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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
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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- Role of Interleukin (IL)-2 Receptor beta -Chain Subdomains and Shc in p38 Mitogen-activated Protein (MAP) Kinase and p54 MAP Kinase (Stress-activated Protein Kinase/c-Jun N-terminal Kinase) Activation. IL-2-DRIVEN PROLIFERATION IS INDEPENDENT OF p38 AND p54 MAP KINASE ACTIVATION.
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Mol. Cell. Biol.
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- IgE Hyperproduction Through Enhanced Tyrosine Phosphorylation of Janus Kinase 3 in NC/Nga Mice, a Model for Human Atopic Dermatitis.
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- Functional Role of Interleukin-4 (IL-4) and IL-7 in the Development of X-Linked Severe Combined Immunodeficiency.
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Blood
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- Signaling via the IL-2 and IL-7 Receptors from the Membrane to the Nucleus.
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Cold Spring Harb Symp Quant Biol
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- 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
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- Interleukin 7 Receptor Control of T Cell Receptor {gamma} Gene Rearrangement: Role of Receptor-associated Chains and Locus Accessibility.
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- The Interleukin-4 Receptor Activates STAT5 by a Mechanism That Relies upon Common gamma -Chain.
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- Interleukin 2-mediated Uncoupling of T Cell Receptor {alpha}/{beta} from CD3 Signaling.
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- Functional Cooperation of the Interleukin-2 Receptor beta Chain and Jak1 in Phosphatidylinositol 3-Kinase Recruitment and Phosphorylation.
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Mol. Cell. Biol.
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- Role of Akt and c-Jun N-terminal Kinase 2 in Apoptosis Induced by Interleukin-4 Deprivation.
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Mol. Biol. Cell
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- Molecular Mapping with Functional Antibodies Localizes Critical Sites on the Human IL Receptor Common {gamma} ({gamma}c) Chain.
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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.
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J. Immunol.
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PNAS
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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.
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- Regulation of Interleukin-13 Receptor Constituents on Mature Human B Lymphocytes.
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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.
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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.
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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.
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- Stat Proteins Control Lymphocyte Proliferation by Regulating p27Kip1 Expression.
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Mol. Cell. Biol.
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- Regulation of Cell Growth by IL-2: Role of STAT5 in Protection from Apoptosis But Not in Cell Cycle Progression.
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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.
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PNAS
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- Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.
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Genes & Dev.
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