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)

A continuous cloned cell line (Y479) was established by culturing normal mouse spleen cells in a high concentration of interleukin-2 (IL-2). Y479 cells showed morphological characteristics of large granular lymphocyte with the phenotypes of Thy-1.2+, T3+, Lyt-1-, Lyt-2-, L3T4-, B220-, AsGM1+, LFA-1+, and TcRV beta 8-. The Y479 cells required a high concentration of IL-2 for their growth but did not express detectable p55 IL-2 receptor (IL-2R) although they bound IL-2 with high and low affinities. Analysis of the IL-2 binding proteins on the Y479 cells revealed that both the high and low affinity receptors consisted only of 70 kDa protein. Analysis of the 70 kDa protein was performed using five monoclonal antibodies (L15, L20, L23, L34, and L61) against human recombinant IL-2. Although they recognized different epitopes, all monoclonal antibodies immunoprecipitated 70 kDa IL-2R that was cross-linked with radioiodinated IL-2. The supernatant after immunoprecipitation with L61 still contained IL-2/IL-2R complex that was L23-reactive, and the supernatant after immunoprecipitation with L23 contained L61-reactive IL-2/IL-2R complex, whereas L15 immunoprecipitated almost all the complex. Limited digestion of IL-2-cross-linked Y479 cells with trypsin caused the liberation of 45 kDa IL-2R fragment cross-linked with IL-2. This complex was immunoprecipitated by L15 or L61 but not by L23. These results suggest that there are at least two distinct 70 kDa IL-2R on the surface of Y479 cells.
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PMID:Two distinct P70 interleukin-2 receptors on a murine large granular lymphocyte clone Y479. 179 Oct 35

Products prepared from broth extracts of beta-hemolytic Group A streptococci activate human natural killer (NK) cells. The active moiety is likely a protein since the enhancing capability is destroyed by the proteolytic enzyme pronase, although not by trypsin. The enhancement in NK cytotoxicity is due at least in part to lymphokines, since normal peripheral blood mononuclear cells and T cells, upon incubation with streptococcal products (SP), release supernatant factors which augment NK activity. These cell culture supernatants contain interferons (IFN) as well as low levels of interleukin-2 (IL-2). Treatment of supernatants with anti-IFN antibodies has variable effects, depending on the donor cells used to produce the factors. In most cases, anti-IFN-gamma totally abrogates enhancement. Treatment of supernatants with antibodies to IFN-alpha modestly decreases enhancement of most donor cells; however, IFN-alpha appears not to be a major factor in SP-activated lymphokines. Pretreating effector cells with a monoclonal antibody directed against the IL-2 receptor (anti-Tac) usually reduces the supernatant effect. The combination of anti-Tac and anti-IFN-gamma totally nullifies enhancement. Thus T lymphocytes stimulated with streptococcal products augment NK activity at least in part by producing IFN-gamma and a factor whose activity is reduced by the interaction of the IL-2 receptor with anti-Tac.
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PMID:The mechanism of enhancement of natural killer cell activity by soluble streptococcal products. 242 53

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.
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PMID:Evidence for two extracellular domains in the human interleukin-2 receptor: localization of IL-2 binding. 310 28

Human lymphocytes respond to IL-2 with the generation of MHC-unrestricted oncolytic activity. This function has been named lymphokine-activated killing (LAK). To investigate the mechanism by which IL-2 activates and maintains LAK, we have examined the role(s) of IL-2 cell surface receptors. Removal or blockade of unstimulated lymphocytes expressing the IL-2 receptor Tac does not preclude the acquisition of LAK function. Therefore, a non-Tac IL-2 receptor was proposed to be involved in LAK generation. Using direct 125I-IL-2 binding to Tac-negative LAK precursors suggested the existence of such an alternate IL-2 receptor. Chemical crosslinking of 125I-IL-2 to Tac-depleted lymphocytes followed by SDS-PAGE determined that the size of the non-Tac-binding protein was approximately 75 kDa. Tac-negative lymphocytes activated by a limited IL-2 pulse which was insufficient for detectable Tac upregulation indicated that an initial non-Tac pathway was involved in functional differentiation. The development of lytic function, Tac upregulation, and cellular proliferation was prohibited by trypsin, a treatment shown also to eliminate 125I-IL-2 binding to Tac-negative lymphocytes. The Tac antigen, although not involved in the initial generation of LAK, is involved in the proliferative maintenance of this lytic function.
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PMID:Functional differentiation of human lymphokine-activated killing (LAK) is distinct from expansion and involves dissimilar interleukin 2 receptors. 312 71

In the IL-2-dependent murine cytotoxic T cell line CTLL-2, IL-2 induced a rapid and transient decrease in Co(2+)-trypsin-treated activity of protein phosphatase PP1. The PP1 activity declined to a minimum level, being 70% of control value, in 20 min after the addition of IL-2 but recovered to the control level within 45 min. The decrease of PP1 activity was dependent on IL-2 concentration and occurred specifically in cytosolic fraction. Similar alteration was observed in IL-2 sensitive murine T-lymphoblasts. Neither activity of protein phosphatase PP2A nor PP2C showed alteration during the IL-2 stimulation. These results suggest that PP1 plays an important role in early events of the intracellular growth signaling from the IL-2 receptor.
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PMID:IL-2 induces transient and specific decrease in cytosolic protein phosphatase PP1 activity in murine T cell lines. 839 34

Mast cells (MCs) originate from multipotent hematopoietic progenitor cells. However, MCs in various organs are heterogenous in terms of mediator or receptor expression and response to diverse stimuli. We characterized the phenotype and functional properties of human renal mast cells (HRMCs). Tissue was obtained from 17 patients suffering from renal tumors (transitional cell carcinoma, n = 4; renal cell carcinoma, n = 13). HRMCs were isolated by collagenase digestion. Double staining with toluidine blue and immunofluorescence using monoclonal antibodies (mAbs) revealed expression of stem cell factor (SCF)-receptor (c-kit/CD117), CD9, CD29, CD33, CD43, CD44, CD54, and CD63 on HRMCs. In contrast, HRMCs were not recognized by mAbs to CD2, CD3, CD4, CD11b, CD14, CD15, CD16, CDw17, CD19, or CD23. HRMCs were also negative for CD116 (granulocyte-macrophage colony-stimulating factor [GM-CSF] receptor alpha), CD123 (interleukin [IL]-3Ralpha), CD121a (IL-1R type I), CD122 (IL-2Rbeta), and CD127 (IL-7R) and were also found to lack C5aR (CD88). Ligand-induced activation of HRMCs through immunoglobulin (Ig)E-R or SCF-R (c-kit) resulted in histamine secretion (control: <10%; alphaIgE, 1 microg/mL: 50.12 +/-5.18%; rhSCF, 100 ng/mL: 29.24 +/- 22.39), whereas recombinant C5a, erythropoietin (EPO), IL-1 through 10, and GM-CSF exerted no effects. As determined by in situ staining, HRMCs contained tryptase, but only low or undetectable amounts of chymase. Electron microscopy confirmed the presence of MCs in renal tissues and revealed a scroll-rich granule population in HRMCs. Together, HRMCs are tryptase+, C5aR- mast cells exhibiting phenotypic and functional properties similar to those of lung MCs.
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PMID:Phenotypic and functional characterization of mast cells derived from renal tumor tissues. 947 5