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CUTTING EDGE |
-Chain Is an Indispensable Subunit of the IL-21 Receptor Complex1
*
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan;
Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan;
Department of Functional Cloning, ZymoGenetics, Seattle, WA 98102; and
Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation, Tokyo, Japan
The common 
-chain (c) is an
indispensable subunit of the functional receptor complexes for IL-4,
IL-7, IL-9, and IL-15 as well as IL-2. Here we show that the
c is also shared with the IL-21R complex. Although IL-21
binds to the IL-21R expressed on c-deficient
ED40515- cells, IL-21 is unable to transduce any
intracytoplasmic signals. However, in ED-16 cells, a
c-transfected ED40515- cell line, IL-21
binds to the IL-21R and can activate Janus kinase (JAK)1, JAK3, STAT1,
and STAT3. The chemical cross-linking study reveals the direct binding
of IL-21 to the c. These data clearly demonstrate that
the c is an indispensable subunit of the functional
IL-21R complex.
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A. Ozawa, H. Tada, R. Tamai, A. Uehara, K. Watanabe, T. Yamaguchi, H. Shimauchi, H. Takada, and S. Sugawara Expression of IL-2 receptor {beta} and {gamma} chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2 J. Leukoc. Biol., September 1, 2003; 74(3): 352 - 359. [Abstract] [Full Text] [PDF]
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J. A. Toomey, F. Gays, D. Foster, and C. G. Brooks Cytokine requirements for the growth and development of mouse NK cells in vitro J. Leukoc. Biol., August 1, 2003; 74(2): 233 - 242. [Abstract] [Full Text] [PDF]
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H.-L. Ma, M. J. Whitters, R. F. Konz, M. Senices, D. A. Young, M. J. Grusby, M. Collins, and K. Dunussi-Joannopoulos IL-21 Activates Both Innate and Adaptive Immunity to Generate Potent Antitumor Responses that Require Perforin but Are Independent of IFN-{gamma} J. Immunol., July 15, 2003; 171(2): 608 - 615. [Abstract] [Full Text] [PDF]
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M. Aringer, S. R. Hofmann, D. M. Frucht, M. Chen, M. Centola, A. Morinobu, R. Visconti, D. L. Kastner, J. S. Smolen, and J. J. O'Shea Characterization and Analysis of the Proximal Janus Kinase 3 Promoter J. Immunol., June 15, 2003; 170(12): 6057 - 6064. [Abstract] [Full Text] [PDF]
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M. Strengell, S. Matikainen, J. Siren, A. Lehtonen, D. Foster, I. Julkunen, and T. Sareneva IL-21 in Synergy with IL-15 or IL-18 Enhances IFN-{gamma} Production in Human NK and T Cells J. Immunol., June 1, 2003; 170(11): 5464 - 5469. [Abstract] [Full Text] [PDF]
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H. Hackstein, T. Taner, A. F. Zahorchak, A. E. Morelli, A. J. Logar, A. Gessner, and A. W. Thomson Rapamycin inhibits IL-4--induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo Blood, June 1, 2003; 101(11): 4457 - 4463. [Abstract] [Full Text] [PDF]
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D. S. Mehta, A. L. Wurster, M. J. Whitters, D. A. Young, M. Collins, and M. J. Grusby IL-21 Induces the Apoptosis of Resting and Activated Primary B Cells J. Immunol., April 15, 2003; 170(8): 4111 - 4118. [Abstract] [Full Text] [PDF]
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J. Giron-Michel, M. Fogli, A. Gaggero, S. Ferrini, A. Caignard, D. Brouty-Boye, S. Baouz, M.-C. Le Bousse-Kerdiles, B. Peault, M. van Dijk, et al. Detection of a Functional Hybrid Receptor {gamma}c/GM-CSFR{beta} in Human Hematopoietic CD34+ Cells J. Exp. Med., March 17, 2003; 197(6): 763 - 775. [Abstract] [Full Text] [PDF]
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F. Bennett, D. Luxenberg, V. Ling, I-M. Wang, K. Marquette, D. Lowe, N. Khan, G. Veldman, K. A. Jacobs, V. E. Valge-Archer, et al. Program Death-1 Engagement Upon TCR Activation Has Distinct Effects on Costimulation and Cytokine-Driven Proliferation: Attenuation of ICOS, IL-4, and IL-21, But Not CD28, IL-7, and IL-15 Responses J. Immunol., January 15, 2003; 170(2): 711 - 718. [Abstract] [Full Text] [PDF]
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A. Suto, H. Nakajima, K. Hirose, K. Suzuki, S.-i. Kagami, Y. Seto, A. Hoshimoto, Y. Saito, D. C. Foster, and I. Iwamoto Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cepsilon transcription of IL-4-stimulated B cells Blood, December 15, 2002; 100(13): 4565 - 4573. [Abstract] [Full Text] [PDF]
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 K. Ozaki, R. Spolski, C. G. Feng, C.-F. Qi, J. Cheng, A. Sher, H. C. Morse III, C. Liu, P. L. Schwartzberg, and W. J. Leonard A Critical Role for IL-21 in Regulating Immunoglobulin Production Science, November 22, 2002; 298(5598): 1630 - 1634. [Abstract] [Full Text] [PDF]
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M. A. Cooper, J. E. Bush, T. A. Fehniger, J. B. VanDeusen, R. E. Waite, Y. Liu, H. L. Aguila, and M. A. Caligiuri In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells Blood, November 15, 2002; 100(10): 3633 - 3638. [Abstract] [Full Text] [PDF]
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J. Parrish-Novak, D. C. Foster, R. D. Holly, and C. H. Clegg Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses J. Leukoc. Biol., November 1, 2002; 72(5): 856 - 863. [Abstract] [Full Text] [PDF]
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M. Minagawa, H. Watanabe, C. Miyaji, K. Tomiyama, H. Shimura, A. Ito, M. Ito, J. Domen, I. L. Weissman, and K. Kawai Enforced Expression of Bcl-2 Restores the Number of NK Cells, But Does Not Rescue the Impaired Development of NKT Cells or Intraepithelial Lymphocytes, in IL-2/IL-15 Receptor {beta}-Chain-Deficient Mice J. Immunol., October 15, 2002; 169(8): 4153 - 4160. [Abstract] [Full Text] [PDF]
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A. L. Wurster, V. L. Rodgers, A. R. Satoskar, M. J. Whitters, D. A. Young, M. Collins, and M. J. Grusby Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon {gamma}-producing Th1 Cells J. Exp. Med., October 7, 2002; 196(7): 969 - 977. [Abstract] [Full Text] [PDF]
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M. Strengell, T. Sareneva, D. Foster, I. Julkunen, and S. Matikainen IL-21 Up-Regulates the Expression of Genes Associated with Innate Immunity and Th1 Response J. Immunol., October 1, 2002; 169(7): 3600 - 3605. [Abstract] [Full Text] [PDF]
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 P J Felsburg Overview of immune system development in the dog: comparison with humans Human and Experimental Toxicology, September 1, 2002; 21(9-10): 487 - 492. [Abstract] [PDF]
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E. J. Tsai, H. L. Malech, M. R. Kirby, A. P. Hsu, N. E. Seidel, C. D. Porada, E. D. Zanjani, D. M. Bodine, and J. M. Puck Retroviral transduction of IL2RG into CD34+ cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras Blood, June 17, 2002; 100(1): 72 - 79. [Abstract] [Full Text] [PDF]
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A.-T. Brenne, T. Baade Ro, A. Waage, A. Sundan, M. Borset, and H. Hjorth-Hansen Interleukin-21 is a growth and survival factor for human myeloma cells Blood, May 15, 2002; 99(10): 3756 - 3762. [Abstract] [Full Text] [PDF]
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T. J. Fry and C. L. Mackall Interleukin-7: from bench to clinic Blood, May 13, 2002; 99(11): 3892 - 3904. [Full Text] [PDF]
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G. Demirci, W. Gao, X. X. Zheng, T. R. Malek, T. B. Strom, and X. C. Li On CD28/CD40 Ligand Costimulation, Common {gamma}-Chain Signals, and the Alloimmune Response J. Immunol., May 1, 2002; 168(9): 4382 - 4390. [Abstract] [Full Text] [PDF]
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F. Olosz and T. R. Malek Structural Basis for Binding Multiple Ligands by the Common Cytokine Receptor gamma -Chain J. Biol. Chem., March 29, 2002; 277(14): 12047 - 12052. [Abstract] [Full Text] [PDF]
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 T. Licht, M. Haskins, P. Henthorn, S. E. Kleiman, D. M. Bodine, T. Whitwam, J. M. Puck, M. M. Gottesman, and J. R. Melniczek Drug selection with paclitaxel restores expression of linked IL-2 receptor gamma -chain and multidrug resistance (MDR1) transgenes in canine bone marrow PNAS, February 20, 2002; (2002) 52712199. [Abstract] [Full Text] [PDF]
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L. A. Myers, D. D. Patel, J. M. Puck, and R. H. Buckley Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival Blood, February 1, 2002; 99(3): 872 - 878. [Abstract] [Full Text] [PDF]
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T. Licht, M. Haskins, P. Henthorn, S. E. Kleiman, D. M. Bodine, T. Whitwam, J. M. Puck, M. M. Gottesman, and J. R. Melniczek Drug selection with paclitaxel restores expression of linked IL-2 receptor gamma -chain and multidrug resistance (MDR1) transgenes in canine bone marrow PNAS, March 5, 2002; 99(5): 3123 - 3128. [Abstract] [Full Text] [PDF]
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