Stimulation of Leukemia Inhibitory Factor Receptor Degradation by Extracellular Signal-regulated Kinase
Leukemia inhibitory factor (LIF) signals via the heterodimeric receptor complex comprising the LIF receptor α subunit (LIFRα) and the common signal transducing subunit for interleukin-6 cytokine receptors, gp130. This study demonstrates that in different cell types, the level of LIFRα decreases d...
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Published in | The Journal of biological chemistry Vol. 275; no. 37; pp. 28793 - 28801 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
15.09.2000
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Subjects | |
Online Access | Get full text |
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Summary: | Leukemia inhibitory factor (LIF) signals via the heterodimeric receptor complex comprising the LIF receptor α subunit (LIFRα)
and the common signal transducing subunit for interleukin-6 cytokine receptors, gp130. This study demonstrates that in different
cell types, the level of LIFRα decreases during treatment with LIF or the closely related cytokine oncostatin M (OSM). Moreover,
insulin and epidermal growth factor induce a similar LIFRα down-regulation. The regulated loss of LIFRα is specific since
neither gp130 nor OSM receptor β shows a comparable change in turnover. LIFRα down-regulation correlates with reduced cell
responsiveness to LIF. Using protein kinase inhibitors and point mutations in LIFRα, we demonstrate that LIFRα down-regulation
depends on activation of extracellular signal-regulated kinase 1/2 and phosphorylation of the cytoplasmic domain of LIFRα
at serine 185. This modification appears to promote the endosomal/lysosomal pathway of the LIFRα. These results suggest that
extracellular signal-regulated kinase-activating factors like OSM and growth factors have the potential to lower specifically
LIF responsiveness in vivo by regulating LIFRα half-life. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M003986200 |