Oncostatin M Regulates the Synthesis and Turnover of gp130, Leukemia Inhibitory Factor Receptor α, and Oncostatin M Receptor β by Distinct Mechanisms
The cytokine receptor subunits gp130, leukemia inhibitory factor receptor α (LIFRα), and oncostatin M receptor β (OSMRβ) transduce OSM signals that regulate gene expression and cell proliferation. After ligand binding and activation of the Janus protein-tyrosine kinase/STAT and mitogen-activated...
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Published in | The Journal of biological chemistry Vol. 276; no. 50; p. 47038 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
14.12.2001
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Online Access | Get full text |
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Summary: | The cytokine receptor subunits gp130, leukemia inhibitory factor receptor α (LIFRα), and oncostatin M receptor β (OSMRβ) transduce
OSM signals that regulate gene expression and cell proliferation. After ligand binding and activation of the Janus protein-tyrosine
kinase/STAT and mitogen-activated protein kinase signal transduction pathways, negative feedback processes are recruited.
These processes attenuate receptor action by suppression of cytokine signaling and by down-regulation of receptor protein
expression. This study demonstrates that in human fibroblasts or epithelial cells, OSM first decreases the level of gp130,
LIFRα, and OSMRβ by ligand-induced receptor degradation and then increases the level of the receptors by enhanced synthesis.
The transcriptional induction of gp130 gene by OSM involves STAT3. Various cell lines expressing receptor subunits to the
different interleukin-6 class cytokines revealed that only LIFRα degradation is promoted by activated ERK and that degradation
of gp130, OSMRβ, and a fraction of LIFRα involves mechanisms that are separate from signal transduction. These mechanisms
include ligand-mediated dimerization, internalization, and endosomal/lysosomal degradation. Proteosomal degradation appears
to involve a fraction of receptor subunit proteins that are ubiquitinated independently of ligand binding. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M107971200 |