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Science 18 June 1993: Vol. 260. no. 5115, pp. 1808 - 1810 DOI: 10.1126/science.8511589
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Articles
Science, Vol 260, Issue 5115, 1808-1810
Copyright © 1993 by American Association for the Advancement of Science
IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase
M Murakami,
M Hibi,
N Nakagawa,
T Nakagawa,
K Yasukawa,
K Yamanishi,
T Taga,
and
T Kishimoto
Institute for Molecular and Cellular Biology, Osaka University, Japan.
The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130. The IL-6-induced gp130 homodimer appears to be similar in function to the heterodimer formed between the leukemia inhibitory factor (LIF) receptor (LIFR) and gp130 in response to the LIF or ciliary neurotrophic factor (CNTF). Thus, a general first step in IL-6-related cytokine signaling may be the dimerization of signal-transducing molecules and activation of associated tyrosine kinases.
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PNAS
95, 3251-3256
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- Identification of a Cys Motif in the Common beta Chain of the Interleukin 3, Granulocyte-Macrophage Colony-stimulating Factor, and Interleukin 5 Receptors Essential for Disulfide-linked Receptor Heterodimerization and Activation of All Three Receptors.
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Blood
91, 3-21
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272, 30421-30428
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- The Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Exists as a Preformed Receptor Complex That Can Be Activated by GM-CSF, Interleukin-3, or Interleukin-5.
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Blood
90, 3005-3017
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- Molecular Modeling-guided Mutagenesis of the Extracellular Part of gp130 Leads to the Identification of Contact Sites in the Interleukin-6 (IL-6)·IL-6 receptor·gp130 Complex.
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272, 23748-23757
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272, 19625-19631
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82, 2143-2147
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PNAS
94, 2478-2482
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- The Structural and Functional Basis of Cytokine Receptor Activation: Lessons From the Common beta Subunit of the Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-3 (IL-3), and IL-5 Receptors.
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Blood
89, 1471-1482
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Blood
89, 1319-1333
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Blood
89, 842-852
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Blood
89, 355-369
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271, 32635-32643
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271, 30986-30991
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271, 12999-13007
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271, 13023-13032
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271, 11756-11760
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271, 9535-9545
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271, 7281-7284
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271, 5464-5473
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- A Di-leucine Motif and an Upstream Serine in the Interleukin-6 (IL-6) Signal Transducer gp130 Mediate Ligand-induced Endocytosis and Down-regulation of the IL-6 Receptor.
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271, 5487-5494
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Development
122, 1235-1242
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