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)

Influences of methionine enkephalin (met-enk) on delayed hypersensitivity (DH) against 2,4-dinitrofluoro-benzene (DNFB) and interleukin-2 (IL-2) production of mouse lymphocytes were examined. Met-enk enhanced the DH response to ear challenge when mice were treated with met-enk beginning at the same time as cpicutaneous sensitization with DNFB but not after being sensitized. When met-enk (10 nmol.L-1-100 mumol.L-1) was included in Con A-stimulated lymphocyte cultures, the IL-2 production increased in a concentration-dependent manner. Furthermore, in vivo treatment with met-enk also increased IL-2 production of splenocytes, and the enhancement of IL-2 production was parallel to that of lymphocyte proliferation. However, met-enk 10 nmol.L-1 had no effect on IL-2 receptor expression on thymocytes, splenocytes, and gut-associated lymphocytes. The data suggested that the stimulative effect of met-enk on lymphocytes may be mediated through the increase of IL-2, but not through the IL-2 receptor expression.
 ...
PMID:Influence of methionine-enkephalin on interleukin-2 production and interleukin-2 receptor expression. 159 29

Recent data suggest that basophils express receptors for a variety of lymphokines. In this study we present the biochemical characterization of the interleukin-2 (IL-2) receptor on the basophil surface membrane. Highly enriched populations (purity: 92% to 99%) of blood basophils were obtained from chronic granulocytic leukemia (CGL) patients (n = 3) by negative selection using monoclonal antibodies (MoAbs) and complement. CGL basophils were found to bind CD25 MoAbs (n = 4) directed against different epitopes of the 55- to 60-Kd subunit of the IL-2 receptor (= Tac peptide). Immunoprecipitation experiments with lysates of purified CGL basophils and CD25 MoAbs showed a protein with a molecular weight of 60 Kd, equivalent to the Tac peptide on human T blasts. Quantitative binding studies and Scatchard plot analysis using radiolabeled recombinant human (rh) IL-2 indicated the presence of 12,000 +/- 4,700 low affinity IL-2 binding sites (kd = 66 nmol/L) per purified CGL basophil. Northern blot analysis with enriched CGL basophils showed two messenger RNA bands of 3.5 and 1.5 kilobases hybridizing to radiolabeled Tac cDNA. Immunoprecipitation of the Tac peptide from enriched basophils metabolically labeled with 35S-methionine showed active synthesis of the IL-2 receptor. Our results show that human blood basophils synthesize and express receptors for IL-2.
 ...
PMID:Human blood basophils synthesize interleukin-2 binding sites. 169 35

Five opioid peptides (alpha-, beta-, and gamma-endorphin, methionine- and leucine-enkephalin) were tested for their effect on the concanavalin A-induced proliferative response of splenocytes of adult male F344 rats. The continuous presence of these opioid peptides during culture of T cells did not affect proliferation. However, 30 min of preincubation with beta-endorphin (beta-end), but not with the other opioid peptides, resulted in a dose-dependent enhancement of proliferation of 50-100%. This potentiating effect of beta-end on proliferation was preceded by an increase in the production of interleukin-2 (IL-2) and in the extent of IL-2 receptor expression. The stimulatory effect of beta-end was not prevented by naloxone, indicating that classical opioid receptors were not involved. The continuous presence of beta-end (or alpha-end) in cultures of cells that had been preincubated with beta-end completely abolished the stimulatory effect, pointing towards the potential of beta-end to regulate T-cell function via different mechanisms.
 ...
PMID:Two opposing modes of action of beta-endorphin on lymphocyte function. 203 14

We have made visible the binding of a mouse monoclonal anti-human interleukin 2 (IL-2) receptor (anti-Tac) antibody on the surface of phytohemagglutinin (PHA)-stimulated Xenopus thymocytes using a colloidal gold-conjugated goat anti-mouse antibody and transmission electron microscopy. No binding was found when a different mouse monoclonal antibody (mAb) of the same isotype and subclass was tested, or when the anti-Tac antibody was omitted from the procedure. After metabolic radiolabeling of the IL-2 receptors with [35S]methionine using PHA-stimulated thymocytes of Xenopus laevis, the South African clawed toad, we show that a concentrated preparation of the mouse anti-human Tac antibody will immunoprecipitate a radiolabeled molecule just slightly larger than 55 kDa. Phorbol dibutyrate (PDB), an effective T cell mitogen, and cyclosporin A, an inhibitor of T cell mitogenesis in this species, are both capable of regulating the expression of this IL-2-binding molecule on Xenopus immunocytes. Here, we use the calcium ionophore A23187 to show that the relationship between IL-2 receptor expression and mitogenesis, which was previously established in X. laevis, is associated with a calcium ion flux. Flow cytometry is used for assaying alterations in epitope expression after binding the lectin-stimulated cells under test with a fluorescence (Fl*) conjugate of the anti-Tac antibody or a control mAb, which is either anti-DNP or anti-keyhole limpet hemocyanin (KLH) in specificity, but of the same mouse isotype and subclass as the anti-IL-2 receptor antibody.
 ...
PMID:A monoclonal mouse anti-human IL-2 receptor antibody (anti-Tac) will recognize molecules on the surface of Xenopus laevis immunocytes which specifically bind rIL-2 and are only slightly larger than the human Tac protein. 235 64

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.
 ...
PMID:A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. 240 92

The present study was performed to localize in the IL-2 molecule the active site responsible for interaction with the IL-2 receptor. To predict the receptor binding site on the IL-2 molecule, a computer programme based on the hypothesis that the active site will contain parts of the protein molecule having a high tendency to form a bend was utilized. The tendency to form a bend was evaluated by assessing the probability of beta-turn occurrence; the highest probability was found in the tetrapeptide Asn-Pro-Lys-Leu, occupying the positions 33-36 of the IL-2 molecule. Accordingly, the hexadecapeptide H-Cys-Nle-Gly-Ile-Asn-Asn-Tyr-Lys-Asn-Pro-Lys-Leu-Thr-Arg-Met-Leu-NH2 that spans over the predicted tetrapeptide Asn-Pro-Lys-Leu and comprises the region 27-40 from the IL-2 amino acid sequence was synthesized. This synthetic (I-16) peptide was found to selectively inhibit the IL-2-dependent uptake of 3H-TDR by CTLL cells, apparently by competing with IL-2 for the IL-2 receptor. The synthetic I-16 hexadecapeptide was conjugated to carrier (BSA) protein and used for immunization of rabbits. Resulting I-16 antibodies were capable of binding specifically to the I-16 hexadecapeptide in indirect ELISA test; they reacted substantially with IL-2-producing but not with IL-2-non-producing Jurkat cells in indirect cell membrane immunofluorescence, and inhibited activation of killer spleen cells with human recombinant IL-2 as detected by 51Cr microcytotoxicity assay. Taken together, these results suggest that at least one of the receptor contact sites of the IL-2 is localized within the N-terminal part of the molecule in the region defined by amino acids 27-40 and coded for by the exon 1 and 2.
 ...
PMID:Localization of a receptor binding site on the IL-2 molecule. 244 71

Suppressor T-cell hybridomas specific for the synthetic polypeptide antigen L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) release TsF spontaneously and are not dependent on exogenous sources of lymphokines for their growth. IL-2 has no effect on the cell growth of these hybridomas and little overall effect is observed on protein biosynthesis. Nevertheless, the addition of IL-2 to one of these hybridomas (762 B3.7), leads to a substantial increase in suppressor factor (TsF2) production as measured by both bioactivity and direct analysis of 35S-methionine incorporation into TsF2. Treatment of the TsF2 producing hybridoma with phorbol myristate acetate (PMA) causes an increase in the level of IL-2 receptor expression in this hybridoma and enhances the effects of IL-2 on the biosynthesis of TsF2. These data suggest that in addition to its growth promoting properties, IL-2 may provide a signal that triggers suppressor cells to produce antigen specific suppressor factors.
 ...
PMID:Effect of IL-2 on suppressor factor production. 246 10

A monoclonal antibody, AT-1, is shown to precipitate a p60-65 molecule identical to the Tac antigen. With AT-1, the expression of IL-2 receptors by normal activated human B cells from peripheral blood and tonsils is documented by biosynthetic and immunofluorescence studies. AT-1 precipitated a p60-65 protein from [35S]methionine-labeled activated B cells, similar to that from activated T cells. The interleukin 2 (IL-2) receptor appeared shortly after activation with anti-IgM and B cell-stimulatory factor(s). Its expression reached its peak at 60-72 h with approximately 50% of the B blasts stained by AT-1. Other modes of activation of B cells, by T cell-independent, formalin-treated staphylococci and Epstein-Barr virus, and by T cell-dependent pokeweed mitogen, also induced IL-2 receptor expression. The functional significance of this finding was investigated using recombinant IL-2 (rIL-2). While rIL-2 did not induce resting B cells to proliferate in the presence of anti-IgM, it induced activated B cells to proliferate in the absence of other factors. On the other hand, rIL-2 did not induce the differentiation of these activated B lymphocytes. These data suggest that IL-2 may play a significant role in B cell activation.
 ...
PMID:Detection and functional studies of p60-65 (Tac antigen) on activated human B cells. 609 12

A soluble domain of the interleukin(IL)-2 receptor, the alpha chain synthesized in Escherichia coli, was employed to study expression and refolding of the protein. The results showed that it is possible to obtain biologically active synthetic methionine-free IL-2 receptor alpha chain (synIL-2R alpha) after BrCN cleavage and renaturation of the crude cleavage material, although the alpha chain is expressed as a deglycosylated, methionine-free protein. The soluble receptor comprises amino acids 1-219 and forms 5 disulfide bonds in its biologically active state. Biological activity has been analysed by affinity chromatography and ELISA with mutant [Ala125]IL-2 and monoclonal antibodies as ligands. Renaturation yield is limited mainly by the high aggregation rate of incorrectly folded protein. Aggregation could be limited by varying the oxidation conditions. The deletion of a non-bridging cysteine at position 192 in the synIL-2R alpha did not affect the renaturation yield of the receptor protein. Additionally a cysteine-free and methionine-free beta-galactosidase derivative was fused to the soluble synIL-2R alpha derivatives to prevent reoxidation of incorrect disulfide bonds in the crude BrCN-cleavage material. It is suggested that cysteine impurities from cyanogen-bromide-cleaved peptides might interfere seriously with the refolding process of the synthetic IL-2 receptor alpha-subunit.
 ...
PMID:Isolation and refolding of a mutant methionine-free interleukin-2-receptor alpha chain synthesized as a fusion protein in Escherichia coli. 803 3

The genes encoding the alpha- and beta-chains of the human interleukin-2 receptor were expressed in lepidopteran insect cells using the baculovirus expression vector system. The corresponding genes were inserted under the polyhedrin promoter of the Autographa california nuclear polyhedrosis virus and expressed in the Spodoptera frugiperda insect cell line during viral infection. The recombinant receptor proteins were identified in the insect cell lysates by using protein dot blot and ELISA techniques. At 36 h post infection the corresponding proteins were clearly detected using anti-IL-2 alpha- and beta-receptor-specific antibodies. A large amount of the alpha-chain was also found in the supernatant culture media at 72 h post infection and metabolic labelling with [35S]-methionine indicated that it was proteolytically cleaved into a 32 kDa soluble form. A similar soluble or secreted form of the beta-chain was, however, not observed. Both receptor proteins were expressed on the surface of the insect cells as determined by flow cytometry analysis. Studies performed with the different IL-2 receptor forms (alpha- and beta-chains alone or in combination) in the presence or absence of rIL-2 suggest that the receptor proteins when expressed in infected insect cells are non-functional with respect to tyrosine phosphorylation.
 ...
PMID:Expression of human IL-2 receptor alpha- and beta-chains using the baculovirus expression system. 835 2


1 2 Next >>