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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
1999-8-31
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pubmed:abstractText |
Colony-stimulating factor-1 (CSF-1) activation of the CSF-1 receptor (CSF-1R) causes Cbl protooncoprotein tyrosine phosphorylation, Cbl-CSF-1R association and their simultaneous multiubiquitination at the plasma membrane. The CSF-1R is then rapidly internalized and degraded, whereas Cbl is deubiquitinated in the cytoplasm without being degraded. We have used primary macrophages from gene-targeted mice to study the role of Cbl. Cbl-/- macrophages form denser colonies and, at limiting CSF-1 concentrations, proliferate faster than Cbl+/+ macrophages. Their CSF-1Rs fail to exhibit multiubiquitination and a second wave of tyrosine phosphorylation previously suggested to be involved in preparation of the CSF-1-CSF-1R complex for endocytosis. Consistent with this result, Cbl-/- macrophage cell surface CSF-1-CSF-1R complexes are internalized more slowly, yet are still lysosomally degraded, and the CSF-1 utilization by Cbl-/- macrophages is reduced approximately 2-fold. Thus, attenuation of proliferation by Cbl is associated with its positive regulation of the coordinated multiubiquitination and endocytosis of the activated CSF-1R, and a reduction in the time that the CSF-1R signals from the cell surface. The results provide a paradigm for studies of the mechanisms underlying Cbl attenuation of proliferative responses induced by ligation of receptor tyrosine kinases.
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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/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Cbl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3616-28
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10393178-Animals,
pubmed-meshheading:10393178-Cell Division,
pubmed-meshheading:10393178-Cell Size,
pubmed-meshheading:10393178-Cell Survival,
pubmed-meshheading:10393178-Cell Transformation, Neoplastic,
pubmed-meshheading:10393178-Down-Regulation,
pubmed-meshheading:10393178-Endocytosis,
pubmed-meshheading:10393178-Gene Deletion,
pubmed-meshheading:10393178-Lysosomes,
pubmed-meshheading:10393178-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:10393178-Macrophages,
pubmed-meshheading:10393178-Mice,
pubmed-meshheading:10393178-Mice, Inbred C57BL,
pubmed-meshheading:10393178-Peptide Hydrolases,
pubmed-meshheading:10393178-Phosphorylation,
pubmed-meshheading:10393178-Proteasome Endopeptidase Complex,
pubmed-meshheading:10393178-Proto-Oncogene Proteins,
pubmed-meshheading:10393178-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:10393178-Receptor, Macrophage Colony-Stimulating Factor,
pubmed-meshheading:10393178-Signal Transduction,
pubmed-meshheading:10393178-Tyrosine,
pubmed-meshheading:10393178-Ubiquitin-Protein Ligases,
pubmed-meshheading:10393178-Ubiquitins,
pubmed-meshheading:10393178-ras Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation.
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pubmed:affiliation |
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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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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