Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, interleukin 2 (IL-2) has been shown to induce increased activity of the p56lck protein-tyrosine kinase (PTK) in T-cell and natural killer cell lines, and evidence for a direct interaction between the p75 subunit of the IL-2 receptor (IL-2R) and this src-family kinase has been reported. Though these findings suggest a central role for lck in IL-2 signal transduction, one problem with this idea is that not all IL-2-responsive cells express the lck gene. For this reason, we examined the effects of IL-2 on the activity of src-like kinases in a pro-B cell line, F7, that lacks p56lck but that displays high-affinity IL-2Rs and vigorously proliferates in response to this lymphokine. Of the eight known src-family PTKs, F7 cells were shown to contain only p53/56lyn, p59fyn, and a small amount of p62yes. Stimulation of resting F7 cells with IL-2 induced a rapid (detectable within 1 min and maximal at 15 min) and concentration-dependent increase in the specific activity of p53/56lyn kinase, as assessed by in vitro kinase assays. This effect of IL-2 on p53/56lyn kinase was specific, since no IL-2-inducible changes were detected in the activities of the p59fyn and p62yes kinases. Furthermore, by using a monoclonal antibody specific for the approximately 75-kDa beta subunit of the IL-2R (referred to as p75/IL-2R beta), evidence for physical association between the lyn kinase and the IL-2R complex was obtained, in that a small proportion of the p53/56lyn kinase in F7 cells, but no detectable p59fyn kinase, was coimmunoprecipitated with p75/IL-2R beta. When combined with the recent evidence that IL-2 regulates p56lck in T cells, these results indicate that some flexibility exists in the ability of various src-like PTKs to participate in IL-2 signal transduction mechanisms and raise the possibility that lineage-specific (T-versus B-cell) responses to IL-2 may be determined at least in part by the repertoire of src-like PTKs expressed in the cell.
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PMID:Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line. 155 73

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

Staphylococcal enterotoxins (SE) stimulate T cells expressing the appropriate variable region beta chain of (V beta) T-cell receptors and have been implicated in the pathogenesis of several autoimmune diseases. Depending on costimulatory signals, SE induce either proliferation or anergy in T cells. In addition, SE can induce an interleukin-2 (IL-2) nonresponsive state and apoptosis. Here, we show that SE induce dynamic changes in the expression of and signal transduction through the IL-2 receptor (IL-2R) beta and gamma chains (IL-2R beta and IL-2R gamma) in human antigen-specific CD4+ T-cell lines. Thus, after 4 hr of exposure to SEA and SEB, the expression of IL-2R beta was down-regulated, IL-2R gamma was slightly up-regulated, while IL-2R alpha remained largely unaffected. The changes in the composition of IL-2Rs were accompanied by inhibition of IL-2-induced tyrosine phosphorylation of the Janus protein-tyrosine kinase 3 (Jak3) and signal transducers and activators of transcription called Stat3 and Stat5. In parallel experiments, IL-2-driven proliferation was inhibited significantly. After 16 hr of exposure to SE, the expression of IL-2R beta remained low, while that of IL2R alpha and IL2R gamma was further up-regulated, and ligand-induced tyrosine phosphorylation of Jak3 and Stat proteins was partly normalized. Yet, IL-2-driven proliferation remained profoundly inhibited, suggesting that signaling events other than Jak3/Stat activation had also been changed following SE stimulation. In conclusion, our data suggest that SE can modulate IL-2R expression and signal transduction involving the Jak/Stat pathway in CD4+ T-cell lines.
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PMID:Staphylococcal enterotoxins modulate interleukin 2 receptor expression and ligand-induced tyrosine phosphorylation of the Janus protein-tyrosine kinase 3 (Jak3) and signal transducers and activators of transcription (Stat proteins). 747 24

The proliferation of activated T lymphocytes is critically dependent on the binding of the T-cell growth factors, interleukin (IL)-2 and IL-4, to distinct but evolutionarily related cell surface receptors. Previous results suggest that the IL-2 receptor (IL-2R) and IL-4R are coupled to both overlapping and distinct intracellular signaling pathways in T lymphocytes. In this study, we demonstrate that activation of Janus tyrosine kinases (JAKs) and STAT transcription factors is rapidly induced by exposure of factor-dependent murine T-cell lines to IL-2 or IL-4. Both IL-2 and IL-4 stimulated the rapid activation of JAK1 and JAK3, whereas JAK2 activity was unaffected by either cytokine. These responses were accompanied by the appearance in cell nuclei of 3 DNA binding activities that recognized a high-affinity binding site for STAT factors. In transient transfection assays, this STAT factor target sequence conferred IL-2 and IL-4 inducibility on a synthetic luciferase reporter gene. Antibody supershifting experiments indicated that IL-2 induces the formation of STAT dimers containing STAT3 and STAT1 alpha. Although IL-4 also activated STAT1 alpha, the major IL4-induced STAT factor is not STAT3 and remains undefined. Pretreatment of the T-cells with the protein-tyrosine kinase inhibitor herbimycin A blocked both the nuclear translocation of STAT factors and STAT-dependent reporter gene transcription. Immunoblot analyses confirmed that cytoplasmic STAT3 was heavily phosphorylated on tyrosine in IL-2-stimulated cells, and that phosphorylated STAT3 appeared in the nuclei of these cells. These results indicate that identical JAKs and partially overlapping sets of STATs are activated by IL-2 and IL-4 in T lymphocytes.
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PMID:Protein-tyrosine kinase-dependent activation of STAT transcription factors in interleukin-2- or interleukin-4-stimulated T lymphocytes. 774 3

The intracellular portion of the IL-2 receptor (IL-2R) signal transducing beta-chain contains a distinct region, designated "serine-rich," which encompasses sequences required for IL-2-mediated cell growth. Although the receptor does not possess intrinsic protein-tyrosine kinase activity, IL-2 binding induces activation of intracellular protein-tyrosine kinases. Activation of many protein-tyrosine kinases leads to activation of phosphatidylinositol 3-kinase (PI 3-kinase). IL-2 binding also induces activation of PI 3-kinase. To study the interaction of PI 3-kinase with the IL-2 receptor beta-chain we analyzed PI 3-kinase activity in cells which express the wild type and mutant beta-chain. IL-2 mediated an increase in association with PI 3-kinase activity and protein in immunoprecipitates from cells expressing mitogenically competent receptors. PI 3-kinase products also increased in response to IL-2 in these cells. Deletion of the beta-chain serine-rich region abolished IL-2-mediated mitogenesis and cells expressing this mutant failed to activate PI 3-kinase. The interaction of the IL-2 receptor with an intracellular tyrosine kinase, lck, has been mapped to the acidic-rich region of the beta-chain. Cells which express the beta-chain lacking the acidic-rich region grow in the presence of IL-2 and had IL-2-dependent activation of PI 3-kinase. Activation of PI 3-kinase in response to IL-2 was not abolished by treatment of cells with rapamicin and occurred only in cells which express mitogenically competent receptors. The results presented in this study suggest that IL-2-mediated PI 3-kinase activation occurs by a mechanism distinct from interaction with the lck protein-tyrosine kinase.
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PMID:Serine-rich region of the IL-2 receptor beta-chain is required for activation of phosphatidylinositol 3-kinase. 802 55

Here, we have studied the activity of a novel protein-tyrosine kinase inhibitor that is selective for the Src family of tyrosine kinases. We have focused our study on the effects of this compound on T cell receptor-induced T cell activation, a process dependent on the activity of the Src kinases Lck and FynT. This compound is a nanomolar inhibitor of Lck and FynT, inhibits anti-CD3-induced protein-tyrosine kinase activity in T cells, demonstrates selectivity for Lck and FynT over ZAP-70, and preferentially inhibits T cell receptor-dependent anti-CD3-induced T cell proliferation over non-T cell receptor-dependent phorbol 12-myristate 13-acetate/interleukin-2 (IL-2)-induced T cell proliferation. Interestingly, this compound selectively inhibits the induction of the IL-2 gene, but not the granulocyte-macrophage colony-stimulating factor or IL-2 receptor genes. This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP-70 in T cell activation as well as the role of other Src family kinases in receptor function.
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PMID:Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. 855 75