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  • Receptor, Ciliary Neurotrophic Factor  (5)
  • American Association for the Advancement of Science (AAAS)  (5)
  • 1
    Publication Date: 1997-10-23
    Description: A mechanism by which members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras-mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonni, A -- Sun, Y -- Nadal-Vicens, M -- Bhatt, A -- Frank, D A -- Rozovsky, I -- Stahl, N -- Yancopoulos, G D -- Greenberg, M E -- NIHP30-HD 18655/HD/NICHD NIH HHS/ -- R01 CA43855/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 17;278(5337):477-83.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9334309" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Astrocytes/*cytology/drug effects/metabolism ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cells, Cultured ; Cerebral Cortex/*cytology/embryology ; Ciliary Neurotrophic Factor ; Cytokine Receptor gp130 ; DNA-Binding Proteins/*metabolism ; Dimerization ; Glial Fibrillary Acidic Protein/biosynthesis ; Growth Inhibitors/metabolism/pharmacology ; *Interleukin-6 ; Janus Kinase 1 ; Leukemia Inhibitory Factor ; Leukemia Inhibitory Factor Receptor alpha Subunit ; Lymphokines/metabolism/pharmacology ; Membrane Glycoproteins/metabolism ; Nerve Growth Factors/pharmacology ; Nerve Tissue Proteins/metabolism/pharmacology ; Platelet-Derived Growth Factor/pharmacology ; Protein-Tyrosine Kinases/*metabolism ; Rats ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, Ciliary Neurotrophic Factor ; Receptors, Cytokine/metabolism ; Receptors, Nerve Growth Factor/metabolism ; Receptors, OSM-LIF ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; *Signal Transduction ; Stem Cells/cytology ; Trans-Activators/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-11-24
    Description: Some growth factors are therapeutically useful partly because restricted expression of their receptors limits their action to particular cell types. However, no unique stimulatory factor is known for many clinically relevant cell types, such as CD34+ hematopoietic stem cells. Here, soluble alpha receptor (R alpha) components for interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) were targeted in an active form to cells expressing surface markers such as CD34 or CD45, thereby rendering those cells responsive to IL-6 or CNTF. The targeting of R alpha components may provide the means to create "designer" cytokines that activate a desired cell type expressing a specific cell surface marker.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Economides, A N -- Ravetch, J V -- Yancopoulos, G D -- Stahl, N -- New York, N.Y. -- Science. 1995 Nov 24;270(5240):1351-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481821" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Antigens, CD/immunology/*metabolism ; Antigens, CD34/analysis ; Antigens, CD45/analysis ; Cell Division ; Cell Line ; Cell Membrane/*metabolism ; Ciliary Neurotrophic Factor ; Cytokine Receptor gp130 ; *Growth Inhibitors ; Humans ; Immunoglobulin Fc Fragments ; Interleukin-6/*pharmacology ; Leukemia Inhibitory Factor ; Leukemia Inhibitory Factor Receptor alpha Subunit ; *Lymphokines ; Membrane Glycoproteins/metabolism ; Nerve Tissue Proteins/*pharmacology ; Phosphorylation ; Receptor, Ciliary Neurotrophic Factor ; Receptors, Cytokine/metabolism ; Receptors, Fc ; Receptors, Interleukin/immunology/*metabolism ; Receptors, Interleukin-6 ; Receptors, Nerve Growth Factor/immunology/*metabolism ; Receptors, OSM-LIF ; Recombinant Fusion Proteins/metabolism ; Solubility ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1993-03-19
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S -- Aldrich, T H -- Ip, N Y -- Stahl, N -- Scherer, S -- Farruggella, T -- DiStefano, P S -- Curtis, R -- Panayotatos, N -- Gascan, H -- New York, N.Y. -- Science. 1993 Mar 19;259(5102):1736-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7681218" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cell Membrane/metabolism ; Ciliary Neurotrophic Factor ; Cloning, Molecular ; Gene Expression ; Glycosylphosphatidylinositols/metabolism ; Growth Inhibitors/pharmacology ; Hematopoietic Stem Cells/cytology/drug effects ; Humans ; Interleukin-6/pharmacology ; Leukemia Inhibitory Factor ; Lymphokines/pharmacology ; Mice ; Muscle Denervation ; Muscles/innervation/metabolism ; Nerve Tissue Proteins/*pharmacology ; Phosphatidylinositol Diacylglycerol-Lyase ; Phosphoric Diester Hydrolases/metabolism ; Phosphotyrosine ; RNA, Messenger/genetics ; Rats ; Receptor, Ciliary Neurotrophic Factor ; Receptors, Cell Surface/chemistry/*physiology ; Signal Transduction/physiology ; Tumor Cells, Cultured ; Tyrosine/analogs & derivatives/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1993-06-18
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S -- Aldrich, T H -- Stahl, N -- Pan, L -- Taga, T -- Kishimoto, T -- Ip, N Y -- Yancopoulos, G D -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1805-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8390097" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigens, CD ; Cell Line ; Cytokine Receptor gp130 ; Growth Inhibitors/pharmacology ; Interleukin-6/pharmacology ; Leukemia Inhibitory Factor ; Lymphokines/pharmacology ; Macromolecular Substances ; Membrane Glycoproteins/chemistry/*metabolism ; Models, Biological ; Nerve Growth Factors ; Nerve Tissue Proteins/pharmacology ; Phosphorylation ; Receptor, Ciliary Neurotrophic Factor ; Receptors, Cell Surface/chemistry/*metabolism ; *Receptors, Cytokine ; Receptors, Immunologic/chemistry/*metabolism ; Receptors, Interleukin-6 ; Receptors, OSM-LIF ; *Signal Transduction ; Tumor Cells, Cultured ; Tyrosine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1994-01-07
    Description: A recently defined family of cytokines, consisting of ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), and interleukin-6 (IL-6), utilize the Jak-Tyk family of cytoplasmic tyrosine kinases. The beta receptor components for this cytokine family, gp130 and LIF receptor beta, constitutively associate with Jak-Tyk kinases. Activation of these kinases occurs as a result of ligand-induced dimerization of the receptor beta components. Unlike other cytokine receptors studied to date, the receptors for the CNTF cytokine family utilize all known members of the Jak-Tyk family, but induce distinct patterns of Jak-Tyk phosphorylation in different cell lines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stahl, N -- Boulton, T G -- Farruggella, T -- Ip, N Y -- Davis, S -- Witthuhn, B A -- Quelle, F W -- Silvennoinen, O -- Barbieri, G -- Pellegrini, S -- P30 CA21765/CA/NCI NIH HHS/ -- R01 DK42932/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1994 Jan 7;263(5143):92-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8272873" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigens, CD ; Cell Line ; Ciliary Neurotrophic Factor ; Cytokine Receptor gp130 ; Cytokines/metabolism/*pharmacology ; Enzyme Activation ; *Growth Inhibitors ; *Interleukin-6 ; Janus Kinase 1 ; Janus Kinase 2 ; Leukemia Inhibitory Factor ; *Lymphokines ; Membrane Glycoproteins/*metabolism ; Nerve Tissue Proteins/metabolism/pharmacology ; Oncostatin M ; Peptides/metabolism/pharmacology ; Phosphorylation ; Protein-Tyrosine Kinases/*metabolism ; Proteins/metabolism ; *Proto-Oncogene Proteins ; Receptor, Ciliary Neurotrophic Factor ; Receptors, Cytokine/*metabolism ; Receptors, Growth Factor/metabolism ; Receptors, Interleukin/metabolism ; Receptors, Interleukin-6 ; Receptors, OSM-LIF ; Receptors, Oncostatin M ; Tyrosine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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