rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-9
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pubmed:abstractText |
RET/papillary thyroid carcinoma (PTC) oncoproteins result from the in-frame fusion of the RET receptor tyrosine kinase with protein dimerization motifs encoded by heterologous genes. Here, we show that RET/PTC1 activates the Rap1 small GTPase. The activation of Rap1 was dependent on the phosphorylation of RET Tyr(1062). RET/PTC1 recruited a complex containing growth factor receptor binding protein 2-associated binding protein 1 (Gab1), CrkII (v-crk sarcoma virus CT10 oncogene homologue II), and C3G (Rap guanine nucleotide exchange factor 1). By using dominant-negative and small interfering duplex (small interfering RNA) oligonucleotides, we show that RET/PTC1-mediated Rap1 activation was dependent on CrkII, C3G, and Gab1. Activation of Rap1 was involved in the RET/PTC1-mediated stimulation of the BRAF kinase and the p42/p44 mitogen-activated protein kinases. Proliferation and stress fiber formation of RET/PTC1-expressing PC Cl 3 thyroid follicular cells were inhibited by the dominant-negative Rap1(N17) and by Rap1-specific GTPase-activating protein. Thus, Rap1 is a downstream effector of RET/PTC and may contribute to the transformed phenotype of RET/PTC-expressing thyrocytes.
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/BRAF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GAB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Monomeric GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins B-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-crk,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/RET protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
381-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17210721-Actins,
pubmed-meshheading:17210721-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17210721-Carcinoma, Papillary,
pubmed-meshheading:17210721-Cell Growth Processes,
pubmed-meshheading:17210721-Cell Line, Tumor,
pubmed-meshheading:17210721-Humans,
pubmed-meshheading:17210721-Monomeric GTP-Binding Proteins,
pubmed-meshheading:17210721-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:17210721-Proto-Oncogene Proteins c-crk,
pubmed-meshheading:17210721-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:17210721-Signal Transduction,
pubmed-meshheading:17210721-Thyroid Neoplasms,
pubmed-meshheading:17210721-Transfection,
pubmed-meshheading:17210721-rap1 GTP-Binding Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase.
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pubmed:affiliation |
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR G. Salvatore, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita' Federico II, via Sergio Pansini 5, 8-131 Naples, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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