The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Warren J Leonard - One of the best experts on this subject based on the ideXlab platform.
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both integrated and differential regulation of components of the il 2 il 2 Receptor system
Cytokine & Growth Factor Reviews, 2006Co-Authors: Hyoungpyo Kim, Jean Imbert, Warren J LeonardAbstract:Abstract Interleukin-2 was discovered in 1976 as a T-cell growth factor. It was the first type I cytokine cloned and the first for which a Receptor component was cloned. Its importance includes its multiple actions, therapeutic potential, and lessons for Receptor biology, with three components differentially combining to form high, intermediate, and low-affinity Receptors. IL-2Rα and IL-2Rβ, respectively, are markers for double-negative thymocytes and regulatory T-cells versus memory cells. γ c , which is shared by six cytokines, is mutated in patients with X-linked severe-combined immunodeficiency. We now cover an under-reviewed area—the regulation of genes encoding IL-2 and IL-2R components, with an effort to integrate/explain this knowledge.
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an indirect effect of stat5a in il 2 induced proliferation a critical role for stat5a in il 2 mediated il 2 Receptor α chain induction
Immunity, 1997Co-Authors: Hiroshi Nakajima, Anthony Wynshawboris, Louis A Rosenthal, Kazunori Imada, David S Finbloom, Lothar Hennighausen, Warren J LeonardAbstract:Abstract Stat5a was identified as a prolactin-induced transcription factor but also is activated by other cytokines, including interleukin-2 (IL-2) and IL-7. We have now analyzed the immune system of Stat5a-deficient mice. Stat5a −/− splenocytes exhibited defective IL-2–induced expression of the IL-2 Receptor α chain (IL-2Rα), a protein that together with IL-2Rβ and the common cytokine Receptor γ chain (γ c ) mediates high-affinity IL-2 binding. Correspondingly, Stat5a −/− splenocytes exhibited markedly decreased proliferation to IL-2, although maximal proliferation was still achieved at IL-2 concentrations high enough to titrate intermediate-affinity IL-2Rβ/γ c Receptors. Thus, defective Stat5a expression results in diminished proliferation by an indirect mechanism, resulting from defective Receptor expression. Correspondingly, we show that Stat5a is essential for maximal responsiveness to antigenic stimuli in vivo, underscoring the physiological importance of IL-2–induced IL-2Rα expression.
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an il 2 response element in the human il 2 Receptor alpha chain promoter is a composite element that binds stat5 elf 1 hmg i y and a gata family protein
The EMBO Journal, 1996Co-Authors: Susan John, C M Robbins, Warren J LeonardAbstract:Abstract Expression of the human interleukin-2 (IL-2) Receptor alpha chain gene is potently upregulated by its own ligand, IL-2. In this study, we characterize an essential upstream IL-2 response element that contains both consensus and non-consensus GAS motifs, two putative Ets binding sites (EBS), one of which overlaps the consensus GAS motif, and a GATA motif, which overlaps the non-consensus GAS motif. We demonstrate that although the individual components of this element do not respond to IL-2, together they form a composite element capable of conferring IL-2 responsiveness to a heterologous promoter. Multiple factors including Stat5, Elf-1, HMG-I(Y) and GATA family proteins bind to the IL-2 response element and mutation of any one of these binding sites diminishes the activity of this element. An unidentified Ets family protein binds to the EBS overlapping the consensus GAS motif and appears to negatively regulate the human IL-2R alpha promoter. Thus, IL-2-induced IL-2R alpha promoter activity requires a complex upstream element, which appears to contain binding sites for both positive and negative regulatory factors.
Thomas A Waldmann - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Multichain Interleukin-2 Receptor: A Target for Immunotherapy in Lymphoma
2016Co-Authors: Thomas A WaldmannAbstract:Activation of resting T cells induces synthesis of interleukin-2 (IL-2) and expression of its specific high-affinity recep-tor. We proposed a multichain model for the high-affinity IL-2 Receptor in which both a 55-kilodalton IL-2-binding peptide identified by the anti-Tac monoclonal antibody and a 70/75-kilodalton IL-2-binding peptide are associated in a Receptor complex. The IL-2 Receptor is proving to be an extraordinarily versatile therapeutic target, since it is expressed by the abnormal T cells in patients with cer-tain lymphoid malignancies or autoimmune disorders and in individuals rejecting allografts, whereas it is not ex-pressed by normal resting cells. Monoclonal antibodies and toxin-lymphokine conjugates directed toward IL-2 Receptors represent novel therapeutic agents for these clinical condi-tions. [J Natl Cancer Inst 81:914-923, 1989
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daclizumab anti tac zenapax in the treatment of leukemia lymphoma
Oncogene, 2007Co-Authors: Thomas A WaldmannAbstract:Daclizumab (Zenapax) identifies the alpha subunit of the interleukin-2 (IL-2) Receptor and blocks the interaction of this cytokine with its growth factor Receptor. The scientific basis for the choice of the IL-2 Receptor alpha subunit as a target for monoclonal antibody-mediated therapy of leukemia/lymphoma is that very few normal cells express IL-2R alpha, whereas the abnormal T cells in patients with an array of lymphoid malignancies express this Receptor. In 1997, daclizumab was approved by the FDA for use in the prevention of renal allograft rejection. In addition, anti-Tac provided effective therapy for select patients with T-cell malignancies and an array of inflammatory autoimmune disorders. Finally, therapy with this antibody armed with (90)Y has led to clinical responses in the majority of patients with adult T-cell leukemia. These insights concerning the IL-2/IL-2 Receptor system facilitated the development of effective daclizumab antibody therapy for select patients with leukemia/lymphoma.
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Anti-Tac (daclizumab, Zenapax) in the Treatment of Leukemia, Autoimmune Diseases, and in the Prevention of Allograft Rejection: A 25-Year Personal Odyssey
Journal of Clinical Immunology, 2007Co-Authors: Thomas A WaldmannAbstract:Twenty-five years ago, we reported the production of the monoclonal antibody, anti-Tac that identifies the IL-2 Receptor alpha subunit and blocks the interaction of IL-2 with this growth factor Receptor. In 1997, daclizumab (Zenapax^®), the humanized form of this antibody, was approved by the FDA for use in the prevention of renal allograft rejection. In addition, we demonstrated that daclizumab is of value in the treatment of patients with noninfectious uveitis, multiple sclerosis, and the neurological disease human T-cell lymphotropic virus I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Others demonstrated therapeutic efficacy with daclizumab in patients with pure red cell aplasia, aplastic anemia, and psoriasis. Thus, translation of basic insights concerning the IL-2/IL-2 Receptor system obtained using the monoclonal antibody daclizumab provided a useful strategy for the prevention of organ allograft rejection and the treatment of patients with select autoimmune diseases or T-cell leukemia/lymphoma.
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treatment of noninfectious intermediate and posterior uveitis with the humanized anti tac mab a phase i ii clinical trial
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Robert B Nussenblatt, Pushpa Sran, Eric Fortin, Rhett M Schiffman, Luiz V Rizzo, Janine Smith, Paul Van Veldhuisen, Anita Yaffe, Carolyn K Goldman, Thomas A WaldmannAbstract:To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 Receptor mAb (Daclizumab) therapy in the treatment of patients with severe, sight-threatening, intermediate and posterior noninfectious uveitis, a nonrandomized, open-label, pilot study was performed. Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 Receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. All patients were able to tolerate the study medications without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2 Receptor therapy may be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile.
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recruitment of sh2 containing protein tyrosine phosphatase shp 1 to the interleukin 2 Receptor loss of shp 1 expression in human t lymphotropic virus type i transformed t cells
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Thisau Migone, Thomas A Waldmann, Nicholas A Cacalano, Naomi Taylor, James A JohnstonAbstract:Interleukin 2 (IL-2) rapidly induces tyrosine phosphorylation of intracellular substrates, including the IL-2 Receptor β chain (IL-2Rβ), Janus kinase 1 (Jak1), Jak3, signal transducer/activator of transcription proteins, and Shc, but the mechanism underlying dephosphorylation of these proteins is not known. The src homology 2 (SH2) containing tyrosine phosphatase 1 (SHP-1) is recruited by several hematopoietic surface Receptors indicating that this phosphatase plays an important role as a regulator of signaling. We have found that IL-2 induces association of SHP-1 with the IL-2 Receptor complex, and that once SHP-1 is recruited to the activated Receptor it is able to decrease tyrosine phosphorylation of IL-2Rβ and the associated tyrosine kinases Jak1 and Jak3. This dephosphorylation is specific as expression of a catalytically inactive form of SHP-1, or expression of the related phosphatase SHP-2 did not result in dephosphorylation of the IL-2 Receptor components. Furthermore, we have found that SHP-1 expression is greatly decreased or undetectable in a number of IL-2 independent HTLV-I transformed T cell lines that exhibit constitutive Jak/signal transducer/activator of transcription activation. In HTLV-I infected T cells, down-regulation of SHP-1 expression was also found to correlate with the acquisition of IL-2 independence. These observations suggest that SHP-1 normally functions to antagonize the IL-2 signal transduction pathway and that HTLV-I infection and oncogenic transformation can lead to loss of SHP-1 expression resulting in constitutive activation of IL-2 regulated T cell responses.
Tadatsugu Taniguchi - One of the best experts on this subject based on the ideXlab platform.
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protein tyrosine kinase syk is associated with and activated by the il 2 Receptor possible link with the c myc induction pathway
Immunity, 1995Co-Authors: Yasuhiro Minami, Atsuo Kawahara, Yoko Nakagawa, Tadaski Miyazaki, Kiyonao Sada, Hirohei Yamamura, Tadatsugu TaniguchiAbstract:Abstract The IL-2 Receptor (IL-2R) consists of three subunits, the IL-2Rα, IL-2Rβ, and IL-2Rγ chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2Rβ and IL-2Rγ, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) Is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2Rβ chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c- myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.
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the il 2 il 2 Receptor system a current overview
Cell, 1993Co-Authors: Tadatsugu Taniguchi, Yasuhiro MinamiAbstract:Tadatsugu Taniguchi and Yasuhiro Mlnami Institute for Molecular and Cellular Biology Osaka University Yamadaoka 1-3, Suita-shi Osaka 565 Japan The discovery and molecular characterization of interleu- kin-2 (IL-2) has had a considerable impact on basic and clinical immunology(Morgan et al., 1976; Taniguchi et al., 1963; Rosenberg et al., 1965). The IL-2 system has been extensively studied in the context of the clonal proliferation of T cells and has become a paradigm of how interleukins and other soluble mediators, collectively termed cyto- kines, function in the development and regulation of the immune system. The proliferation of matured, resting T cells is initiated via signal transduction, in which the spe- cific interaction of the antigen-major histocompatibility complex molecule with the Tcell antigen Receptor complex (TCR) induces the expression of IL-2 and its homologous Receptor. In effect, this IL-2-induced cell proliferative re- sponse is a key determinant affecting the magnitude of the immune response. IL-2 is also known to function in other lymphoid cell types, including thymocytes and B cells, as well as in some nonlymphoid cells (reviewed in Smith, 1964; Greene and Leonard, 1966; Shimizu et al., 1966; Waldmann, 1969; Minami et al., 1993a). More re- cently, it has been reported that IL-2 also programs T cells to undergo apoptosis following TCR stimulation (Lenardo, 1991). The IL-2 Receptor is unique among growth factor recep- tors in that it is made up of at least three distinct membrane components: the a chain (IL-2Ra), the 6 chain (IL-PR6), and the y chain (IL-PRY). The genes encoding these com- ponents have been cloned and characterized. Expression of the genes encoding IL-2Ra and the IL-2 ligand are unde- tectable in resting T cells but are efficiently induced upon T cell activation. The IL-2Rj3 gene is expressed constitu- tively in CD6’ cytotoxic T cells but not in CD4+ helper T cells; the IL-2R3 gene is further induced upon T cell activation, whereas IL9RT is expressed constitutively in lymphoid cells (see reviews; Takeshita et al., 1992). IL9R6 and IL-PRY, but not IL-2Ra, belong to a newly identified superfamily of cytokine Receptors, characterized by four conserved cysteines and the sequence WSXWS (the WS motif) (Figure 1). In humans, expression of differ- ent combinations of these three components gives rise to the generation of various forms of the IL-2 Receptor, each of which manifests different binding affinities to IL-2. As shown in Table 1, the combination of the 6 and y chains is required for signal transduction, but reconstitution of the high affinity (Kd = 10-l’ M) form of the IL-2 Receptor requires the additional participation of the
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the il 2 Receptor complex its structure function and target genes
Annual Review of Immunology, 1993Co-Authors: Yasuhiro Minami, Takeshi Kono, Tadaaki Miyazaki, Tadatsugu TaniguchiAbstract:: Proliferation of T lymphocytes is triggered by the interaction of IL-2 with its specific Receptor following T lymphocyte activation. The Receptor for IL-2 consists of at least three distinct subunits, the alpha chain (IL-2R alpha), the beta chain (IL-2R beta), and the gamma chain (IL-2R gamma). Although the role of IL-2R gamma in IL-2 signalling remains unclear, IL-2R beta is the subunit critical for Receptor-mediated signalling. Because IL-2R beta lacks any apparent catalytic motifs, IL-2R beta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2R beta have revealed that at least two distinct cytoplasmic regions of IL-2R beta are involved in IL-2-induced cellular signalling. The "serine-rich" region of IL-2R beta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2R beta mutant cDNAs lacking a particular cytoplasmic region or regions were expressed in an IL-3-dependent mouse pro-B cell line (BAF-B03). Meanwhile, another cytoplasmic region of IL-2R beta, the "acidic" region, is responsible for its physical association with an src-family protein tyrosine kinase (PTK), p56lck and is critical for activating the p56lck PTK following IL-2 stimulation. It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction. One pathway is linked to tyrosine phosphorylation events, mediated by a src-family protein tyrosine kinase (PTK), and that pathway leads to the induction of the c-fos, c-jun, and other genes of this family. Another pathway leads to c-myc gene induction by an as yet unknown mechanism. We discuss the complex signalling machinery that links the cell surface Receptor to the nuclear events.
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interaction of the il 2 Receptor with the src family kinase p56lck identification of novel intermolecular association
Science, 1991Co-Authors: Masanori Hatakeyama, Takeshi Kono, Naoki Kobayashi, Atsuo Kawahara, Steven D Levin, Roger M Perlmutter, Tadatsugu TaniguchiAbstract:In the interleukin-2 (IL-2) system, intracellular signal transduction is triggered by the beta chain of the IL-2 Receptor (IL-2R beta); however, the responsible signaling mechanism remains unidentified. Evidence for the formation of a stable complex of IL-2R beta and the lymphocyte-specific protein tyrosine kinase p56lck is presented. Specific association sites were identified in the tyrosine kinase catalytic domain of p56lck and in the cytoplasmic domain of IL-2R beta. As a result of interaction, IL-2R beta became phosphorylated in vitro by p56lck. Treatment of T lymphocytes with IL-2 promotes p56lck kinase activity. These data suggest the participation of p56lck as a critical signaling molecule downstream of IL-2R via a novel interaction.
Yasuhiro Minami - One of the best experts on this subject based on the ideXlab platform.
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protein tyrosine kinase syk is associated with and activated by the il 2 Receptor possible link with the c myc induction pathway
Immunity, 1995Co-Authors: Yasuhiro Minami, Atsuo Kawahara, Yoko Nakagawa, Tadaski Miyazaki, Kiyonao Sada, Hirohei Yamamura, Tadatsugu TaniguchiAbstract:Abstract The IL-2 Receptor (IL-2R) consists of three subunits, the IL-2Rα, IL-2Rβ, and IL-2Rγ chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2Rβ and IL-2Rγ, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) Is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2Rβ chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c- myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.
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the il 2 il 2 Receptor system a current overview
Cell, 1993Co-Authors: Tadatsugu Taniguchi, Yasuhiro MinamiAbstract:Tadatsugu Taniguchi and Yasuhiro Mlnami Institute for Molecular and Cellular Biology Osaka University Yamadaoka 1-3, Suita-shi Osaka 565 Japan The discovery and molecular characterization of interleu- kin-2 (IL-2) has had a considerable impact on basic and clinical immunology(Morgan et al., 1976; Taniguchi et al., 1963; Rosenberg et al., 1965). The IL-2 system has been extensively studied in the context of the clonal proliferation of T cells and has become a paradigm of how interleukins and other soluble mediators, collectively termed cyto- kines, function in the development and regulation of the immune system. The proliferation of matured, resting T cells is initiated via signal transduction, in which the spe- cific interaction of the antigen-major histocompatibility complex molecule with the Tcell antigen Receptor complex (TCR) induces the expression of IL-2 and its homologous Receptor. In effect, this IL-2-induced cell proliferative re- sponse is a key determinant affecting the magnitude of the immune response. IL-2 is also known to function in other lymphoid cell types, including thymocytes and B cells, as well as in some nonlymphoid cells (reviewed in Smith, 1964; Greene and Leonard, 1966; Shimizu et al., 1966; Waldmann, 1969; Minami et al., 1993a). More re- cently, it has been reported that IL-2 also programs T cells to undergo apoptosis following TCR stimulation (Lenardo, 1991). The IL-2 Receptor is unique among growth factor recep- tors in that it is made up of at least three distinct membrane components: the a chain (IL-2Ra), the 6 chain (IL-PR6), and the y chain (IL-PRY). The genes encoding these com- ponents have been cloned and characterized. Expression of the genes encoding IL-2Ra and the IL-2 ligand are unde- tectable in resting T cells but are efficiently induced upon T cell activation. The IL-2Rj3 gene is expressed constitu- tively in CD6’ cytotoxic T cells but not in CD4+ helper T cells; the IL-2R3 gene is further induced upon T cell activation, whereas IL9RT is expressed constitutively in lymphoid cells (see reviews; Takeshita et al., 1992). IL9R6 and IL-PRY, but not IL-2Ra, belong to a newly identified superfamily of cytokine Receptors, characterized by four conserved cysteines and the sequence WSXWS (the WS motif) (Figure 1). In humans, expression of differ- ent combinations of these three components gives rise to the generation of various forms of the IL-2 Receptor, each of which manifests different binding affinities to IL-2. As shown in Table 1, the combination of the 6 and y chains is required for signal transduction, but reconstitution of the high affinity (Kd = 10-l’ M) form of the IL-2 Receptor requires the additional participation of the
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the il 2 Receptor complex its structure function and target genes
Annual Review of Immunology, 1993Co-Authors: Yasuhiro Minami, Takeshi Kono, Tadaaki Miyazaki, Tadatsugu TaniguchiAbstract:: Proliferation of T lymphocytes is triggered by the interaction of IL-2 with its specific Receptor following T lymphocyte activation. The Receptor for IL-2 consists of at least three distinct subunits, the alpha chain (IL-2R alpha), the beta chain (IL-2R beta), and the gamma chain (IL-2R gamma). Although the role of IL-2R gamma in IL-2 signalling remains unclear, IL-2R beta is the subunit critical for Receptor-mediated signalling. Because IL-2R beta lacks any apparent catalytic motifs, IL-2R beta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2R beta have revealed that at least two distinct cytoplasmic regions of IL-2R beta are involved in IL-2-induced cellular signalling. The "serine-rich" region of IL-2R beta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2R beta mutant cDNAs lacking a particular cytoplasmic region or regions were expressed in an IL-3-dependent mouse pro-B cell line (BAF-B03). Meanwhile, another cytoplasmic region of IL-2R beta, the "acidic" region, is responsible for its physical association with an src-family protein tyrosine kinase (PTK), p56lck and is critical for activating the p56lck PTK following IL-2 stimulation. It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction. One pathway is linked to tyrosine phosphorylation events, mediated by a src-family protein tyrosine kinase (PTK), and that pathway leads to the induction of the c-fos, c-jun, and other genes of this family. Another pathway leads to c-myc gene induction by an as yet unknown mechanism. We discuss the complex signalling machinery that links the cell surface Receptor to the nuclear events.
Toshikazu Takeshita - One of the best experts on this subject based on the ideXlab platform.
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the interleukin 2 Receptor gamma chain its role in the multiple cytokine Receptor complexes and t cell development in xscid
Annual Review of Immunology, 1996Co-Authors: Kazuo Sugamura, Motonari Kondo, Naoto Ishii, Masataka Nakamura, Hironobu Asao, Nobuyuki Tanaka, Kazuyuki Ohbo, Toshikazu TakeshitaAbstract:Interleukin 2 (IL-2), a T cell-derived cytokine, targets a variety of cells to induce their growth, differentiation, and functional activation. IL-2 inserts signals into the cells through IL-2 Receptors expressed on cell surfaces to induce such actions. In humans, the functional IL-2 Receptor consists of the subunit complexes of the alpha, beta and gamma chains, or the beta and gamma chains. The third component, the gamma chain, of IL-2 Receptor plays a pivotal role in formation of the full-fledged IL-2 Receptor, together with the beta chain, the gamma chain participates in increasing the IL-2 binding affinity and intracellular signal transduction. Moreover, the cytokine Receptors for at least IL-2, IL-4, IL-7, IL-9, and IL-15 utilize the same gamma chain as an essential subunit. Interestingly, mutations of the gamma chain gene cause human X-linked severe combined immunodeficiency (XSCID) characterized by a complete or profound T cell defect. Among the cytokines sharing the gamma chain, at least IL-7 is essentially involved in early T cell development in the mouse organ culture system. The molecular identification of the gamma chain brought a grasp of the structures and functions of the cytokine Receptor and an in-depth understanding of the cause of human XSCID. To investigate the mechanism of XSCID and development of gene therapy for XSCID, knockout mice for the gamma chain gene were produced that showed similar but not exactly the same phenotypes as human XSCID.
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sharing of the interleukin 2 il 2 Receptor gamma chain between Receptors for il 2 and il 4
Science, 1993Co-Authors: Motonari Kondo, Toshikazu Takeshita, Naoto Ishii, Masataka Nakamura, Sumiko Watanabe, Kenichi Arai, Kazuo SugamuraAbstract:The gamma chain of the interleukin-2 (IL-2) Receptor is an indispensable subunit for IL-2 binding and intracellular signal transduction. A monoclonal antibody to the gamma chain, TUGm2, inhibited IL-2 binding to the functional IL-2 Receptors and also inhibited IL-4-induced cell growth and the high-affinity binding of IL-4 to the CTLL-2 mouse T cell line. Another monoclonal antibody, TUGm3, which reacted with the gamma chain cross-linked with IL-2, also immunoprecipitated the gamma chain when cross-linked with IL-4. These results suggest that the IL-2 Receptor gamma chain is functionally involved in the IL-4 Receptor complex.
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cloning of the gamma chain of the human il 2 Receptor
Science, 1992Co-Authors: Toshikazu Takeshita, Satoru Kumaki, Naoto Ishii, Masataka Nakamura, Hironobu Asao, Kiyoshi Ohtani, Nobuyuki Tanaka, Hiroshi Munakata, Kazuo SugamuraAbstract:A third subunit, the gamma chain, of the human interleukin-2 Receptor (IL-2R) was identified, and a complementary DNA clone encoding this member of the cytokine Receptor family was isolated. The gamma chain is necessary for the formation of the high- and intermediate-affinity Receptors, which consists of alpha beta gamma heterotrimers and beta gamma heterodimers, respectively. The IL-2R on murine fibroblastoid cells can be internalized after binding IL-2 only if the gamma chain is present; alpha and beta are insufficient for internalization. Thus, the gamma chain is an indispensable component of the functional IL-2R.
