An Antagonist for the Leukemia Inhibitory Factor Receptor Inhibits Leukemia Inhibitory Factor, Cardiotrophin-1, Ciliary Neurotrophic Factor, and Oncostatin M

Autor: Keith R. Hudson, Ann B. Vernallis, John K. Heath
Rok vydání: 1997
Předmět:
endocrine system
Leukemia Inhibitory Factor Receptor alpha Subunit
Receptors
OSM-LIF
Nerve Tissue Proteins
Leukemia inhibitory factor receptor
Oncostatin M
Ciliary neurotrophic factor
Transfection
Leukemia Inhibitory Factor
Biochemistry
Cell Line
Escherichia coli
Tumor Cells
Cultured
Humans
Ciliary Neurotrophic Factor
Nerve Growth Factors
Cloning
Molecular
Receptors
Cytokine
Molecular Biology
reproductive and urinary physiology
Lymphokines
biology
Interleukin-6
Chemistry
Oncostatin M receptor
Cell Biology
Glycoprotein 130
Molecular biology
Growth Inhibitors
Recombinant Proteins
biological factors
embryonic structures
Mutagenesis
Site-Directed
Cancer research
biology.protein
Cytokines
CLCF1
Peptides
Leukemia inhibitory factor
Cell Division
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of Biological Chemistry. 272:26947-26952
ISSN: 0021-9258
1083-351X
Popis: 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.
Databáze: OpenAIRE
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