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Science 19 March 1993:
Vol. 259. no. 5102, pp. 1736 - 1739
DOI: 10.1126/science.7681218
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Articles

Science, Vol 259, Issue 5102, 1736-1739
Copyright © 1993 by American Association for the Advancement of Science

articles

Released form of CNTF receptor alpha component as a soluble mediator of CNTF responses

S Davis, TH Aldrich, NY Ip, N Stahl, S Scherer, T Farruggella, PS DiStefano, R Curtis, N Panayotatos, H Gascan, and al. et

Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.

The alpha component of the receptor for ciliary neurotrophic factor (CNTF) differs from other known growth factor receptors in that it is anchored to cell membranes by a glycosylphosphatidylinositol linkage. One possible function of this type of linkage is to allow for the regulated release of this receptor component. Cell lines not normally responsive to CNTF responded to treatment with a combination of CNTF and a soluble form of the CNTF alpha receptor component. These findings not only demonstrate that the CNTF receptor alpha chain is a required component of the functional CNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand. Potential physiological roles for the soluble CNTF receptor are suggested by its presence in cerebrospinal fluid and by its release from skeletal muscle in response to peripheral nerve injury.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Ciliary Neurotrophic Factor, Cardiotrophin-like Cytokine, and Neuropoietin Share a Conserved Binding Site on the Ciliary Neurotrophic Factor Receptor {alpha} Chain.
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Neuropoietin Attenuates Adipogenesis and Induces Insulin Resistance in Adipocytes.
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Neuroinflammation facilitates LIF entry into brain: role of TNF.
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Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin-31 Shared Receptor.
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Mechanisms of Soluble Cytokine Receptor Generation.
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GPL, a Novel Cytokine Receptor Related to GP130 and Leukemia Inhibitory Factor Receptor.
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The Regulation and Activation of Ciliary Neurotrophic Factor Signaling Proteins in Adipocytes.
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Cytokine-induced Nuclear Factor Kappa B Activation Promotes the Survival of Developing Neurons.
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J. Cell Biol. 148, 325-332
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Identification of the soluble granulocyte-macrophage colony stimulating factor receptor protein in vivo.
F. Sayani, F. A. Montero-Julian, V. Ranchin, J. M. Prevost, S. Flavetta, W. Zhu, R. C. Woodman, H. Brailly, and C. B. Brown (2000)
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M. Peters, A. M. Muller, and S. Rose-John (1998)
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C. Renne, K.-J. Kallen, J. Mullberg, T. Jostock, J. Grotzinger, and S. Rose-John (1998)
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The Membrane Proximal Cytokine Receptor Domain of the Human Interleukin-6 Receptor Is Sufficient for Ligand Binding but Not for gp130 Association.
S. Ozbek, J. Grotzinger, B. Krebs, M. Fischer, A. Wollmer, T. Jostock, J. Mullberg, and S. Rose-John (1998)
J. Biol. Chem. 273, 21374-21379
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Cytokine-Like Factor-1, a Novel Soluble Protein, Shares Homology with Members of the Cytokine Type I Receptor Family.
G. C. A. Elson, P. Graber, C. Losberger, S. Herren, D. Gretener, L. N. Menoud, T. N. C. Wells, M. H. Kosco-Vilbois, and J.-F. Gauchat (1998)
J. Immunol. 161, 1371-1379
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Identification and Characterization of Two Distinct Truncated Forms of gp130 and a Soluble Form of Leukemia Inhibitory Factor Receptor alpha -Chain in Normal Human Urine and Plasma.
J.-G. Zhang, Y. Zhang, C. M. Owczarek, L. D. Ward, R. L. Moritz, R. J. Simpson, K. Yasukawa, and N. A. Nicola (1998)
J. Biol. Chem. 273, 10798-10805
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Cell Activation Mediated by Glycosylphosphatidylinositol-Anchored or Transmembrane Forms of CD14.
J. Pugin, V. V. Kravchenko, J.-D. Lee, L. Kline, R. J. Ulevitch, and P. S. Tobias (1998)
Infect. Immun. 66, 1174-1180
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Sexual Dimorphism in the Spinal Cord Is Absent in Mice Lacking the Ciliary Neurotrophic Factor Receptor.
N. G. Forger, M. L. Howell, L. Bengston, L. MacKenzie, T. M. DeChiara, and G. D. Yancopoulos (1997)
J. Neurosci. 17, 9605-9612
   Abstract »    Full Text »    PDF »
A Sweat Gland-derived Differentiation Activity Acts through Known Cytokine Signaling Pathways.
B. A. Habecker, A. J. Symes, N. Stahl, N. J. Francis, A. Economides, J. S. Fink, G. D. Yancopoulos, and S. C. Landis (1997)
J. Biol. Chem. 272, 30421-30428
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Hyperleptinemia of Pregnancy Associated with the Appearance of a Circulating Form of the Leptin Receptor.
O. Gavrilova, V. Barr, B. Marcus-Samuels, and M. Reitman (1997)
J. Biol. Chem. 272, 30546-30551
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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
   Abstract »    Full Text »    PDF »
Gp60 Activation Mediates Albumin Transcytosis in Endothelial Cells by Tyrosine Kinase-dependent Pathway.
C. Tiruppathi, W. Song, M. Bergenfeldt, P. Sass, and A. B. Malik (1997)
J. Biol. Chem. 272, 25968-25975
   Abstract »    Full Text »    PDF »
Agonistic and Antagonistic Variants of Ciliary Neurotrophic Factor (CNTF) Reveal Functional Differences between Membrane-bound and Soluble CNTF alpha -Receptor.
A. Di Marco, I. Gloaguen, A. Demartis, I. Saggio, R. Graziani, G. Paonessa, and R. Laufer (1997)
J. Biol. Chem. 272, 23069-23075
   Abstract »    Full Text »    PDF »
Apolipoprotein E Binds to and Potentiates the Biological Activity of Ciliary Neurotrophic Factor.
C. R. Gutman, W. J. Strittmatter, K. H. Weisgraber, and W. D. Matthew (1997)
J. Neurosci. 17, 6114-6121
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
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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
   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
   Abstract »    Full Text »    PDF »
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 »
Ligand-independent Cell Surface Expression of the Human Soluble Granulocyte-Macrophage Colony-stimulating Factor Receptor alpha Subunit Depends on Co-expression of the Membrane-associated Receptor beta Subunit.
E. W. Murray, C. Pihl, A. Morcos, and C. B. Brown (1996)
J. Biol. Chem. 271, 15330-15335
   Abstract »    Full Text »    PDF »
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 »
Cardiotrophin-1 Activates a Distinct Form of Cardiac Muscle Cell Hypertrophy.
K. C. Wollert, T. Taga, M. Saito, M. Narazaki, T. Kishimoto, C. C. Glembotski, A. B. Vernallis, J. K. Heath, D. Pennica, W. I. Wood, et al. (1996)
J. Biol. Chem. 271, 9535-9545
   Abstract »    Full Text »    PDF »
Designer Cytokines: Targeting Actions to Cells of Choice.
A. N. Economides, J. V. Ravetch, G. D. Yancopoulos, and N. Stahl (1995)
Science 270, 1351-1353
   Abstract »    PDF »
Localization of Functional Receptor Epitopes on the Structure of Ciliary Neurotrophic Factor Indicates a Conserved, Function-related Epitope Topography among Helical Cytokines.
N. Panayotatos, E. Radziejewska, A. Acheson, R. Somogyi, A. Thadani, W. A. Hendrickson, and N. Q. McDonald (1995)
J. Biol. Chem. 270, 14007-14014
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Characterization of Recombinant Extracellular Domain of Human Interleukin-10 Receptor.
J. C. Tan, S. Braun, H. Rong, R. DiGiacomo, E. Dolphin, S. Baldwin, S. K. Narula, P. J. Zavodny, and C.-C. Chou (1995)
J. Biol. Chem. 270, 12906-12911
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Cardiotrophin-1.
D. Pennica, K. J. Shaw, T. A. Swanson, M. W. Moore, D. L. Shelton, K. A. Zioncheck, A. Rosenthal, T. Taga, N. F. Paoni, and W. I. Wood (1995)
J. Biol. Chem. 270, 10915-10922
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Analysis of function and expression of the chick GPA receptor (GPAR alpha) suggests multiple roles in neuronal development.
S Heller, T. Finn, J Huber, R Nishi, M Geissen, A. Puschel, and H Rohrer (1995)
Development 121, 2681-2693
   Abstract »    PDF »
Binding Characteristics of Ciliary Neurotrophic Factor to Sympathetic Neurons and Neuronal Cell Lines.
V. Wong, D. Pearsall, R. Arriaga, N. Y. Ip, N. Stahl, and R. M. Lindsay (1995)
J. Biol. Chem. 270, 313-318
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Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.
N Stahl, T. Boulton, T Farruggella, N. Ip, S Davis, B. Witthuhn, F. Quelle, O Silvennoinen, G Barbieri, S Pellegrini, et al. (1994)
Science 263, 92-95
   Abstract »    PDF »
LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor.
S Davis, T. Aldrich, N Stahl, L Pan, T Taga, T Kishimoto, N. Ip, and G. Yancopoulos (1993)
Science 260, 1805-1808
   Abstract »    PDF »
Ciliary neurotrophic factor maintains the pluripotentiality of embryonic stem cells.
J. Conover, N. Ip, W. Poueymirou, B Bates, M. Goldfarb, T. DeChiara, and G. Yancopoulos (1993)
Development 119, 559-565
   Abstract »    PDF »
Signaling Pathways Recruited by the Cardiotrophin-like Cytokine/Cytokine-like Factor-1 Composite Cytokine. SPECIFIC REQUIREMENT OF THE MEMBRANE-BOUND FORM OF CILIARY NEUROTROPHIC FACTOR RECEPTOR alpha COMPONENT.
E. Lelievre, H. Plun-Favreau, S. Chevalier, J. Froger, C. Guillet, G. C. A. Elson, J.-F. Gauchat, and H. Gascan (2001)
J. Biol. Chem. 276, 22476-22484
   Abstract »    Full Text »    PDF »
From the Cover: Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity.
P. D. Lambert, K. D. Anderson, M. W. Sleeman, V. Wong, J. Tan, A. Hijarunguru, T. L. Corcoran, J. D. Murray, K. E. Thabet, G. D. Yancopoulos, et al. (2001)
PNAS 98, 4652-4657
   Abstract »    Full Text »    PDF »


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