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

A protein-tyrosine phosphatase LC-PTP is preferentially expressed in hematopoietic cells and is an early response gene in lymphokine stimulated cells. Here, we found the LC-PTP mRNA induction by IL-2 was markedly inhibited by several tyrosine kinase inhibitors. The induction required both the acidic and serine-rich regions of the IL-2 receptor beta chain (IL-2R beta) in mouse IL-3-dependent pro-B BAF-B03 transfectants. This is strikingly different from the induction of c-myc gene expression, which requires the serine-rich region alone. In addition, overexpression of activated-Lck or -Raf kinases resulted in augmented LC-PTP mRNA expression in myeloid cell line 32D transfectants. Considering the previous findings that the acidic region of the IL-2R beta is responsible for association with Lck and activation of Raf kinase, IL-2-induced expression of LC-PTP mRNA may be primarily transduced through a Lck-Raf mediated signaling pathway.
 ...
PMID:IL-2-induced gene expression of protein-tyrosine phosphatase LC-PTP requires acidic and serine-rich regions within IL-2 receptor beta chain. 755 30

The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains. 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 report that Syk protein tyrosine kinase (PTK) is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2R beta chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c-myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.
 ...
PMID:Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway. 760 Mar 4

Stimulation of activated T cells with interleukin-2 (IL-2) results in the tyrosine phosphorylation of several intracellular proteins. The present studies demonstrate that IL-2 stimulation induces phosphorylation of the src homology 2 domain-containing protein, p52shc, on both tyrosine and serine residues. The level of p52shc phosphorylation was maximal within 5 min after growth factor addition and declined gradually thereafter. In addition, anti-Shc immunoprecipitates from IL-2-stimulated T cells contained a co-precipitating protein tyrosine kinase (PTK) activity that phosphorylated p52shc on tyrosine residues in immune complex kinase assays. These results demonstrate that p52shc is an early substrate for IL-2 receptor-coupled PTK activity(s) and suggest that this protein may be involved in the transduction of PTK-dependent regulatory signals in IL-2-stimulated T cells.
 ...
PMID:Interleukin-2-induced tyrosine phosphorylation of p52shc in T lymphocytes. 768 28

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.
 ...
PMID:Serine-rich region of the IL-2 receptor beta-chain is required for activation of phosphatidylinositol 3-kinase. 802 55

Protooncogenes are the normal forms of cellular genes that when altered in their expression or coding sequences can contribute to neoplastic transformation. As these genes often are important for normal cellular growth control, we explored the possibility that protein kinases encoded by particular protooncogenes could participate in signal transduction pathways regulated by the T cell growth factor, interleukin-2 (IL-2). In this review we summarize our findings to date regarding Raf-1, a serine/threonine-specific kinase that becomes phosphorylated on tyrosine residues and enzymatically activated in response to IL-2 stimulation. In addition, we describe our investigations of Lck and Lyn, two closely related protein tyrosine kinases of the src gene family that physically associate with the IL-2 receptor complex and whose activities are regulated by IL-2 in at least some T cells and B cells, respectively.
 ...
PMID:Protooncogene-encoded protein kinases in interleukin-2 signal transduction. 826 Jun 49

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.
 ...
PMID:p56lck phosphorylation by Ca2+/calmodulin-dependent protein kinase type II. 829 50

Previous studies demonstrate that p56lck, a member of the src-family of protein tyrosine kinases (PTKs), can physically associate with the interleukin-2 (IL-2) receptor beta chain (IL-2R beta) and that IL-2 receptor engagement stimulates p56lck activity. To examine the mechanisms underlying p56lck PTK activation by IL-2, we established a mouse pro-B cell line, BAF-B03, expressing both IL-2R beta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2R beta chain lacking an 'acidic' region of the cytoplasmic domain, previously shown to be essential for association with p56lck, fail to induce p56lck PTK activation upon IL-2 stimulation. This suggests that the association of p56lck with the IL-2R beta chain, despite its low stoichiometry, is required for the activation of cellular p56lck PTK upon IL-2 stimulation. Intriguingly, BAF-B03 cells expressing an IL-2R beta chain which lacks a different cytoplasmic region, the 'serine-rich' region, also fail to activate p56lck in response to IL-2. Hence, physical association of p56lck with the IL-2R beta chain is not by itself sufficient to permit IL-2-mediated regulation of this PTK. Additional experiments suggest that one result of PTK activation is the accumulation of c-fos and c-jun transcripts.
 ...
PMID:Association of p56lck with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56lck. 844 Feb 63

Variations in protein phosphorylation provide the predominant means of enzymatic regulation now known in biological systems, especially in the regulation of signal transduction from cell surface receptors. Analysis of these signaling pathways has proceeded especially rapidly in lymphocytes, in part because these cells can be isolated with relative ease and can in many cases be maintained in vitro for prolonged periods as clonal populations. During the past few years, both biochemical and genetic evidence has been adduced indicating that the antigen receptors of T and B lymphocytes associate functionally with nonreceptor protein tyrosine kinases. Similar data implicate protein tyrosine kinases in signaling from the CD4 and CD8 coreceptors and the beta chain of the IL-2 receptor. Protein serine/threonine kinases and several different phosphatases also participate in the intracellular propagation of antigen receptor-derived signals. Here we review the lymphocyte surface receptors that are believed to act by altering protein phosphorylation, the kinases and phosphatases that are believed to regulate signal transduction in lymphocytes, and the implications of these results for the broader study of cell signaling mechanisms.
 ...
PMID:Regulation of lymphocyte function by protein phosphorylation. 847 69

The biological activity of all recombinant forms of interleukin-2 (IL-2) is based upon an in vitro lymphocyte proliferation assay and measured in international units (IU). Numerous in vitro investigations have suggested that there may be different cellular effects of recombinant human IL-2 retaining the natural sequence (nIL-2) as compared to another recombinant form containing a serine substitution at amino acid position 125 ([Ser]IL-2). In the present study we investigated whether nIL-2 and [Ser]IL-2 cause similar patterns of systemic toxicities. C57BL/6 mice were treated with identical doses of either nIL-2 or [Ser]IL-2, as measured in IU, for 3 days and had blood and tissues removed for analysis of lymphocyte activation and organ dysfunction. The administration of nIL-2 had considerably greater effects on lymphocyte activation than did [Ser]IL-2, causing much greater up-regulation of the alpha subunit of the IL-2 receptor and the adhesion molecule lymphocyte function-associated antigen-1. Furthermore, nIL-2 induced more organ edema than did [Ser]IL-2 and caused hepatocellular injury, which was absent in mice treated with [Ser]IL-2. These data demonstrate that equivalent doses, measured in IU, of nIL-2 and [Ser]IL-2 have profoundly different effects on the induction of organ toxicity, suggesting that the IU standard may not be appropriate for the measurement of many in vivo biological activities.
 ...
PMID:Distinct biological activities of recombinant forms of human interleukin-2 in vivo. 906 4

Stimulation of human CD4+ T cell lines with interleukin 2 (IL-2) induces tyrosine, serine and threonine phosphorylation of a series of proteins involved in the IL-2 receptor (IL-2R) signaling pathway. Here, we examined whether IL-2 induces changes in the activity of protein serine/threonine phosphatases in antigen specific, CD4+ human T cell lines. Using inhibitors of protein phosphatases 1 (PP1, PP2A, and PP2B, we provide evidence, that IL-2 induces a downregulation of PP activity in the cytoplasmic/membrane fraction. Thus, IL-2R ligation for 30 min triggers a 16 percent decrease in total PP2A activity (p < 0.0005, n = 17) and a seven percent decrease in PP1 activity (p < 0.00005, n = 17). Cytokine-induced downregulation of PP2A activity reaches a maximum 60 min after IL-2R ligation, and returns to baseline levels within two hours. Downregulation of PPI activity reaches a maximum after 30 min and is largely reversed one hour after IL-2 stimulation. As determined from immunoblotting experiments using a specific anti-PP1 or anti-PP2A antibody, the amount of PPI and PP2A recovered from cytosolic/membrane fraction remains unchanged after IL-2 treatment suggesting that the drop in PP1/PP2A activity might be due to a regulatory change rather than to a change in the amount of PP1 and PP2A. In conclusion, we provide evidence, for the first time, that IL-2 induces a transient downregulation of PP2A activity in T cells. In addition, our findings indicate that cytoplasmic PP1 activity is transiently downregulated following IL-2R ligation in antigen-specific, human CD4+ T cells.
 ...
PMID:Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells. 909 29


<< Previous 1 2 3 4 5 Next >>