An antagonist for the leukemia inhibitory factor receptor inhibits leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, and oncostatin M


The leukemia inhibitory factor receptor (LIF-R) is activated not only by LIF, but also by cardiotrophin-1, ciliary neurotrophic factor with its receptor, and oncostatin M (OSM). Each of these cytokines induces the hetero-oligomerization of LIF-R with gp130, a signal-transducing subunit shared with interleukin-6 and interleukin-11. The introduction of mutations into human LIF that reduced the affinity for gp130 while retaining affinity for LIF-R has generated antagonists for LIF. In the current study, a LIF antagonist that was free of detectable agonistic activity was tested for antagonism against the family of LIF-R ligands. On cells that express LIF-R and gp130, all LIF-R ligands were antagonized. On cells that also express OSM receptor, OSM was not antagonized, demonstrating that the antagonist is specific for LIF-R. Ligand-triggered tyrosine phosphorylation of both LIF-R and gp130 was blocked by the antagonist. The antagonist is therefore likely to work by preventing receptor oligomerization.

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Divisions: College of Health & Life Sciences > Cell & Tissue Biomedical Research
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > School of Biosciences
Additional Information: This research was originally published in the Journal of Biological Chemistry. Ann B. Vernallis, Keith R. Hudson and John K. Heath. An Antagonist for the Leukemia Inhibitory Factor Receptor Inhibits Leukemia Inhibitory Factor, Cardiotrophin-1, Ciliary Neurotrophic Factor, and Oncostatin M. J. Biol. Chem. 1997; Vol 272:26947-26952. © the American Society for Biochemistry and Molecular Biology
Uncontrolled Keywords: Cell Division,Cell Line,Ciliary Neurotrophic Factor,Cloning, Molecular,Cytokines,Escherichia coli,Growth Inhibitors,Humans,Interleukin-6,Leukemia Inhibitory Factor,Leukemia Inhibitory Factor Receptor alpha Subunit,Lymphokines,Mutagenesis, Site-Directed,Nerve Growth Factors,Nerve Tissue Proteins,Oncostatin M,Peptides,Receptors, Cytokine,Receptors, OSM-LIF,Recombinant Proteins,Transfection,Tumor Cells, Cultured
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Related URLs: http://www.jbc. ... nt/272/43/26947 (Publisher URL)
PURE Output Type: Article
Published Date: 1997
Authors: Vernallis, Ann B.
Hudson, Keith R.
Heath, John K.



Version: Published Version

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