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rdf:type |
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lifeskim:mentions |
umls-concept:C0015295,
umls-concept:C0205224,
umls-concept:C0679058,
umls-concept:C1514562,
umls-concept:C1517945,
umls-concept:C1547699,
umls-concept:C1622525,
umls-concept:C1879547,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C2700640
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pubmed:issue |
29
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pubmed:dateCreated |
1999-8-19
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pubmed:abstractText |
TPR-MET, a transforming counterpart of the c-MET proto-oncogene detected in experimental and human cancer, results from fusion of the MET kinase domain with a dimerization motif encoded by TPR. In this rearrangement the exons encoding the Met extracellular, transmembrane and juxtamembrane domains are lost. The juxtamembrane domain has been suggested to be a regulatory region endowed with negative feedback control. To understand whether its absence is critical for the generation of the Tpr-Met transforming potential, we produced a chimeric molecule (Tpr-juxtaMet) with a conserved juxtamembrane domain. The presence of the domain (aa 962-1009) strongly inhibited Tpr-Met dependent cell transformation. Cell proliferation, anchorage-independent growth, motility and invasion were also impaired. The enzymatic behavior of Tpr-Met and Tpr-juxtaMet was the same, while Tpr-juxtaMet ability to associate cytoplasmic signal transducers and to elicit downstream signaling was severely impaired. These data indicate that the presence of the juxtamembrane domain counterbalances the Tpr-Met transforming potential and therefore the loss of the exon encoding the juxtamembrane domain is crucial in the generation of the active TPR-MET oncogene.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/GAB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gab1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
22
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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 |
4275-81
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10435641-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10435641-Animals,
pubmed-meshheading:10435641-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10435641-Cell Line, Transformed,
pubmed-meshheading:10435641-Cell Transformation, Neoplastic,
pubmed-meshheading:10435641-DNA, Complementary,
pubmed-meshheading:10435641-Dimerization,
pubmed-meshheading:10435641-Enzyme Activation,
pubmed-meshheading:10435641-Exons,
pubmed-meshheading:10435641-Feedback,
pubmed-meshheading:10435641-Fibroblasts,
pubmed-meshheading:10435641-GRB2 Adaptor Protein,
pubmed-meshheading:10435641-Humans,
pubmed-meshheading:10435641-Leucine Zippers,
pubmed-meshheading:10435641-Oncogene Proteins, Fusion,
pubmed-meshheading:10435641-Phosphoproteins,
pubmed-meshheading:10435641-Phosphorylation,
pubmed-meshheading:10435641-Protein Processing, Post-Translational,
pubmed-meshheading:10435641-Protein Structure, Tertiary,
pubmed-meshheading:10435641-Proteins,
pubmed-meshheading:10435641-Rats,
pubmed-meshheading:10435641-Rats, Inbred F344,
pubmed-meshheading:10435641-Recombinant Fusion Proteins,
pubmed-meshheading:10435641-Sequence Deletion,
pubmed-meshheading:10435641-Signal Transduction,
pubmed-meshheading:10435641-Structure-Activity Relationship,
pubmed-meshheading:10435641-Transfection,
pubmed-meshheading:10435641-Tumor Stem Cell Assay
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pubmed:year |
1999
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pubmed:articleTitle |
Loss of the exon encoding the juxtamembrane domain is essential for the oncogenic activation of TPR-MET.
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pubmed:affiliation |
Institute for Cancer Research and Treatment (IRCC), University of Torino School of Medicine, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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