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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2002-8-23
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pubmed:abstractText |
We have previously demonstrated that cellular stimulation with GH results in the formation of a multiprotein signaling complex. One component of this multiprotein signaling complex is the adapter molecule c-Cbl. Here we have examined the role of c-Cbl in the mechanism of GH signal transduction. Forced expression of c-Cbl in NIH3T3 cells did not alter GH-stimulated Janus kinase 2 tyrosine phosphorylation nor GH-stimulated p44/42 MAPK activation and consequent Elk-1- mediated transcription. c-Cbl overexpression did, however, result in enhanced and prolonged GH-stimulated activation of phosphatidylinositol 3-kinase. Forced expression of c-Cbl did not affect GH-stimulated STAT5 tyrosine phosphorylation, nuclear translocation, nor binding to DNA but markedly abrogated GH-stimulated STAT5-mediated transactivation. c-Cbl overexpression resulted in increased ubiquitination and proteosomal degradation of STAT5 and increased degradation of GH-stimulated tyrosine phosphorylated STAT5. Cellular pretreatment with the proteosomal inhibitor MG132 reversed the effect of c-Cbl overexpression with prolonged duration of GH-stimulated STAT5 tyrosine phosphorylation and restoration of STAT5-mediated transcription. Thus, c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription by direction of STAT5 for proteosomal degradation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CBL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cbl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Human Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
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/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
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/Receptors, Somatotropin,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0013-7227
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
143
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3590-603
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12193575-3T3 Cells,
pubmed-meshheading:12193575-Animals,
pubmed-meshheading:12193575-Cell Nucleus,
pubmed-meshheading:12193575-Cysteine Endopeptidases,
pubmed-meshheading:12193575-Cysteine Proteinase Inhibitors,
pubmed-meshheading:12193575-DNA,
pubmed-meshheading:12193575-DNA-Binding Proteins,
pubmed-meshheading:12193575-Enzyme Activation,
pubmed-meshheading:12193575-Gene Expression Regulation,
pubmed-meshheading:12193575-Human Growth Hormone,
pubmed-meshheading:12193575-Janus Kinase 2,
pubmed-meshheading:12193575-Leupeptins,
pubmed-meshheading:12193575-Mice,
pubmed-meshheading:12193575-Milk Proteins,
pubmed-meshheading:12193575-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12193575-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12193575-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12193575-Multienzyme Complexes,
pubmed-meshheading:12193575-Phosphorylation,
pubmed-meshheading:12193575-Phosphotyrosine,
pubmed-meshheading:12193575-Proteasome Endopeptidase Complex,
pubmed-meshheading:12193575-Protein-Tyrosine Kinases,
pubmed-meshheading:12193575-Proto-Oncogene Proteins,
pubmed-meshheading:12193575-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:12193575-Receptors, Somatotropin,
pubmed-meshheading:12193575-STAT5 Transcription Factor,
pubmed-meshheading:12193575-Signal Transduction,
pubmed-meshheading:12193575-Trans-Activators,
pubmed-meshheading:12193575-Transcription, Genetic,
pubmed-meshheading:12193575-Transfection,
pubmed-meshheading:12193575-Ubiquitin,
pubmed-meshheading:12193575-Ubiquitin-Protein Ligases
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pubmed:year |
2002
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pubmed:articleTitle |
c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription.
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pubmed:affiliation |
Institute of Molecular and Cell Biology, National University of Singapore, Singapore 117609.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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