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Science 11 November 1994:
Vol. 266. no. 5187, pp. 1042 - 1045
DOI: 10.1126/science.7973658
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Articles

Science, Vol 266, Issue 5187, 1042-1045
Copyright © 1994 by American Association for the Advancement of Science

articles

Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID

SM Russell, JA Johnston, M Noguchi, M Kawamura, CM Bacon, M Friedmann, M Berg, DW McVicar, BA Witthuhn, O Silvennoinen, and al. et

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.


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   Abstract »    PDF »
Toxicologic Pathology of Cytokines, Cytokine Receptors, and Other Recombinant Human Proteins: Development of a Recombinant Interleukin-4-Pseudomonas Exotoxin for Therapy of Glioblastoma.
R. K. Puri (1999)
Toxicol Pathol 27, 53-57
   Abstract »    PDF »
Interleukin 7 Receptor Control of  T Cell Receptor gamma  Gene Rearrangement: Role of Receptor-associated Chains and Locus Accessibility.
S. K. Durum, S. Candeias, H. Nakajima, W. J. Leonard, A. M. Baird, L. J. Berg, and K. Muegge (1998)
J. Exp. Med. 188, 2233-2241
   Abstract »    Full Text »    PDF »
The Interleukin-4 Receptor Activates STAT5 by a Mechanism That Relies upon Common gamma -Chain.
A. Lischke, R. Moriggl, S. Brandlein, S. Berchtold, W. Kammer, W. Sebald, B. Groner, X. Liu, L. Hennighausen, and K. Friedrich (1998)
J. Biol. Chem. 273, 31222-31229
   Abstract »    Full Text »    PDF »
Interleukin 2-mediated Uncoupling of T Cell Receptor alpha /beta from CD3 Signaling.
L. Haughn, B. Leung, L. Boise, A. Veillette, C. Thompson, and M. Julius (1998)
J. Exp. Med. 188, 1575-1586
   Abstract »    Full Text »    PDF »
Functional Cooperation of the Interleukin-2 Receptor beta  Chain and Jak1 in Phosphatidylinositol 3-Kinase Recruitment and Phosphorylation.
T.-S. Migone, S. Rodig, N. A. Cacalano, M. Berg, R. D. Schreiber, and W. J. Leonard (1998)
Mol. Cell. Biol. 18, 6416-6422
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Role of Akt and c-Jun N-terminal Kinase 2 in Apoptosis Induced by Interleukin-4 Deprivation.
A. Cerezo, C. Martínez-A, D. Lanzarot, S. Fischer, T. F. Franke, and A. Rebollo (1998)
Mol. Biol. Cell 9, 3107-3118
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Molecular Mapping with Functional Antibodies Localizes Critical Sites on the Human IL Receptor Common {gamma} ({gamma}c) Chain.
N. Raskin, A. Jakubowski, I. Sizing, D. L. Olson, S. L. Kalled, C. A. Hession, C. D. Benjamin, D. P. Baker, and L. C. Burkly (1998)
J. Immunol. 161, 3474-3483
   Abstract »    Full Text »    PDF »
Activation of E2F-mediated Transcription by Human T-cell Leukemia Virus Type I Tax Protein in a p16INK4A-negative T-cell Line.
I. Lemasson, S. Thebault, C. Sardet, C. Devaux, and J.-M. Mesnard (1998)
J. Biol. Chem. 273, 23598-23604
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Endocytosis of the Common Cytokine Receptor gamma c Chain. IDENTIFICATION OF SEQUENCES INVOLVED IN INTERNALIZATION AND DEGRADATION.
E. Morelon and A. Dautry-Varsat (1998)
J. Biol. Chem. 273, 22044-22051
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Differential Regulation of the Janus Kinase-STAT Pathway and Biologic Function of IL-13 in Primary Human NK and T Cells: A Comparative Study with IL-4.
C.-R. Yu, R. A. Kirken, M. G. Malabarba, H. A. Young, and J. R. Ortaldo (1998)
J. Immunol. 161, 218-227
   Abstract »    Full Text »    PDF »
Cutting Edge: JAK3 Activation and Rescue of T Cells from HIV gp120-Induced Unresponsiveness.
N. Selliah and T. H. Finkel (1998)
J. Immunol. 160, 5697-5701
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Interleukin-2 induces beta 2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB).
J. Brockdorff, S. B. Kanner, M. Nielsen, N. Borregaard, C. Geisler, A. Svejgaard, and N. Odum (1998)
PNAS 95, 6959-6964
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Human and Simian T-Cell Leukemia Viruses Type 2 (HTLV-2 and STLV-2pan-p) Transform T Cells Independently of Jak/STAT Activation.
J. C. Mulloy, T.-S. Migone, T. M. Ross, N. Ton, P. L. Green, W. J. Leonard, and G. Franchini (1998)
J. Virol. 72, 4408-4412
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Delineation of the Regions of Interleukin-2 (IL-2) Receptor beta  Chain Important for Association of Jak1 and Jak3. Jak1-INDEPENDENT FUNCTIONAL RECRUITMENT OF Jak3 TO IL-2Rbeta.
M.-h. Zhu, J. A. Berry, S. M. Russell, and W. J. Leonard (1998)
J. Biol. Chem. 273, 10719-10725
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Regulation of Interleukin-13 Receptor Constituents on Mature Human B Lymphocytes.
H. Ogata, D. Ford, N. Kouttab, T. C. King, N. Vita, A. Minty, J. Stoeckler, D. Morgan, C. Girasole, J. W. Morgan, et al. (1998)
J. Biol. Chem. 273, 9864-9871
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A Role for the Insulin-Interleukin (IL)-4 Receptor Motif of the IL-4 Receptor alpha -Chain in Regulating Activation of the Insulin Receptor Substrate 2 and Signal Transducer and Activator of Transcription 6 Pathways. ANALYSIS BY MUTAGENESIS.
H. Y. Wang, J. Zamorano, and A. D. Keegan (1998)
J. Biol. Chem. 273, 9898-9905
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Involvement of the IL-2 Receptor {gamma}-Chain ({gamma}c) in the Control by IL-4 of Human Monocyte and Macrophage Proinflammatory Mediator Production.
C. S. Bonder, H. L. Dickensheets, J. J. Finlay-Jones, R. P. Donnelly, and P. H. Hart (1998)
J. Immunol. 160, 4048-4056
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Heteromerization of the gamma c Chain with the Interleukin-9 Receptor alpha  Subunit Leads to STAT Activation and Prevention of Apoptosis.
J. H. Bauer, K. D. Liu, Y. You, S. Y. Lai, and M. A. Goldsmith (1998)
J. Biol. Chem. 273, 9255-9260
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Stat Proteins Control Lymphocyte Proliferation by Regulating p27Kip1 Expression.
M. H. Kaplan, C. Daniel, U. Schindler, and M. J. Grusby (1998)
Mol. Cell. Biol. 18, 1996-2003
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Regulation of Cell Growth by IL-2: Role of STAT5 in Protection from Apoptosis But Not in Cell Cycle Progression.
J. Zamorano, H. Y. Wang, R. Wang, Y. Shi, G. D. Longmore, and A. D. Keegan (1998)
J. Immunol. 160, 3502-3512
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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.
T.-S. Migone, N. A. Cacalano, N. Taylor, T. Yi, T. A. Waldmann, and J. A. Johnston (1998)
PNAS 95, 3845-3850
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Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.
T. Miyazaki, A. Takaoka, L. Nogueira, I. Dikic, H. Fujii, S. Tsujino, Y. Mitani, M. Maeda, J. Schlessinger, and T. Taniguchi (1998)
Genes & Dev. 12, 770-775
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Requirement for Jak3 in Mature T Cells: Its Role in Regulation of T Cell Homeostasis.
S. J. Sohn, K. A. Forbush, N. Nguyen, B. Witthuhn, T. Nosaka, J. N. Ihle, and R. M. Perlmutter (1998)
J. Immunol. 160, 2130-2138
   Abstract »    Full Text »    PDF »
Inhibition of JAK3 and STAT6 Tyrosine Phosphorylation by the Immunosuppressive Drug Leflunomide Leads to a Block in IgG1 Production.
K. Siemasko, A. S-F. Chong, H.-M. Jack, H. Gong, J. W. Williams, and A. Finnegan (1998)
J. Immunol. 160, 1581-1588
   Abstract »    Full Text »    PDF »


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