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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1995-9-25
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pubmed:abstractText |
We have introduced three Hirschsprung (HSCR) mutations localized in the tyrosine kinase domain of RET into the RET/PTC2 chimaeric oncogene which is capable of transforming NIH3T3 mouse fibroblasts and of differentiating pC12 rat pheochromocytoma cells. The three HSCR mutations abolished the biological activity of RET/PTC2 in both cell types and significantly decreased its tyrosine phosphorylation. By contrast, a rare polymorphism in exon 18 does not alter the transforming capability of RET/PTC2 or its tyrosine phosphorylation. These data suggest a loss of function effect of HSCR mutations which might act through a dominant negative mechanism. Our model system is therefore capable of discriminating between causative HSCR mutations and rare polymorphisms in the tyrosine kinase domain of RET.
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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/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ret oncogene protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Ret protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ret protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1061-4036
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
35-40
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7647787-3T3 Cells,
pubmed-meshheading:7647787-Animals,
pubmed-meshheading:7647787-Base Sequence,
pubmed-meshheading:7647787-Cell Differentiation,
pubmed-meshheading:7647787-Cell Transformation, Neoplastic,
pubmed-meshheading:7647787-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:7647787-Drosophila Proteins,
pubmed-meshheading:7647787-Exons,
pubmed-meshheading:7647787-Genetic Complementation Test,
pubmed-meshheading:7647787-HeLa Cells,
pubmed-meshheading:7647787-Hirschsprung Disease,
pubmed-meshheading:7647787-Humans,
pubmed-meshheading:7647787-Mice,
pubmed-meshheading:7647787-Molecular Sequence Data,
pubmed-meshheading:7647787-Mutagenesis, Site-Directed,
pubmed-meshheading:7647787-Mutation,
pubmed-meshheading:7647787-PC12 Cells,
pubmed-meshheading:7647787-Phosphorylation,
pubmed-meshheading:7647787-Precipitin Tests,
pubmed-meshheading:7647787-Proto-Oncogene Proteins,
pubmed-meshheading:7647787-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:7647787-Rats,
pubmed-meshheading:7647787-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:7647787-Recombinant Fusion Proteins,
pubmed-meshheading:7647787-Transfection,
pubmed-meshheading:7647787-Tyrosine
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pubmed:year |
1995
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pubmed:articleTitle |
Loss of function effect of RET mutations causing Hirschsprung disease.
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pubmed:affiliation |
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova Quarto, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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