|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
49
|
|
pubmed:dateCreated |
2007-10-25
|
|
pubmed:abstractText |
Several distinct mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are associated with non-small cell lung cancer, but mechanisms underlying their oncogenic potential are incompletely understood. Although normally ligand-induced kinase activation targets EGFR to Cbl-mediated receptor ubiquitinylation and subsequent degradation in lysosomes, we report that certain EGFR mutants escape this regulation. Defective endocytosis characterizes a deletion mutant of EGFR, as well as a point mutant (L858R-EGFR), whose association with c-Cbl and ubiquitinylation are impaired. Our data raise the possibility that refractoriness of L858R-EGFR to downregulation is due to enhanced heterodimerization with the oncogene product HER2, which leads to persistent stimulation.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0950-9232
|
|
pubmed:author |
pubmed-author:Ben-BasatYY,
pubmed-author:BenjaminSS,
pubmed-author:CitriAA,
pubmed-author:CorsoSS,
pubmed-author:GayAA,
pubmed-author:GiordanoSS,
pubmed-author:KatzMM,
pubmed-author:KochupurakkalB SBS,
pubmed-author:LaviSS,
pubmed-author:PineyMM,
pubmed-author:ShtiegmanKK,
pubmed-author:StarrAA,
pubmed-author:VexlerAA,
pubmed-author:YardenYY,
pubmed-author:YosefR BRB,
pubmed-author:ZwangYY
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
25
|
|
pubmed:volume |
26
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
6968-78
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:17486068-Biotinylation,
pubmed-meshheading:17486068-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:17486068-Cell Line, Tumor,
pubmed-meshheading:17486068-Dimerization,
pubmed-meshheading:17486068-Down-Regulation,
pubmed-meshheading:17486068-Humans,
pubmed-meshheading:17486068-Immunoblotting,
pubmed-meshheading:17486068-Immunoprecipitation,
pubmed-meshheading:17486068-Lung Neoplasms,
pubmed-meshheading:17486068-Lysosomes,
pubmed-meshheading:17486068-Mutagenesis, Site-Directed,
pubmed-meshheading:17486068-Mutation,
pubmed-meshheading:17486068-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:17486068-Receptor, Epidermal Growth Factor,
pubmed-meshheading:17486068-Receptor, erbB-2,
pubmed-meshheading:17486068-STAT3 Transcription Factor,
pubmed-meshheading:17486068-Signal Transduction,
pubmed-meshheading:17486068-Transcription, Genetic,
pubmed-meshheading:17486068-Ubiquitin,
pubmed-meshheading:17486068-Ubiquitination
|
|
pubmed:year |
2007
|
|
pubmed:articleTitle |
Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling.
|
|
pubmed:affiliation |
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
