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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously established a monoclonal antibody, TU11 mAb, which is specific for human IL-2 receptor (IL-2R) beta chain (p75) and does not inhibit IL-2-binding to IL-2R beta. Using TU11 mAb, we first demonstrated the existence of a third component, p64, of IL-2R, tentatively named the gamma chain of IL-2R. TU11 mAb precipitated not only the beta chain but also the alpha and gamma chains in the lysates of cells bearing the high-affinity IL-2R in the presence of IL-2 without any chemical crosslinker. The gamma chain was also detected in lymphoid MOLT alpha beta and MOLT beta cells, which were stably transfected with both alpha and beta cDNA, and with beta cDNA alone, respectively, but not in fibroblastoid COS alpha beta and COS beta cells, which were stably transfected with both alpha and beta cDNA, and with beta cDNA alone, respectively. Furthermore, IL-2-mediated growth signals were transduced in the lymphoid transfectant cells but not in the fibroblastoid transfectant cells, suggesting the possibility that the gamma chain along with the beta chain has an essential role in the transduction of IL-2-mediated growth signals. Using TU11 mAb, we secondly demonstrated that IL-2 rapidly induces tyrosine phosphorylation of both the beta and gamma chains in an IL-2-dose-dependent manner. The tyrosine phosphorylation of beta and gamma chains were also detected in the lymphoid transfectant cells but not in the fibroblastoid transfectant cells, indicating the correlation between tyrosine kinase activation and IL-2-mediated growth signaling. The beta chain was phosphorylated in in vitro on serine, threonine and tyrosine residues, but the gamma chain was phosphorylated in in vitro predominantly on tyrosine residues, suggesting the possibility that the gamma chain itself is a tyrosine kinase molecule.
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PMID:IL-2-induced signal transduction: involvement of tyrosine kinase and IL-2 receptor gamma chain. 209 Aug 80

We recently isolated a cDNA clone encoding the murine erythropoietin (Epo) receptor from a PXM expression library made from uninduced murine erythroleukemia cells. The clone was identified by screening COS cell transfectants for internalization of radiolabeled recombinant human Epo. As inferred from the cDNA sequence, the murine Epo receptor (Epo-R) is a 507 amino acid polypeptide with a single membrane-spanning domain. Extensive homology was found between the Epo-R and the interleukin 2 receptor beta chain, both at the level of amino acid sequence and at the level of regional hydrophobicity.
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PMID:Erythropoietin receptor: cloning strategy and structural features. 215 75

Interleukin 4 (IL-4) is a potent mediator of growth and differentiation for various lymphoid and myeloid cells. To isolate a cDNA encoding the murine IL-4 receptor, we have developed an expression cloning method that uses biotinylated ligand as a probe and that may be generally applicable to cloning of receptor genes. COS-7 cells transiently transfected with the cloned full-length cDNA bind murine IL-4 specifically with a Kd = 165 pM. Crosslinking of 125I-labeled IL-4 to COS-7 cells transfected with the cDNA reveals binding to proteins of 120-140 kDa. IL-4-responsive cells also express IL-4-binding proteins of 120-140 kDa but show additional bands at 60-70 kDa; the relationship of the smaller proteins to the larger ones is unclear. The nucleotide sequence indicates that the full-length cDNA encodes 810 amino acids including the signal sequence. While no consensus sequence for protein kinases is present in the cytoplasmic domain, a sequence comparison with the erythropoietin receptor, the IL-6 receptor, and the beta chain of the IL-2 receptor reveals a significant homology in the extracellular domain, indicating that the IL-4 receptor is a member of a cytokine receptor family.
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PMID:Expression cloning of a cDNA encoding the murine interleukin 4 receptor based on ligand binding. 240 98

We have cloned cDNA encoding the mouse interleukin-2 (IL-2) receptor from a murine T cell line, CTLL using human IL-2 receptor cDNA as probe. COS 7 cells transfected with the cDNA expressed the antigen recognized by the monoclonal antibody against the murine IL-2 receptor. The cDNA identified 4 species of mRNA (4.5, 3.5, 2.2 and 1.5 kb) of the mouse IL-2 receptor in CTLL cells. Difference in the length of mRNA seems to be ascribed to the variable length of the 3' untranslated sequence. Total nucleotide sequence (approximately 1400 bp) of this cDNA was determined and compared with the human receptor. The nucleotide and amino acid sequences of the IL-2 receptor are 70% and 60%, respectively, homologous in average between the two species. The comparison has revealed several conserved regions localized to particular exons such as transmembrane and cytoplasmic portions, suggesting that these regions are important for receptor function and its regulation.
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PMID:Nucleotide sequence of mouse IL-2 receptor cDNA and its comparison with the human IL-2 receptor sequence. 298 26

Complementary DNAs corresponding to the human receptor for interleukin 2 (IL-2) have been molecularly cloned, sequenced, and expressed in COS-1 cells. The human genome appears to contain a single structural gene for this receptor; however, when transcribed at least two messenger RNAs (mRNAs) are produced which vary in length due to the use of different polyadenylation signals. Sequence analysis of the cloned complementary DNAs indicates an alternate pathway of mRNA processing for this receptor. Splicing of a 216 base pairs segment contained within the protein coding region results in an mRNA unable to code for the IL-2 receptor. In contact complementary DNAs corresponding to unspliced mRNA encode membrane receptors which bind both IL-2 and anti-Tac (monoclonal anti-IL-2 receptor antibody). Analysis of the deduced amino acid sequence reveals that the receptor is composed of 272 amino acids including a signal peptide 21 amino acids in length. Hydrophobicity analysis suggests a single 19 amino acid transmembrane domain. A short intracytoplasmic domain composed of 13 amino acids is present at the carboxy terminus and contains three potential phosphate acceptor sites (serine and threonine but not tyrosine) and typical positively charged amino acids presumably involved in cytoplasmic anchoring. Two sites for N-linked glycosylation sites and numerous extracytoplasmic O-linked glycosylation sites are present.
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PMID:Isolation and expression of complementary DNAs encoding the human interleukin 2 receptor. 299 Jun 88

Complementary DNAs corresponding to the human receptor for interleukin-2 (IL-2) have been molecularly cloned, sequenced, and expressed in both COS-1 and L cells. The human genome appears to contain a single structural gene for this receptor located on the short arm of chromosome 10 (band 14-15). However, when transcribed, at least two families of mRNAs are produced, which vary in length due to the use of at least three different polyadenylation signals. Sequence analysis of the cloned cDNAs and S1 nuclease protection assays indicate an alternative pathway of mRNA processing for this receptor whereby a 216 base-pair segment contained within the protein coding region is spliced, resulting in an mRNA unable to encode a functional IL-2 receptor. In contrast, cDNAs corresponding to mRNA retaining this 216 base-pair region code membrane receptors that bind both IL-2 and anti-Tac (monoclonal anti-IL-2 receptor antibody). Analysis of the deduced amino acid sequence reveals that the receptor is composed of 272 amino acids including a signal peptide 21 amino acids in length. Hydrophobicity analysis suggests a single, 19 amino acid transmembrane domain. A short intracytoplasmic domain composed of 13 amino acids is present and contains two potential phosphate acceptor sites (serine and threonine but not tyrosine) as well as positively charged residues presumably involved in cytoplasmic anchoring. Two sites for N-linked glycosylation sites and numerous extracytoplasmic O-linked glycosylation sites are present.
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PMID:The human interleukin-2 receptor. 393 83

The human interleukin-2 (IL-2) receptor was purified by affinity chromatography using the anti-Tac monoclonal antibody, and its N-terminal amino acid sequence was determined. Complementary DNA clones were isolated and sequenced to reveal the primary structure of the IL-2 receptor precursor, which has 272 amino acid residues. The receptor is separated into two domains by a putative 19-residue transmembrane region. Two mRNAs (1.4 and 3.5 kilobases) hybridizing to the cDNA clone were found in human T cells bearing the IL-2 receptor. The cDNA directed synthesis of the IL-2 receptor in COS cells.
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PMID:Molecular cloning of cDNA encoding human interleukin-2 receptor. 609 Sep 49

T lymphocytes, essential for the generation of a normal immune response, require the presence of the lymphokine interleukin-2 (IL-2) in order to proliferate. Cells that respond to IL-2 possess a surface receptor glycoprotein specific for this lymphokine. We have recently purified and chemically characterized the IL-2 receptor from both phytohaemagglutinin-activated human T cells and the human T-cell lymphoma HUT-102 (ref. 5). From the NH2-terminal protein sequence obtained in that study, we have now used synthetic oligonucleotides to probe a complementary DNA library, prepared from HUT-102 messenger RNA, for the presence of cDNA clones that might code for the IL-2 receptor. Two cDNA clones were isolated which had closely related DNA sequences. Interestingly, only one coded for an active receptor when transfected into COS-7 cells. This clone contained a 216-base pair (bp) insert that was not present in the other clone. The insert was flanked by an 8-bp direct repeat reminiscent of a transposable element, and appeared to code for a region of marked structural homology to the NH2-terminal region of the receptor molecule.
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PMID:Cloning, sequence and expression of human interleukin-2 receptor. 609 20

The interleukin (IL)-2 receptor system has previously been shown to signal through the association and tyrosine phosphorylation of Shc. This study demonstrates that the IL-2 receptor beta (IL-2R beta) chain is the critical receptor component required to mediate this effect. The use of IL-2R beta chain deletion mutants transfected into a Ba/F3 murine cell model describes a requirement for the IL-2R beta "acid-rich" domain between amino acids 315 and 384 for Shc tyrosine phosphorylation and receptor association. COS cell co-transfection studies of IL-2R beta chain constructs containing point mutations of tyrosine to phenylalanine along with the tyrosine kinase Jak-1 and a hemagglutinin-tagged Shc revealed that the motif surrounding phosphorylated tyrosine 338 within the acid-rich domain of the IL-2R beta is a binding site for Shc. Deletion of this domain has previously been shown to abrogate the ability of IL-2 to activate Ras but does not affect IL-2-dependent mitogenesis in the presence of serum. Proliferation assays of Ba/F3 cells containing IL-2R beta chain deletion mutants in serum-free medium with or without insulin shows that deletion of the acid-rich domain does not affect IL-2-driven mitogenesis regardless of the culture conditions. This study thus defines the critical domain within the IL-2R beta chain required to mediate Shc binding and Shc tyrosine phosphorylation and further shows that Shc binding and phosphorylation are not required for IL-2-dependent mitogenesis. Neither serum nor insulin is required to supplement the loss of induction of the Shc adapter or Ras pathways, which therefore suggests a novel mechanism for mitogenic signal transduction mediated by this hematopoietin receptor.
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PMID:Analysis of interleukin-2-dependent signal transduction through the Shc/Grb2 adapter pathway. Interleukin-2-dependent mitogenesis does not require Shc phosphorylation or receptor association. 749 11

X-linked severe combined immunodeficiency (XSCID) is characterized by absent or profoundly reduced numbers of T cells and normal numbers of B cells in the circulation. Affected patients have mutations of the interleukin-2 (IL-2) receptor gamma chain gene. Using Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) established from two unrelated XSCID patients, we could show that neither expressed the IL-2 receptor gamma chain on the cell surface. A novel cytokine IL-15, which has biologic activities similar to those of IL-2, could bind to the XSCID B-LCLs in the absence of the gamma chain, although both the beta and gamma chains of the human IL-2 receptor were previously shown to be required for IL-15 binding by transfected COS cells. Furthermore, a significant reduction and delay of IL-15 internalization by B lymphoblasts from XSCID patients was observed when compared with that of normal control B-LCLs. These results show the existence of a novel IL-15-specific receptor component that contributes to IL-15 binding but is insufficient for IL-15 internalization in the absence of the IL-2 receptor gamma chain.
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PMID:Characterization of B-cell lines established from two X-linked severe combined immunodeficiency patients: interleukin-15 binds to the B cells but is not internalized efficiently. 763 50


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