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Published June 26, 1992 | public
Journal Article

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.

Additional Information

© 1992 by Cell Press. Received March 6, 1992; Revised April 22, 1992. We thank Drs. L. S. Schleifer. M. E. Furth, and T. H. Aldrich and the entire Discovery group at Regeneron for their enthusiastic support and insightful scientific input. We also thank L. Pan, J. McClain, K. Mattsson, N. Lindsay, J. Ciliberti, and L. Defeo for technical assistance, Dr. M. J. Macchi for cell culture, Dr. B. Hoffmann-Liebermann for providing us with Ml cells, Dr. L. Greene for the tisll probe, and Drs. A. Miyajima. H. Gascan, and R. Wall for helpful discussions. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.

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