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)

Tac antigen, the receptor for human interleukin 2 (IL-2), contains in its intracytoplasmic region a serine residue (Ser-247) that is seemingly the predominant site of protein kinase C-mediated phosphorylation. A number of studies on growth factor receptors have suggested the importance of phosphorylation in receptor structure, function, and regulation. In this study, we generated site-directed mutations in the Tac antigen cDNA to generate mutant receptors in which Ser-247 or Thr-250, a probable site of minor phosphorylation, was replaced with another amino acid that is not accessible to phosphorylation. Study of the expression of these mutant genes in a T-lymphoid cell line has provided no evidence as to the essential role of the above-mentioned residues in determining the degree of receptor affinity, its ability for signal transduction, and phorbol ester-mediated regulation of the receptor. Our results strongly suggest the existence of an IL-2 receptor "complex" in which the Tac antigen is associated with another molecule(s) that is involved in receptor structure, function, and regulation.
Proc Natl Acad Sci U S A 1986 Dec
PMID:Intracytoplasmic phosphorylation sites of Tac antigen (p55) are not essential for the conformation, function, and regulation of the human interleukin 2 receptor. 309 87

The interleukin 2 (IL-2) receptor system plays a key role in the T-cell immune response. Although IL-2 binding was reported to be restricted to the Tac peptide, we have identified an IL-2 binding peptide that does not react with anti-human IL-2 receptor monoclonal antibodies, including anti-Tac on MLA 144, a gibbon ape T-cell line. The MLA 144 cell line expressed 6800 IL-2 binding sites per cell with a low (Kd = 14 nM) affinity for human recombinant IL-2. Using cross-linking methodology, we demonstrated that the IL-2 binding peptide on MLA 144 is larger (Mr 75,000) than the Tac peptide, which has a Mr of 55,000. An IL-2 binding peptide of similar size (Mr 75,000) was also identified in addition to the Tac peptide (Mr 54,000-57,000) on Hut 102, a human T-cell lymphotrophic virus I-induced T-cell leukemia line, and phytohemagglutinin-activated normal human and gibbon ape lymphoblasts. Anti-Tac antibody did not block the binding of 125I-labeled IL-2 to MLA 144 cells. However, this antibody abolished the binding of 125I-labeled IL-2 not only to the Tac peptide on Hut 102 cells and normal lymphoblasts but also to the Mr 75,000 IL-2 binding peptide, suggesting that this latter peptide is associated with the Tac peptide to form the high-affinity IL-2 receptor complex.
Proc Natl Acad Sci U S A 1986 Dec
PMID:Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. 309 89

1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, suppressed interleukin 2 (IL-2) production and IL-2 receptor (IL-2R) expression of the human leukemic T-cell line, Jurkat, induced by 12-O-tetradecanoyl-phorbol-13-acetate and phytohemagglutinin-P. This effect was significant at 5 microM H-7 without loss of cell viability. Such activity was not observed with N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), a potent inhibitor of cGMP- and cAMP-dependent kinases, and a weak inhibitor of Ca2+-phospholipid-dependent protein kinase (protein kinase C). These findings suggest that protein kinase C is more closely associated with IL-2 receptor expression and IL-2 production of T cells than cGMP- or cAMP-dependent kinases. In addition, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, suppressed both IL-2 production and IL-2R expression. Cycrosporin A (Cy A), a potent immunosuppressive drug, markedly inhibited IL-2 production of Jurkat cells whereas it did not affect the IL-2R expression. Thus, the mechanism of action of Cy A appears to differ from that of the protein kinase inhibitor, H-7, and the calmodulin inhibitor, W-7.
Cell Immunol 1986 Dec
PMID:Inhibitors of IL-2 production and IL-2 receptor expression in human leukemic T-cell line, Jurkat. 310 62

We investigated the expression of the interleukin-2 (IL-2) receptor on phytohaemagglutin-stimulated peripheral blood lymphocytes from homosexual men with persistent generalized lymphadenopathy, the prodrome of the acquired immune deficiency syndrome. The subjects were positive for antibody against human T-cell lymphotropic virus III. Using two-colour fluorescence flow cytometry, IL-2 receptor expression was determined on both the CD4- and CD8-positive lymphocyte subpopulations. After 48 hr of stimulation, expression of the IL-2 receptor on both T-cell subsets was significantly increased in lymphadenopathy patients as compared to values in heterosexual age-matched controls; this difference was less after 72 hr of stimulation. Results from two AIDS patients were within the normal range. IL-2 production was significantly reduced in both lymphadenopathy and AIDS patients as compared to values in heterosexual controls. We conclude that a defect in IL-2 production is associated with human T-cell lymphotropic virus III infection, but that the expression of the IL-2 receptor on T cells is not greatly affected.
Immunology 1986 Dec
PMID:Increased interleukin-2 receptor expression after mitogen stimulation on CD4- and CD8-positive lymphocytes and decreased interleukin-2 production in HTLV-III antibody-positive symptomatic individuals. 310 Apr 39

The human interleukin-2 (IL-2) receptor was quantitatively cleaved into two large disulfide-bonded fragments by either trypsin or endoproteinase lys-C (endo lys-C). The smaller fragment contains both N-linked oligosaccharides found in the intact receptor and is derived from the amino terminus of the molecule. The larger proteolytic fragment was metabolically labeled with 32PO4 and represents the carboxy terminus. The predicted cleavage sites of both enzymes lie in the region of the molecule encoded by exon 3. This pattern of limited proteolysis provides biochemical evidence that the extracellular region of the receptor is organized into two domains. This supports a structural model of the receptor in which the regions of internal homology encoded by exons 2 and 4 form independent disulfide-bonded domains connected by a hydrophilic segment. To determine the role of these domains in IL-2 binding, [125I]IL-2 was chemically cross-linked to the proteolytically cleaved receptor on the cell surface. The 125I-labeled complex obtained displayed N-linked oligosaccharides and had an Mr consistent with one molecule of IL-2 cross-linked to the smaller proteolytic fragment of the receptor. Thus, the amino-terminal domain of the IL-2 receptor appears to form an integral part of the IL-2 binding site.
EMBO J 1986 Dec 01
PMID:Evidence for two extracellular domains in the human interleukin-2 receptor: localization of IL-2 binding. 310 28

These studies described were designed to determine whether interleukin 2 (IL-2) inhibits lymphocyte migration. The human lymphoblastoid cell line QIMR-WIL was used as an indicator of lymphocyte migration inhibition. Interleukin 2 inhibited QIMR-WIL migration in a dose-dependent manner, high doses of IL-2 (100 units) being strongly inhibitory, and low doses (12.5 units) less inhibitory. Purified natural IL-2 and recombinant IL-2 both inhibited QIMR-WIL migration. The effect of IL-2 on lymphocyte migration was specific. When the IL-2 receptors were blocked with anti-Tac (anti-IL-2 receptor) antibodies, the inhibitory effect of IL-2 was significantly reduced. Similarly antibody to IL-2 blocked the inhibitory effect of IL-2. Lymph node lymphocytes were also used as indicator cells in migration studies and IL-2 inhibited their motility. These data suggest a role for IL-2 in inhibiting lymphocyte migration similar to that of lymphocyte migration inhibition factor produced by antigen- or mitogen-stimulated T lymphocytes. While it is widely recognized that lymphocyte motility can be reduced by lymphocyte migration inhibition factor, these data indicate that IL-2 can also reduce lymphocyte motility.
Clin Exp Immunol 1986 Dec
PMID:Inhibition of lymphocyte motility by interleukin 2. 310 35

We made a mutant cDNA clone of the human interleukin-2 (IL-2) receptor by introducing a termination codon at the eighth amino acid residue upstream from the putative transmembrane region. Ltk- cells were transfected by this mutant cDNA and cell-lines secreting the extracytoplasmic portion of the IL-2 receptor were established. The artificial secretory molecule of the IL-2 receptor named "bottom-less" receptor was able to react with anti-Tac antibody and to bind IL-2. We purified the bottom-less receptor to homogeneity by affinity chromatography using an IL-2-Sepharose column. The affinity (Kd value) of the 125I-labeled bottom-less receptor to IL-2 coupled to Sepharose beads was estimated to be 4.5 microM. All these results confirm the putative membrane topology of the IL-2 receptor based on the primary structure, and suggest that the bottom-less receptor may maintain the basic structure and function of the extracytoplasmic portion of the IL-2 receptor.
Mol Biol Med 1986 Dec
PMID:Production and characterization of the extracytoplasmic portion of the human interleukin-2 receptor. 311 9

Although cyclosporin A (Cy A) has been widely used clinically as a potent suppressor of organ allograft rejection and has been shown to block T lymphocyte activation in vitro by inhibiting the generation of interleukin 2 (IL-2) and other lymphokines, little direct evidence is available to support the view that the immunosuppressive effects of Cy A in vivo are mediated by a similar inhibition of the autocrine lymphokine cascade. We have used a quantitative assay for the assessment of the role of the IL-2/IL-2 receptor system in the activation of the draining popliteal lymph node population after the injection of allogeneic cells in the footpad to define the effects of Cy A on the early events of lymphocyte activation in vivo and to compare them with the effects of Cy A on lymphocyte activation in vitro. The administration of Cy A in vivo had no effect on alloantigen-induced increases in cell size, percentage of cells expressing the IL-2 receptor, the spontaneous or IL-2-driven proliferation of freshly explanted cells, or the induction of cytotoxic T lymphocyte activity. These findings raise major questions about the mechanism of action of Cy A in vivo and suggest that more experimentation is required to probe the mechanisms of Cy A-induced suppression of the response to allografts.
J Immunol 1987 Dec 01
PMID:Mechanism of action of cyclosporin A in vivo. I. Cyclosporin A fails to inhibit T lymphocyte activation in response to alloantigens. 311 12

During the growth of interleukin 2 (IL-2)-dependent T cells IL-2 binding is followed by internalization of the complex between IL-2 and the high affinity IL-2 receptor (HA-IL-2R). The respective role of IL-2 binding to HA-IL-2R and internalization of the complex has been examined. Monoclonal antibody 7D4 (IgM) blocks IL-2-dependent T cell growth although it does not affect IL-2 binding to HA-IL-2R. We show here that 7D4 inhibits T cell growth by blocking IL-2 internalization by HA-IL-2R. In contrast, Fab fragments prepared from 7D4 neither block IL-2 internalization nor inhibit T cell growth. Monoclonal 5A2, that recognizes an epitope related to the IL-2 binding site as well as its Fab fragment, inhibits T cell growth and IL-2 internalization. Monoclonal antibody 7D4, because of its pentameric structure, probably aggregates the IL-2R at the T cell surface and therefore prevents it internalization. The data presented in this paper suggest that simple occupancy of HA-IL-2R by IL-2 is not sufficient to transduce the T cell growth signal; this signal is transmitted only after internalization of the IL-2/HA-IL-2R complex.
J Immunol 1987 Dec 01
PMID:Internalization of interleukin 2 (IL-2) by high affinity IL-2 receptors is required for the growth of IL-2-dependent T cell lines. 311 13

CD3-4-8- and unfractionated thymocytes were compared for their capacity to proliferate, to express interleukin 2 (IL-2) receptor, and to secret IL-2. Phorbol ester and Ca2+ ionophore were used as mitogens. CD3-4-8- thymocytes responded vigorously when stimulated with phorbol ester in the presence of IL-2 or in combination with Ca2+ ionophore. In contrast, unfractionated thymocytes responded weakly when stimulated with either of these mitogens. Surprisingly, however, the stimulation of these populations with either phorbol ester plus IL-2 or phorbol ester plus ionophore induced a high and similar level of IL-2 receptor expression in both thymocyte populations. A similar level of IL-2 secretion in both populations was also obtained when they were stimulated with a combination of phorbol ester plus ionophore. These results suggest that during the maturation process, the majority of thymocytes lose their capacity to be activated by some mitogens, although they maintain their capacity to secrete IL-2 and to express the IL-2 receptor.
Proc Natl Acad Sci U S A 1987 Dec
PMID:Unfractionated human thymocytes have a lower proliferative capacity than CD3-4-8- ones but have a similar capacity for expression of interleukin 2 receptors and production of interleukin 2. 312 Jan 95


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