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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
2000-10-13
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pubmed:abstractText |
Leukemia inhibitory factor (LIF) signals via the heterodimeric receptor complex comprising the LIF receptor alpha subunit (LIFRalpha) and the common signal transducing subunit for interleukin-6 cytokine receptors, gp130. This study demonstrates that in different cell types, the level of LIFRalpha decreases during treatment with LIF or the closely related cytokine oncostatin M (OSM). Moreover, insulin and epidermal growth factor induce a similar LIFRalpha down-regulation. The regulated loss of LIFRalpha is specific since neither gp130 nor OSM receptor beta shows a comparable change in turnover. LIFRalpha down-regulation correlates with reduced cell responsiveness to LIF. Using protein kinase inhibitors and point mutations in LIFRalpha, we demonstrate that LIFRalpha down-regulation depends on activation of extracellular signal-regulated kinase 1/2 and phosphorylation of the cytoplasmic domain of LIFRalpha at serine 185. This modification appears to promote the endosomal/lysosomal pathway of the LIFRalpha. 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 LIFRalpha half-life.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/LIF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/LIFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Leukemia Inhibitory Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Leukemia Inhibitory Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Lif protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lifr protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lifr protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, OSM-LIF
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28793-801
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10858440-3T3 Cells,
pubmed-meshheading:10858440-Amino Acid Motifs,
pubmed-meshheading:10858440-Animals,
pubmed-meshheading:10858440-Down-Regulation,
pubmed-meshheading:10858440-Endocytosis,
pubmed-meshheading:10858440-Enzyme Activation,
pubmed-meshheading:10858440-Growth Inhibitors,
pubmed-meshheading:10858440-HeLa Cells,
pubmed-meshheading:10858440-Humans,
pubmed-meshheading:10858440-Interleukin-6,
pubmed-meshheading:10858440-Leukemia Inhibitory Factor,
pubmed-meshheading:10858440-Leukemia Inhibitory Factor Receptor alpha Subunit,
pubmed-meshheading:10858440-Liver Neoplasms,
pubmed-meshheading:10858440-Lymphokines,
pubmed-meshheading:10858440-Lysosomes,
pubmed-meshheading:10858440-Mice,
pubmed-meshheading:10858440-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:10858440-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:10858440-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10858440-Rats,
pubmed-meshheading:10858440-Receptors, Cytokine,
pubmed-meshheading:10858440-Receptors, OSM-LIF
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pubmed:year |
2000
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pubmed:articleTitle |
Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase.
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pubmed:affiliation |
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, INSERM U463, France. frederic.blanchard@roswellpark.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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