CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130.
Ciliary neurotrophic factor (CNTF) has a variety of actions within the nervous system. While some of the actions of leukemia inhibitory factor (LIF) on neurons resemble those of CNTF, LIF also has broad actions outside of the nervous system that in many cases mimic those of interleukin-6 (IL-6). Comparison of the tyrosine phosphorylations and gene activations induced by CNTF and LIF in neuron cell lines reveals that they are indistinguishable and also very similar to signaling events that characterize LIF and IL-6 responses in hematopoietic cells. We provide a basis for the overlapping actions of these three factors by demonstrating that the shared CNTF and LIF signaling pathways involve the IL-6 signal transducing receptor component gp130. Thus, the receptor system for CNTF is surprisingly unlike those used by the nerve growth factor family of neurotrophic factors, but is instead related to those used by a subclass of hematopoietic cytokines.
Ip
N Y
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Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Nye
S H
SH
Boulton
T G
TG
Davis
S
S
Taga
T
T
Li
Y
Y
Birren
S J
SJ
Yasukawa
K
K
Kishimoto
T
T
Anderson
D J
DJ
D000818:Animals; D015703:Antigens, CD; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011971:Receptors, Immunologic / Q000187:drug effects*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors; C494201:Il6st protein, rat; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D014443:Tyrosine