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

IL-2 regulates growth and differentiation of various types of cells in the immune system via its interaction with IL-2 receptor (IL-2R). The high and intermediate-affinity IL-2Rs, which consist of the alpha beta gamma heterotrimer complex and the beta gamma heterodimer complex, respectively, harbor the function of the intracellular signal transduction, indicating that the beta and gamma chains are indispensable for the signal transduction but not the alpha chain. The reconstitution studies of IL-2Rs with alpha, beta and gamma chain genes demonstrated that each subunit has potential for altering the affinity of the receptor, and the cytoplasmic domains of the beta and gamma chains participate in signal transduction in terms of cell growth, activation of alpha tyrosine kinase and enhancement of c-myc, c-fos and c-jun transcription. The region containing the SH2 homologous sequence of the gamma chain should have a critical function for signal transduction. On the other hand, common subunits are known to be shared among receptors for IL-3, IL-5 and GM-CSF, and receptors for IL-6, LIF, OSM and LIF. We have demonstrated that the monoclonal antibody specific for the IL-2R gamma chain completely inhibited not only IL-2-dependent cell growth but also IL-4-dependent, IL-7-dependent, and IL-9-dependent cell growth, suggesting that the gamma chain is possibly shared among receptors for IL-2, IL-4, IL-7 and IL-9. Impairment of the gamma chain function is considered to be closely related to human XSCID characterized by profound T cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Structure and function of IL-2 receptor subunits]. 802 15

We have investigated the role of JAK3 in interleukin 2 (IL-2)-induced signal transduction with a human T cell line, ED40515(-), lacking expression of the IL-2 receptor gamma chain and its sublines transfected with wild-type or mutant cDNAs of the IL-2 receptor gamma chain. Our results demonstrated that the membrane-proximal cytoplasmic region, encompassing the src homology region 2 (SH2)-like subdomain, of the gamma chain is essential for association and activation of JAK3. Furthermore, IL-2-induced activation of JAK3 paralleled induction of the c-myc gene and DNA synthesis but not induction of the c-fos and c-jun genes. These results support the hypothesis that JAK3 plays a pivotal role in the IL-2 receptor-mediated signals for cell growth.
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PMID:Interleukin 2-induced activation of JAK3: possible involvement in signal transduction for c-myc induction and cell proliferation. 808 65

Transforming growth factor-beta (TGF beta) is a potent immunosuppressive cytokine which inhibits the antigen (Ag)-dependent expansion of T cells both in vitro and in vivo by mechanisms not well defined yet. Here we report that exposure of interleukin (IL)-2-dependent T cell lines to TGF beta 2 results in apoptosis defined by morphology, nucleosomal size DNA fragmentation and in situ DNA end labeling. TGF beta 2-induced T cell apoptosis showed the following characteristics: (1) in contrast to the rapid evolution of apoptosis following IL-2 deprivation, apoptosis of T cells triggered by TGF beta 2 was delayed; (2) cycloheximide prevented TGF beta 2-induced apoptosis of CTLL-2 but not of OVA-7 T helper cells; (3) in contrast to apoptosis following IL-2 deprivation, TGF beta 2-mediated T cell apoptosis was not associated with decreased expression of the proto-oncogenes, bcl-2 or c-myc; (4) TGF beta 2-induced apoptosis was not restricted to IL-2-dependent T cell lines since the IL-4-dependent T cell line, CT.4S, as well as EL4 lymphoma cells, which grow independently of exogenous IL-2, were also susceptible to TGF beta 2-mediated apoptosis. Taken together, these data may present a novel mechanism of TGF beta 2-mediated suppression of T cell expansion in response to Ag and IL-2, the activation of the endogenous death program of apoptosis, which appears to operate independently of direct interactions of TGF beta 2 with the IL-2/IL-2 receptor system.
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PMID:Transforming growth factor-beta 2 induces apoptosis of murine T cell clones without down-regulating bcl-2 mRNA expression. 820 89

Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src family kinases, tyrosine phosphorylation of several proteins, conversion of Ras to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction. The IL-2R beta chain plays a crucial role in IL-2R signaling. Within the cytoplasmic domain of the beta chain, a region essential for mitogenesis and another involved in binding the Src family kinase Lck have been defined. The beta chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras activation, we examined the role of Shc in IL-2 signaling. Shc was found to be tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its phosphorylation, Shc interacted with another adapter protein, Grb2, and, via Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also associated with the IL-2R beta chain. Thus, during IL-2 signaling, the interaction of Shc with the IL-2R beta chain and its simultaneous association with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling.
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PMID:The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation. 829 3

We isolated a cDNA clone for the gamma chain of the mouse interleukin 2 receptor. Introduction of the mouse gamma chain cDNA clone into a mouse fibroblast cell line, L929, expressing the mouse alpha beta heterodimer IL-2 receptor converted pseudo-high affinity of the IL-2 receptor into functional high, resulting in internalization of IL-2 and induction of the c-myc, c-fos and c-jun genes. The mouse beta gamma heterodimer, however, failed to bind IL-2 unlike the human beta gamma heterodimer intermediate-affinity receptor. These results indicate that the mouse functional IL-2 receptor is a complex comprising three distinct subunits, alpha, beta and gamma chains, but the beta gamma heterodimer is not functional and different from the human heterodimer.
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PMID:Cloning of the mouse interleukin 2 receptor gamma chain: demonstration of functional differences between the mouse and human receptors. 850 26

Mouse MHC class I-specific mAbs recognizing the alpha 1/alpha 2, but not those directed against the alpha 3 domain of the molecule, inhibited RNA, protein, and DNA synthesis of splenic T cells in response to stimulation through the TCR/CD3 complex. Similar inhibition was seen with LFA-1-specific mAbs under the same stimulation conditions. The effect of class I- and LFA-1-specific mAbs reflected a decrease of both IL-2 and IFN-gamma synthesis and IL-2 receptor alpha chain induction. IL-2, IL-2 receptor alpha chain, IFN-gamma, c-fos, c-jun, and c-myc mRNAs were not detected. Activation of AP-1 (c-Fos and c-Jun proteins) and NF-kappa B transcription factors were also inhibited. Inhibition was observed both after treatment of cells in culture and after intravenous injection of Abs in mice. Although bulk phosphorylation was inhibited, early tyrosine phosphorylation and calcium ion influx were normally induced. Protein phosphatase inhibitors did not reverse this inhibition, ruling out an enhanced activation of these enzymes in the observed inhibition. Cell surface expression of one of early PKC activation marker, CD69 was also inhibited. Phorbol esters that directly activate PKC prevented inhibition. Thus, class I molecules are implicated in signal transduction involved at an early stage for T cell activation in a manner that suggests their implication in accessory signal transmission that contributes to the regulation of PKC activity.
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PMID:MHC class I molecules are implicated in costimulatory signals during TCR/CD3-induced activation. 859 31

Interleukin-2 (IL-2) has been shown to stimulate ACTH secretion by anterior pituitary cells and has been implicated in pathophysiological processes of the pituitary and brain in several major neuropsychiatric disorders. The present study tested the hypothesis that IL-2 receptor-beta (IL-2R beta), a constitutively expressed and essential subunit for IL-2 signaling in lymphocytes, is expressed by AtT-20 pituitary cells and involved in transducing intracellular signals induced by IL-2. We isolated and sequenced three overlapping IL-2R beta cDNA clones from AtT-20 pituitary cells representing key regions of the gene protein coding sequence. These cDNA clones including conserved sequences shared by growth hormone and prolactin as well as intracytoplasmic Src and JAK family homology domains of nonreceptor protein tyrosine kinases essential for IL-2 signaling in lymphocytes. Their nucleotide sequences were 100% homologous with those expressed by lymphocytes (together they comprised 70% of the full length coding sequence). The IL-2R beta gene is constitutively expressed by AtT-20 pituitary cells, and its transcription was upregulated after CRF stimulation. Species-specific Il-2 induced intracellular signals in AtT-20 cells known to be mediated by Il-2R beta, including a transient increase in c-myc nuclear proto-oncogene transcription and the dose-dependent induction of DNA replication as measured by [3H]thymidine incorporation. The IL-2-induced DNA replication signal was not delivered by heat inactivated IL-2 and was partially blocked by a murine anti-IL-2R beta monoclonal antibody. These studies suggest that IL-2R beta may be a critical target involved in mediating the neuroimmunological actions of this prototypical cytokine in endocrine cells.
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PMID:Isolation of IL-2 receptor-beta cDNA clones from AtT-20 pituitary cells: constitutive expression and role in signal transduction. 925 80

The expression of various proto-oncogenes in primary culture of lymphocytes from peripheral blood of bovine with chronic lymphocytic leukemia (CLL) was studied. Cellular proto-oncogenes encode proteins that propagate growth, differentiation or apoptosis signals from cell membrane to nucleus. The proliferation and differentiation of normal eukaryotic cells are precisely controlled. Tumor cells usually are characterized both by the continuous growth signal and by the block of cell differentiation. We have previously reported that along with spontaneous proliferation, bovine CLL lymphocytes continuously differentiate and enter apoptosis in vitro. CLL cells with an autocrine growth mechanism and at the same time undergoing spontaneous differentiation and apoptosis in vitro provide a new model system to investigate the possible involvement of various proto-oncogenes in the regulation of cellular proliferation, differentiation and apoptosis. Northern blot analysis revealed simultaneous expression of a number of proto-oncogenes in CLL cells. Transcripts of c-fos, c-myc, c-myb, A-raf, c-raf1, hck, IL-2 receptor alpha-chain (IL-2R alpha) were found in lymphocytes at the peak of their proliferative activity in culture. Kinetics studies demonstrated that CLL cells constitutively express transcripts of so-called immediate response nuclear proto-oncogenes c-myc, c-fos as well as cytoplasmic proto-oncogenes hck and c-raf1, i.e., genes coding for tyrosine and serine-threonine protein kinases, respectively. Expression level did not change significantly during all stages of CLL cells in culture. The results show that continuous expression of c-myc mRNA does not prevent CLL cell differentiation and may be associated with apoptotic cell death.
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PMID:Proto-oncogene expression in bovine peripheral blood leukemic lymphocytes during their spontaneous proliferation, differentiation and apoptosis in vitro. 959 70

Interleukin 2 (IL-2)- and IL-4-mediated stimulation of survival and growth, reflected by the induction of bcl2 and c-myc, respectively, depends on the integrity of the membrane-proximal region (S-region) in the IL-2 receptor beta-chain (IL-2R beta) and the haematopoietin homology box1-containing region of the IL-4 receptor alpha-chain (IL-4R alpha). In contrast to IL-4, IL-2 induces the expression of c-fos and c-jun family genes, mediated by the acidic region (A-region) within the cytoplasmic domain of IL-2R beta. A highly acidic motif is also present in IL-4R alpha, and evidence in favour and against its importance has been published. The authors have constructed chimeric receptors between IL-2R beta and IL-4R alpha by substitution of either the S-region or the A-region of IL-2R beta with sequences derived from IL-4R alpha. These chimeras were stably transfected into BA/F3 cells and assayed for the capacity to restore functions of IL-2 beta, such as growth mediation by IL-2 and the induction of proto-oncogenes (c-myc, c-junB and c-fos). Replacement of both the S- and A-region of IL-2R beta with IL-4R alpha derived regions of similar size and cytoplasmic location supported growth-stimulation by IL-2 as well as proto-oncogene induction. In contrast, all IL-2R functions were lost by exchange of the S-region with the corresponding part of IL-4R alpha. Induction of c-junB and c-fos RNA as an indicator of A-region function, however, was maintained in an IL-2R beta chimera containing the acidic box-bearing region of IL-4R alpha. These data indicate a functional role of the acidic region in the IL-4R alpha-chain.
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PMID:Function of the human interleukin 4 receptor (IL-4R)-derived acidic motif revealed by cytoplasmic domain chimeras of the IL-4R alpha chain and the IL-2R beta chain. 961 70

In this review we discuss several molecules that are attractive candidates as transducing molecules involved in signaling processes. IL-2 receptor signaling is a complex process involving a large number of molecules: Ras, Rho, PI3 kinase, PKC, Akt, transcription factors NF-AT, and NF-kappaB and some target genes such as bcl-2, c-myc, c-jun and c-fos. Ras and Rho have been defined as dual molecules because Ras- and Rho-initiated signals can either promote or inhibit apoptosis. Several studies have contributed to the delineation of a signaling pathway structured in three independent channels designated channels 1, 2, and 3. These three channels serve as major landmarks: Lck-c-fos/c-jun (channel 1), Syk-myc (channel 2), and a pathway leading to actin organization/bcl-2 expression (channel 3). The detailed hierarchical organization of these three channels is presented throughout the review and the model is depicted in the figure.
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PMID:IL-2-induced cellular events. 963 10


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