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)

The expression of the interleukin-2 (IL-2) receptor was studied in neoplastic cells derived from acute leukemias, T-cell lymphoblastic lymphomas, peripheral T-cell lymphomas, chronic lymphocytic leukemias, well-differentiated lymphocytic lymphomas, and established cell lines by both flow cytometric analysis and sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) after affinity crosslinking of radiolabeled IL-2. Cells from most acute leukemias (19 of 22), irrespective of their subtype (T, common or nonlymphoid leukemias), as well as T-cell lymphoblastic lymphomas and peripheral T-cell lymphomas expressed only the p70-75 beta subunit of the IL-2 receptor. Cells from the more mature B-cell neoplasms, chronic lymphocytic leukemia, and well-differentiated lymphocytic lymphoma, expressed predominantly alpha beta IL-2 receptors (11 of 14). In contrast to these results, most cell lines established from hematopoietic malignancies do not express either chain of the IL-2 receptor. Further studies are necessary to determine the exact function of the IL-2R p70-75 beta subunit in immature hematopoietic cells, but its wide distribution throughout the hematopoietic system suggests that IL-2 may play a role in the early stages of hematopoiesis.
 ...
PMID:Expression of interleukin-2 receptor beta subunit in hematopoietic malignancies. 265 67

Interleukin 2 (IL-2) receptor expression was examined on recombinant IL-2 (rIL-2)-propagated tumor-infiltrating lymphocytes (TIL) from eight metastatic melanoma and three sarcoma samples. All 11 TIL expanded with similar growth rates. rIL-2 propagated TIL from five of eight metastatic melanoma specimens contained no Tac antigen-positive lymphocytes as determined by immunofluorescence and flow cytometry performed multiple times during the 4 to 8 week culture period. However, "Tac-negative" TIL did express the non-Tac IL-2-binding peptide, p70-75 as determined by [125I]IL-2 cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IL-2-binding assays revealed that these "Tac-negative" TIL expressed only an intermediate affinity IL-2 receptor. In contrast, TIL from the other three of eight melanoma and all three sarcoma contained one-third Tac-positive cells as assessed by flow cytometry analysis, and expressed surface non-Tac (p70-75) and Tac (p55) peptides by [125I]IL-2 cross-linking. These "Tac-positive" TIL displayed both the high and intermediate affinity IL-2 receptors. However, rIL-2-dependent growth of both "Tac-negative" and "Tac-positive" TIL was significantly inhibited by anti-Tac mAb, suggesting a transient Tac expression on the "Tac-negative" TIL. Additionally, due to the limits of our methodology, we cannot rule out the possibility of a constitutive expression of a low level of Tac, with an indicible expression of higher levels. Addition of culture supernatants from phytohemagglutinin- and phorbol myristate acetate-stimulated peripheral blood mononuclear cells to the "Tac-negative" TIL-induced detectable Tac expression within 48 h. These results indicate that both non-Tac and Tac IL-2 receptors play important roles during IL-2-dependent proliferation of TIL.
 ...
PMID:Involvement of both Tac and non-Tac interleukin 2-binding peptides in the interleukin 2-dependent proliferation of human tumor-infiltrating lymphocytes. 278 85

Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA.
 ...
PMID:Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. 278 15

To compare in vitro and in vivo cyclosporin A (CyA) effects on early events involved in human T cell activation, lymphocytes obtained from healthy donors and from diabetic patients undergoing CyA therapy were studied for their interleukin 2 (IL-2) responsiveness, surface IL-2 receptor (IL-2R) expression and IL-2R mRNA accumulation, following stimulation with mitogen or anti-CD3 monoclonal antibody. T cells recovered from eight in vivo CyA-treated patients and stimulated in vitro for 4 h with mitogen or anti-CD3 (in the absence of CyA) showed significant (50-60%) inhibition of Tac mRNA accumulation, as assessed and quantified by scanning densitometry. Conversely, these cells showed no modification in their expression of membrane alpha (p55, Tac) or beta (p70) chains of IL-2R in binding experiments performed with both iodinated anti-Tac and IL-2 following 18 h stimulation with either mitogen or anti-CD3. Normal lymphocytes treated in vitro with CyA showed significant inhibition of alpha chain IL-2R expression both at the mRNA and the membrane level. At variance, expression of the IL-2R beta chain was unaffected; a significant number of high-affinity IL-2 binding sites was still detectable after in vitro CyA treatment. These results suggest that: (1) a residual immunosuppressive effect of CyA on T cell activation may be evidenced in in vivo treated cells by measuring very early events triggered following short-term stimulation; (2) CyA activity on T cell activation seems similar in vivo and in vitro; and (3) the described approach would be potentially useful to monitor the individual in vivo immunosuppressive capacity of CyA.
 ...
PMID:In vitro and in vivo action of cyclosporin A on the induction of human interleukin-2 receptor alpha and beta chains. 278 15

Human lymphotropic virus, HTLV-1, encodes in its proviral genome a transcriptional activator protein, tax-1, that may be responsible for the development of virus-induced adult T cell leukemia (ATL), possibly through the aberrant activation of the genes for interleukin-2 (IL-2) and one of its receptor (IL-2R) components, the IL-2 receptor alpha-chain (IL-2R alpha). In the present study, an expression plasmid containing tax-1 cDNA under the control of HTLV-1 LTR was introduced into mouse and human CD4-positive T cell lines. Analysis of the established cell clones revealed a number of interesting features: (i) a limited fraction of the total cell population (less than 25% in each clone) was positive for IL-2R alpha; (ii) the IL-2R alpha expression was not permanent, as the IL-2R alpha positive and negative cells could convert either way. The experimental data suggest that the observed heterogeneity in IL-2R alpha expression in the transformants is due to a cell-cycle-regulated expression and function of tax-1. Furthermore, a proportion of the induced IL-2R in EL-4 was in high-affinity form, suggesting the association of the IL-2R alpha and the IL-2R beta chain (p70-75) components.
 ...
PMID:Transient induction of IL-2 receptor in cultured T cell lines by HTLV-1 LTR-linked tax-1 gene. 279 77

It is well-known that the most prominent age-related immunological abnormalities were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigens. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample. The sixth, the combined stimulation with PMA and ionomycin could induce proliferative response to highly purified T cells, T cell subsets and B cells. The degree of age-related decline of the proliferative response of CD-8 positive T cells was most significant, that of CD-4 positive ones was next and that of B cells was least. The seventh, although the maximum of c-myc mRNA level was attained at 2 hr after the stimulation and similar amount between the both age groups, the amount of mRNA at 8 or 24 hr was rather higher in the aged T cells than in the young ones. The reduction of the degradation rate of c-myc mRNA seemed to be the cause. We found no difference of the maximum amount and kinetics of c-myb mRNA between both age groups in T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[The characteristic changes of immune function with aging]. 281 Oct 4

In this report, we examined whether novel interleukin 2 (IL-2) binding molecules (p70/75) are responsible for signal transduction and internalization of IL-2 in T cells by using a monoclonal antibody H-31 to Tac antigens. We found that H-31 inhibited the binding of IL-2 to Tac antigens but not novel IL-2 binding molecules. Scatchard plot analysis revealed that in the presence of H-31, intermediate affinity sites (Kd = 1 to 1.5 nM) were detectable and the number of them was similar to that of high affinity IL-2 receptor (IL-2R) (Kd = 10 to 15 pM) in the absence of H-31. Furthermore, the kinetics of endocytosis of IL-2 via p70/75 showed the same pattern as via high affinity IL-2R. Finally, high doses of IL-2 (100 to 10,000 U/ml) are required for the proliferation of T cells in the presence of H-31, whereas in the absence of H-31, physiologic doses of IL-2 (1 to 100 U/ml) induced the proliferation. These results taken together suggest that novel IL-2 binding molecules are related to signal transduction of IL-2 and that Tac antigens are essential for constructing of high affinity IL-2R, although Tac antigens may not be responsible for signal transduction.
 ...
PMID:Interleukin 2 functions through novel interleukin 2 binding molecules in T cells. 282 93

Interleukin-2 (IL-2) binds to both high- and low-affinity classes of IL-2 receptors on activated T lymphocytes. Only the high-affinity receptors are involved in receptor-mediated endocytosis and normally transduce the mitogenic signals of IL-2; however, the structural features distinguishing the high- and low-affinity receptors are unknown. When 125I-labeled IL-2 was chemically cross-linked to activated human T lymphocytes, two major bands were identified. First, as predicted, a 68- to 72-kilodalton band, consisting of IL-2 (15.5 kilodaltons) cross-linked to the IL-2 receptor (55 kilodaltons), was observed. Second, an unpredicted 85- to 92-kilodalton moiety was detected. This band was not present when IL-2 was cross-linked to transfected C127 cells, which exclusively express low-affinity receptors. The data presented are most consistent with the existence of a 70- to 77-kilodalton glycoprotein subunit (p70) which, upon associating with the 55-kilodalton low-affinity receptor (p55), transforms it into a high-affinity site. It is proposed that p55 and p70 be referred to as the alpha and beta subunits, respectively, of the high-affinity IL-2 receptor.
 ...
PMID:Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. 309 22

Although activated human T and B lymphocytes express both high-affinity and low-affinity membrane receptors for interleukin-2 (IL-2), the structural features that distinguish these receptors have remained unresolved. The high-affinity receptors appear to mediate IL-2 induced T cell growth and internalization of IL-2, whereas no function has yet been ascribed to the low-affinity receptors. The Tac antigen is an IL-2 binding protein of relative molecular mass 55,000 (Mr 55K) that participates in the formation of both high- and low-affinity receptors. But Tac complementary DNA transfection and membrane fusion studies have suggested that additional T-cell components are required to produce high-affinity IL-2 receptors. In this study, we report the identification of a second human IL-2 binding protein that (1) has an Mr of approximately 70K, (2) lacks reactivity with the anti-Tac antibody, (3) binds IL-2 with intermediate affinity and (4) is present on the surface of resting T cells, large granular lymphocytes (natural killer cells), and certain T and B cell lines in the absence of the Tac antigen. Chemical crosslinking of 125I-labelled IL-2 bound to high-affinity IL-2 receptors produces labelling of both the p70 protein and the Tac antigen and the anti-Tac antibody blocks the crosslink detection of both of these proteins. Expression of Tac cDNA in a T cell line expressing the p70 protein, but lacking both Tac and high-affinity receptors, results in the reconstitution of high-affinity IL-2 receptors in these cells. Together, these findings suggest that the high-affinity human IL-2 receptor may be a membrane complex composed of at least the p70 protein and Tac antigen.
 ...
PMID:A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. 310 74

To elucidate mechanisms underlying neovascularization that accompanies certain chronic immune/inflammatory disorders, the effects of interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) on endothelial cell (EC) growth in vitro and angiogenesis in vivo were studied. Preincubation of cultured human ECs with IFN-alpha, followed by exposure to IL-2, resulted in effective stimulation of cell growth, whereas either cytokine alone had only a slight effect. The combination of IFN-alpha/IL-2 induced an angiogenic response in the rabbit cornea. IL-2 receptor expression was enhanced on IFN-alpha-treated ECs: p55 was increased and p70 was induced. 125I-IL-2 binding to ECs treated with IFN-alpha was enhanced (Kd from approximately 7 nM to approximately 260 pM with IFN-alpha), and anti-p55 IgG blocked 125I-IL-2/EC interaction as well as IL-2-mediated EC proliferation. Consistent with these findings in cell culture, immunohistologic studies demonstrated p55 and p70 antigen in the vasculature of rheumatoid joints, but not in normal joint tissue. Exposure of cultured ECs to IFN-alpha increased levels of intracellular EC basic fibroblast growth factor (bFGF), and subsequent addition of IL-2 led to bFGF release into the medium. The observation that anti-bFGF IgG largely blocked EC proliferation in response to IFN-alpha/IL-2 suggested that bFGF was a critical agent in this setting. These data suggest a mechanism rendering ECs responsive to IL-2 which may be relevant in immune/inflammatory disorders: IFN-alpha-mediated induction of functional EC receptors for IL-2, which drives cell proliferation by a mechanism dependent on increased synthesis and release of bFGF.
 ...
PMID:Interferon-alpha and interleukin 2 synergistically enhance basic fibroblast growth factor synthesis and induce release, promoting endothelial cell growth. 768 71


<< Previous 1 2 3 4 Next >>