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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
1994-11-10
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pubmed:abstractText |
Although previous studies have not identified transforming properties of the Ras-related protein R-Ras, two recent observations have prompted our further evaluation of R-Ras function. First, we observed that mutant forms of the closely related R-Ras2/TC21 protein (approximately 70% identity) exhibited the same potent transforming activity as oncogenic Ras proteins. Second, R-Ras association with Bcl-2 suggested a possible role for R-Ras in apoptotic growth control. Therefore, we have performed a detailed analysis of R-Ras transforming potential in NIH3T3 cells. Whereas expression of a mutant R-Ras protein (38V; analogous to the 12V activating Ras mutation) did not induce morphologic transformation of NIH3T3 cells, R-Ras(38V)-expressing cells proliferated in low serum, formed colonies in soft agar, and formed progressive tumors in nude mice. Like Ras-transformed cells, R-Ras(38V)-transformed cells exhibited constitutively activated mitogen activated protein kinases. Furthermore, R-Ras(38V) stimulated transcriptional activation of Ras-responsive promoter elements, and this activity (and transformation) was blocked by Raf dominant negative proteins. Finally, whereas co-expression of Bcl-2 did not cause significant alteration in wild type or mutant R-Ras transforming activity, coexpression of v-Myc and R-Ras(38V) induced a striking morphologic transformation of NIH3T3 cells. Taken together, these observations suggest that aberrant R-Ras function may stimulate malignant transformation, in the absence of morphologic transformation, via up-regulation of part of the Ras signal transduction pathway.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Rras protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:geneSymbol |
R-ras
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3281-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7936652-3T3 Cells,
pubmed-meshheading:7936652-Animals,
pubmed-meshheading:7936652-Cell Division,
pubmed-meshheading:7936652-Cell Transformation, Neoplastic,
pubmed-meshheading:7936652-GTP Phosphohydrolases,
pubmed-meshheading:7936652-Genes, myc,
pubmed-meshheading:7936652-Mice,
pubmed-meshheading:7936652-Protein-Tyrosine Kinases,
pubmed-meshheading:7936652-Proto-Oncogene Proteins,
pubmed-meshheading:7936652-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:7936652-Signal Transduction,
pubmed-meshheading:7936652-ras Proteins
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pubmed:year |
1994
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pubmed:articleTitle |
R-Ras induces malignant, but not morphologic, transformation of NIH3T3 cells.
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pubmed:affiliation |
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill 27599-7365.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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