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)

Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 microCi/microgram (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target alpha radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of alpha-particle-emitting radionuclides in immunotherapy.
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PMID:Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy. 307 13

In the immune system, T-lymphocyte proliferation depends on interleukin 2 [IL-2 (T-cell growth factor)] interaction with specific receptors. In this study we show that IL-2 can specifically inhibit the proliferation of neonatal rat oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium (oligodendrocyte-defined medium; ODM). IL-2 inhibited both [3H]thymidine incorporation and increase in cell number. Specificity was shown by precipitating IL-2 activity with anti-IL-2 antiserum. Furthermore, growth inhibition depended on the expression of Tac (an anti-IL-2 receptor monoclonal antibody)-positive receptors (IL-2 receptor). When cells were cultured in the presence of IL-2, both Tac-positive staining and growth inhibition were no longer expressed. The addition of interleukin 1 had no effect on [3H]thymidine incorporation or changes in cell number. However, when IL-1 was subsequently added together with IL-2, Tac expression and IL-2-mediated inhibition of cell proliferation was induced. This inhibitory effect was not due to a sensitive subpopulation because greater than 90% of the culture was Tac positive. Taken together, these data show that IL-2 can specifically inhibit oligodendrocyte proliferation and acts via Tac-positive receptors.
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PMID:Interleukin 2 mediates the inhibition of oligodendrocyte progenitor cell proliferation in vitro. 309 48

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.
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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

A B cell line derived from a human nodular lymphocytic lymphoma (Brill-Symmers) was shown to be dependent on the presence of a low molecular weight B cell growth factor (BCGF) for its growth in vitro. The caryotype was normal and no contamination with Epstein-Barr virus (EBV) could be detected. These cells did not respond to recombinant gamma interferon or to recombinant human interleukin 2 (IL-2), although they displayed a weak density of IL-2 receptor sites. They were both responsive to and dependent on BCGF for their multiplication in vitro. Furthermore, the putative receptor for this growth factor (CD23) was detected on these cells and the BCGF-dependent proliferation could be blocked by a monoclonal anti-CD23 antibody. A tumour-derived cell line like this provides an interesting model for studying the mechanisms regulating B cell growth and the early events leading to the process of B cell immortalization.
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PMID:A B cell growth factor-dependent cell line derived from a human lymphocytic nodular lymphoma. 311 29

PHA activated human peripheral blood mononuclear cells (MNC) were incubated with human interleukin 2 (IL-2) in the absence or in the presence of 10(-6)-10(-9) M hydrocortisone (HC). HC suppressed the proliferative response of the activated MNC to highly purified human leucocyte IL-2 in a dose dependent manner. This suppression was in full accordance with an inhibition of the IL-2 binding capacity, whereby the high affinity binding sites were reduced by 85%, while the low affinity sites were less affected. The mechanism by which HC inhibits the binding of IL-2 is still unknown. Evidence is presented that HC binds only weakly to IL-2. We conclude that HC interferes with the IL-2 binding by modulating the binding and/or signal processing function of the IL-2 receptor.
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PMID:Corticosteroid-interleukin 2 interactions: inhibition of binding of interleukin 2 to interleukin 2 receptors. 311 40

A cDNA clone for human interleukin 2 (IL-2) has been fused to the 5' end of a modified Pseudomonas exotoxin (PE) gene that lacks the sequences encoding the cell recognition domain. The chimeric protein IL-2-PE40 was produced in Escherichia coli. It was extremely toxic to IL-2 receptor-positive cells but had no measurable effect on cells lacking the IL-2 receptor. IL-2-PE40 might be a useful cytotoxic agent in the treatment of diseases involving IL-2 receptor-positive cells and in the treatment of allograft rejection.
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PMID:Cytotoxic activity of an interleukin 2-Pseudomonas exotoxin chimeric protein produced in Escherichia coli. 312 99

An increase in the isometric developed tension (IDT) of isolated rat atria was observed shortly after the addition of human interleukin 2 (IL-2) to the organ preparation with subthreshold concentrations of either arachidonate (AA, 1.98 X 10(-6)M) or the calcium ionophore A 23187 (1.9 X 10(-6)M). Both natural purified IL-2 (nIL-2) and yeast recombinant IL-2 (rIL-2) were active in this experimental system. It was determined that this lymphokine was active at 2 X 10(-11)M, considering as a reference the specific activity of rIL-2. Anti-IL-2 monoclonal antibody (anti-IL-2 MAb) abolished this reaction. Inhibition of atrial phospholipase C activity by nitrocarboxyphenyl N,N-diphenylcarbamate (NCDC, 5 X 10(-6)M) prevented the development of the inotropic positive effect of IL-2 in the presence of either AA or A 23187. The synthetic diacylglyceride 1-oleoyl, 2-acetyl-glycerol (OAG) replaced the IL-2 as stimulatory signal but NCDC had no effect on the reaction. The results suggest that IL-2 can alter the physiologic behaviour of the heart and that its mechanism of action is probably similar to the one proposed for other IL-2 targets (IL-2 receptor-positive T lymphocytes, T cell lines).
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PMID:Interleukin 2 stimulates heart contractility in the presence of exogenous arachidonate or the calcium ionophore A 23187. 312 71

We have genetically replaced the diphtheria toxin receptor binding domain with a DNA insert encoding the T-cell growth factor interleukin-2 (IL-2). The toxin-related IL-2 fusion gene encodes a 70,586 dalton protein, pro-IL-2-toxin. The mature form of IL-2-toxin is exported to the periplasmic space of recombinant Escherichia coli and has a molecular weight of 68,086. IL-2-toxin has been partially purified from periplasmic extracts of recombinant E. coli, and it is shown to contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. The chimeric toxin is targeted toward IL-2 receptor bearing T-cells in vitro.
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PMID:Cell receptor specific targeted toxins: genetic construction and characterization of an interleukin 2 diphtheria toxin-related fusion protein. 313 72

We have genetically replaced the diphtheria toxin receptor binding domain with a synthetic gene encoding interleukin-2 (IL-2) and a translational stop signal. The diphtheria toxin-related T-cell growth factor fusion gene encodes a 70 586-d polypeptide, pro-IL-2-toxin. The mature form of IL-2-toxin has a deduced mol. wt of 68,086 and is shown to be exported to the periplasmic compartment of Escherichia coli (pABI508), and contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. IL-2-toxin has been purified from periplasmic extracts of recombinant strains of E. coli (pABI508) by immunoaffinity chromatography using immobilized anti-IL-2. The purified chimeric toxin is shown to selectively inhibit protein synthesis in IL-2 receptor bearing targeted cells, whereas cell lines which do not express the IL-2 receptor are resistant to IL-2-toxin action.
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PMID:Diphtheria toxin receptor binding domain substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein. 333 1

We have used cDNAs for the human interleukin 2 (IL-2) receptor to study IL-2 receptor gene expression in normal activated T cells. Resting T cells do not contain detectable IL-2 receptor mRNA. Within 1 hr after stimulation with phytohemagglutinin (PHA), a large, presumably nuclear precursor RNA species is seen, which then gradually disappears. Mature IL-2 receptor mRNA forms appear within 8 hr after stimulation, reach peak levels between 8 and 24 hr, and then decline. Thus, in PHA-activated lymphocytes the rise and fall in IL-2 receptor mRNA levels precede by more than 24 hr the peak and decline of IL-2 receptor protein expression occurring at the cell surface. 4 beta-Phorbol 12-myristate 13-acetate (PMA) also stimulates IL-2 receptor mRNA and protein expression by T cells. Combinations of optimal concentrations of PHA and PMA produce an additive effect on IL-2 receptor mRNA levels, suggesting that PHA and PMA may induce IL-2 receptor gene expression through different, complementary mechanisms. Nuclease S1-protection assays indicate that IL-2 receptor mRNAs may differ in length due to the use of three different polyadenylylation signals. Further, these assays demonstrate the presence of transcripts that lack a 216-base segment within the protein-coding region and thus do not encode a functional IL-2 receptor. Nuclear transcription assays indicate that the increase in IL-2 receptor mRNA is reflected at the level of transcription. Thus, IL-2 receptor gene regulation controls IL-2 receptor expression at the cell surface and is intimately linked to the control of T-cell proliferation.
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PMID:Interleukin 2 receptor gene expression in normal human T lymphocytes. 392 55


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