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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
1997-6-23
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pubmed:abstractText |
The 120 kD product of the c-cbl oncogene is rapidly tyrosine phosphorylated and recruited to the EGF receptor following ligand binding. Cbl's oncogenic potential is activated by a large carboxy-terminal truncation that generated v-cbl and removes the Ring finger and proline-rich SH3-binding domains. Here we show that this truncation reveals a novel and highly conserved domain that can interact directly with the EGF receptor in a phosphorylation dependent manner. Furthermore we demonstrate that the v-cbl domain is not utilized by c-cbl for recruitment to the receptor since this binding property is not evident in c-cbl constructs with proline domain deletions, and it is only revealed following deletion of the Ring finger. We also analyse a loss-of-function mutation from the C. elegans homologue, sli-1, and show that the corresponding mutation in v-cbl ablates transformation and EGF receptor association. Thus our findings provide further evidence that v-cbl possesses a novel and evolutionarily conserved phosphotyrosine binding domain and that the dual capability of EGF receptor binding by cbl involves two distinct mechanisms. In addition these findings raise the possibility that v-cbl may transform by competing with c-cbl for phosphorylated binding sites on activated receptor complexes.
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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/Caenorhabditis elegans Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cbl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Helminth Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
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, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Retroviridae Proteins, Oncogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Sli-1 protein, C elegans,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2239-49
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9174060-3T3 Cells,
pubmed-meshheading:9174060-Amino Acid Sequence,
pubmed-meshheading:9174060-Animals,
pubmed-meshheading:9174060-Binding Sites,
pubmed-meshheading:9174060-Caenorhabditis elegans,
pubmed-meshheading:9174060-Caenorhabditis elegans Proteins,
pubmed-meshheading:9174060-Cell Transformation, Neoplastic,
pubmed-meshheading:9174060-Conserved Sequence,
pubmed-meshheading:9174060-Epidermal Growth Factor,
pubmed-meshheading:9174060-Helminth Proteins,
pubmed-meshheading:9174060-Mice,
pubmed-meshheading:9174060-Mutation,
pubmed-meshheading:9174060-Oncogene Protein v-cbl,
pubmed-meshheading:9174060-Phosphorylation,
pubmed-meshheading:9174060-Proline,
pubmed-meshheading:9174060-Proto-Oncogene Proteins,
pubmed-meshheading:9174060-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:9174060-Rabbits,
pubmed-meshheading:9174060-Receptor, Epidermal Growth Factor,
pubmed-meshheading:9174060-Retroviridae Proteins, Oncogenic,
pubmed-meshheading:9174060-Tyrosine,
pubmed-meshheading:9174060-Ubiquitin-Protein Ligases
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pubmed:year |
1997
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pubmed:articleTitle |
EGF receptor binding and transformation by v-cbl is ablated by the introduction of a loss-of-function mutation from the Caenorhabditis elegans sli-1 gene.
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pubmed:affiliation |
Department of Pathology, The University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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