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

Ann B. Vernallis, Keith R. Hudson, John K. Heath

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)26947-26952
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number43
DOIs
Publication statusPublished - 1997

Bibliographical note

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

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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