-2 receptor is shared among the receptors for IL-2, IL-4, IL-7 and IL-15, and dysfunction of the gamma c chain is thought to cause X-linked severe combined immunodeficiency (XSCID) ascribed to impairment of early T cell development. However, cytokines linked to XSCID are as yet unidentified. A mAb specific for the gamma c chain, TUGm2, profoundly inhibited cell proliferation in response to IL-9. Another mAb, TUGm3, immunoprecipitated [125I]IL-9 cross-linked with either the IL-9 receptor or the gamma c chain. These results demonstrate that the gamma c chain is included in the functional receptor complex for IL-9, which was initially characterized as a T cell growth factor and is essential for IL-9-dependent growth signal transduction.
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PMID:Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex. 771 8

Recent work has shown that T lymphocytes undergo apoptosis upon treatment with the glucocorticoid analogue dexamethasone. These cells can be protected from the effect of dexamethasone by interleukin-2 (IL-2) or IL-4. We were interested in analysing whether a transfected cell dependent on three different lymphokines could be protected by them from the effect of dexamethasone. In addition, we took advantage of our cellular system, in which we expressed intermediate- or high-affinity IL-2R independently, to analyse the role of these receptors in the protection from glucocorticoid-induced apoptosis. In this report we show that IL-2 rescues murine T cells expressing exogenous intermediate- (TS1 beta) or high-affinity (TS1 alpha beta) IL-2 receptor (IL-2R) from dexamethasone-induced apoptosis. This result suggests that intermediate-affinity IL-2R alone can replace high-affinity IL-2R for the protection from the effect of dexamethasone. In addition, IL-4 and IL-9 are rescue-factors, as well as IL-2, of glucocorticoid-treated TS1 beta and TS1 alpha beta cells. Our data suggest that the presence of the alpha-chain of the IL-2R is not required for rescue by IL-2 from the effect of dexamethasone. In addition, we show that proliferation is not required for preventing glucocorticoid-induced apoptosis. This result implies a new role for the intermediate-affinity IL-2R.
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PMID:A role for the intermediate affinity IL-2R in the protection against glucocorticoid-induced apoptosis. 775 Oct 21

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.
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PMID:Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. 797 58

IL-2 regulates growth and differentiation of various types of cells in the immune system via its interaction with IL-2 receptor (IL-2R). The high and intermediate-affinity IL-2Rs, which consist of the alpha beta gamma heterotrimer complex and the beta gamma heterodimer complex, respectively, harbor the function of the intracellular signal transduction, indicating that the beta and gamma chains are indispensable for the signal transduction but not the alpha chain. The reconstitution studies of IL-2Rs with alpha, beta and gamma chain genes demonstrated that each subunit has potential for altering the affinity of the receptor, and the cytoplasmic domains of the beta and gamma chains participate in signal transduction in terms of cell growth, activation of alpha tyrosine kinase and enhancement of c-myc, c-fos and c-jun transcription. The region containing the SH2 homologous sequence of the gamma chain should have a critical function for signal transduction. On the other hand, common subunits are known to be shared among receptors for IL-3, IL-5 and GM-CSF, and receptors for IL-6, LIF, OSM and LIF. We have demonstrated that the monoclonal antibody specific for the IL-2R gamma chain completely inhibited not only IL-2-dependent cell growth but also IL-4-dependent, IL-7-dependent, and IL-9-dependent cell growth, suggesting that the gamma chain is possibly shared among receptors for IL-2, IL-4, IL-7 and IL-9. Impairment of the gamma chain function is considered to be closely related to human XSCID characterized by profound T cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Structure and function of IL-2 receptor subunits]. 802 15


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