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Science 18 June 1993:
Vol. 260. no. 5115, pp. 1805 - 1808
DOI: 10.1126/science.8390097

Articles

Science, Vol 260, Issue 5115, 1805-1808
Copyright © 1993 by American Association for the Advancement of Science


articles

LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor

S Davis, TH Aldrich, N Stahl, L Pan, T Taga, T Kishimoto, NY Ip, and GD Yancopoulos

Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.

The ciliary neurotrophic factor (CNTF) receptor complex is shown here to include the CNTF binding protein (CNTFR alpha) as well as the components of the leukemia inhibitory factor (LIF) receptor, LIFR beta (the LIF binding protein) and gp130 [the signal transducer of interleukin-6 (IL-6)]. Thus, the conversion of a bipartite LIF receptor into a tripartite CNTF receptor apparently occurs by the addition of the specificity-conferring element CNTFR alpha. Both CNTF and LIF trigger the association of initially separate receptor components, which in turn results in tyrosine phosphorylation of receptor subunits. Unlike the IL-6 receptor complex in which homodimerization of gp130 appears to be critical for signal initiation, signaling by the CNTF and LIF receptor complexes depends on the heterodimerization of gp130 with LIFR beta. Ligand-induced dimerization of signal-transducing receptor components, also seen with receptor tyrosine kinases, may provide a general mechanism for the transmission of a signal across the cell membrane.


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   Abstract »    Full Text »    PDF »
An Antagonist for the Leukemia Inhibitory Factor Receptor Inhibits Leukemia Inhibitory Factor, Cardiotrophin-1, Ciliary Neurotrophic Factor, and Oncostatin M.
A. B. Vernallis, K. R. Hudson, and J. K. Heath (1997)
J. Biol. Chem. 272, 26947-26952
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Regulation of Gliogenesis in the Central Nervous System by the JAK-STAT Signaling Pathway.
A. Bonni, Y. Sun, M. Nadal-Vicens, A. Bhatt, D. A. Frank, I. Rozovsky, N. Stahl, G. D. Yancopoulos, and M. E. Greenberg (1997)
Science 278, 477-483
   Abstract »    Full Text »
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.
J. M. Woodcock, B. J. McClure, F. C. Stomski, M. J. Elliott, C. J. Bagley, and A. F. Lopez (1997)
Blood 90, 3005-3017
   Abstract »    Full Text »    PDF »
Ciliary Neurotrophic Factor Stimulates the Phosphorylation of Two Forms of STAT3 in Chick Ciliary Ganglion Neurons.
M. A. Wishingrad, S. Koshlukova, and S. W. Halvorsen (1997)
J. Biol. Chem. 272, 19752-19757
   Abstract »    Full Text »    PDF »
HNMP-1: A Novel Hematopoietic and Neural Membrane Protein Differentially Regulated in Neural Development and Injury.
L. M. Bolin, T. McNeil, L. A. Lucian, B. DeVaux, K. Franz-Bacon, D. M. Gorman, S. Zurawski, R. Murray, and T. K. McClanahan (1997)
J. Neurosci. 17, 5493-5502
   Abstract »    Full Text »    PDF »
Influence of Subunit Combinations on Signaling by Receptors for Oncostatin M, Leukemia Inhibitory Factor, and Interleukin-6.
K. K. Kuropatwinski, C. De Imus, D. Gearing, H. Baumann, and B. Mosley (1997)
J. Biol. Chem. 272, 15135-15144
   Abstract »    Full Text »    PDF »
Interleukin-11: Review of Molecular, Cell Biology, and Clinical Use.
X. Du and D. A. Williams (1997)
Blood 89, 3897-3908
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A Common Pro-opiomelanocortin-binding Element Mediates Leukemia Inhibitory Factor and Corticotropin-releasing Hormone Transcriptional Synergy.
C. Bousquet, D. W. Ray, and S. Melmed (1997)
J. Biol. Chem. 272, 10551-10557
   Abstract »    Full Text »    PDF »
Integration of Jak-Stat and AP-1 Signaling Pathways at the Vasoactive Intestinal Peptide Cytokine Response Element Regulates Ciliary Neurotrophic Factor-dependent Transcription.
A. Symes, T. Gearan, J. Eby, and J. S. Fink (1997)
J. Biol. Chem. 272, 9648-9654
   Abstract »    Full Text »    PDF »
Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130.
A. Kumanogoh, S. Marukawa, T. Kumanogoh, H. Hirota, K. Yoshida, I.-S. Lee, T. Yasui, K. Yoshida, T. Taga, and T. Kishimoto (1997)
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.
C. J. Bagley, J. M. Woodcock, F. C. Stomski, and A. F. Lopez (1997)
Blood 89, 1471-1482
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Signaling of the Cardiotrophin-1 Receptor. EVIDENCE FOR A THIRD RECEPTOR COMPONENT.
O. Robledo, M. Fourcin, S. Chevalier, C. Guillet, P. Auguste, A. Pouplard-Barthelaix, D. Pennica, and H. Gascan (1997)
J. Biol. Chem. 272, 4855-4863
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Differential Regulation of Ciliary Neurotrophic Factor (CNTF) and CNTF Receptor alpha  Expression in Astrocytes and Neurons of the Fascia Dentata after Entorhinal Cortex Lesion.
M.-Y. Lee, T. Deller, M. Kirsch, M. Frotscher, and H.-D. Hofmann (1997)
J. Neurosci. 17, 1137-1146
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Induction of the Intronic Enhancer of the Human Ciliary Neurotrophic Factor Receptor (CNTFRalpha ) Gene by the TR4 Orphan Receptor. A MEMBER OF STEROID RECEPTOR SUPERFAMILY.
W.-J. Young, S. M. Smith, and C. Chang (1997)
J. Biol. Chem. 272, 3109-3116
   Abstract »    Full Text »    PDF »
Dual Oncostatin M (OSM) Receptors. CLONING AND CHARACTERIZATION OF AN ALTERNATIVE SIGNALING SUBUNIT CONFERRING OSM-SPECIFIC RECEPTOR ACTIVATION.
B. Mosley, C. De Imus, D. Friend, N. Boiani, B. Thoma, L. S. Park, and D. Cosman (1996)
J. Biol. Chem. 271, 32635-32643
   Abstract »    Full Text »    PDF »
Single factors direct the differentiation of stem cells from the fetal and adult central nervous system..
K K Johe, T G Hazel, T Muller, M M Dugich-Djordjevic, and R D McKay (1996)
Genes & Dev. 10, 3129-3140
   Abstract »    PDF »
Functional Expression of Soluble Human Interleukin-11 (IL-11) Receptor alpha and Stoichiometry of in Vitro IL-11 Receptor Complexes with gp130.
P. Neddermann, R. Graziani, G. Ciliberto, and G. Paonessa (1996)
J. Biol. Chem. 271, 30986-30991
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gp130-mediated Signal Transduction in Embryonic Stem Cells Involves Activation of Jak and Ras/Mitogen-activated Protein Kinase Pathways.
M. Ernst, A. Oates, and A. R. Dunn (1996)
J. Biol. Chem. 271, 30136-30143
   Abstract »    Full Text »    PDF »
A Single Tyrosine Residue in the Membrane-proximal Domain of the Granulocyte-Macrophage Colony-stimulating Factor, Interleukin (IL)-3, and IL-5 Receptor Common beta -Chain Is Necessary and Sufficient for High Affinity Binding and Signaling by All Three Ligands.
J. M. Woodcock, C. J. Bagley, B. Zacharakis, and A. F. Lopez (1996)
J. Biol. Chem. 271, 25999-26006
   Abstract »    Full Text »    PDF »
Alanine Substitution for Thr268 and Asp269 of Soluble Ciliary Neurotrophic Factor (CNTF) Receptor alpha Component Defines a Specific Antagonist for the CNTF Response.
P. Auguste, O. Robledo, C. Olivier, J. Froger, V. Praloran, A. Pouplard-Barthelaix, and H. Gascan (1996)
J. Biol. Chem. 271, 26049-26056
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Ciliary Neurotrophic Factor Induces Down-regulation of Its Receptor and Desensitization of Signal Transduction Pathways in Vivo:. NON-EQUIVALENCE WITH PHARMACOLOGICAL ACTIVITY.
P. S. DiStefano, T. G. Boulton, J. L. Stark, Y. Zhu, K. M. Adryan, T. E. Ryan, and R. M. Lindsay (1996)
J. Biol. Chem. 271, 22839-22846
   Abstract »    Full Text »    PDF »
Influence of Interleukin-6 (IL-6) Dimerization on Formation of the High Affinity Hexameric IL-6·Receptor Complex.
L. D. Ward, A. Hammacher, G. J. Howlett, J. M. Matthews, L. Fabri, R. L. Moritz, E. C. Nice, J. Weinstock, and R. J. Simpson (1996)
J. Biol. Chem. 271, 20138-20144
   Abstract »    Full Text »    PDF »
Cloning and Characterization of an Ovarian-specific Protein That Associates with the Short Form of the Prolactin Receptor.
W. R. Duan, D. I.H. Linzer, and G. Gibori (1996)
J. Biol. Chem. 271, 15602-15607
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Interleukin-6 Family of Cytokines Induced Activation of Different Functional Sites Expressed by gp130 Transducing Protein.
S. Chevalier, M. Fourcin, O. Robledo, J. Wijdenes, A. Pouplard-Barthelaix, and H. Gascan (1996)
J. Biol. Chem. 271, 14764-14772
   Abstract »    Full Text »    PDF »
gp130 Transducing Receptor Cross-linking Is Sufficient to Induce Interleukin-6 Type Responses.
M. Fourcin, S. Chevalier, C. Guillet, O. Robledo, J. Froger, A. Pouplard-Barthelaix, and H. Gascan (1996)
J. Biol. Chem. 271, 11756-11760
   Abstract »    Full Text »    PDF »
Characterization of the Receptor Binding Sites of Human Leukemia Inhibitory Factor and Creation of Antagonists.
K. R. Hudson, A. B. Vernallis, and J. K. Heath (1996)
J. Biol. Chem. 271, 11971-11978
   Abstract »    Full Text »    PDF »



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