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Transcriptomal profiling of site-specific Ras signals

AutorAgudo-Ibáñez, Lorena; Núñez, Fátima; Calvo, Fernando; Berenjeno, Inmaculada M.; Bustelo, Xosé R. ; Crespo, Piero
Palabras claveRas
Compartmentalization
Gene microarrays
Transformation
Fecha de publicaciónnov-2007
EditorElsevier
CitaciónCellular Signalling 19(11): 2264–2276 (2007)
ResumenRas proteins are distributed in distinct plasma-membrane microdomains and endomembranes. The biochemical signals generated by Ras therein differ qualitatively and quantitatively, but the extent to which this spatial variability impacts on the genetic program switched-on by Ras is unknown. We have used microarray technology to identify the transcriptional targets of localization-specific Ras subsignals in NIH3T3 cells expressing H-RasV12 selectively tethered to distinct cellular microenvironments. We report that the transcriptomes resulting from site-specific Ras activation show a significant overlap. However, distinct genetic signatures can also be found for each of the Ras subsignals. Our analyses unveil 121 genes uniquely regulated by Ras signals emanating from plasma-membrane microdomains. Interestingly, not a single gene is specifically controlled by lipid raft-anchored Ras. Furthermore, only 9 genes are exclusive for Ras signals from endomembranes. Also, we have identified 31 genes common to the site-specific Ras subsignals capable of inducing cellular transformation. Among these are the genes coding for Vitamin D receptor and for p120-GAP and we have assessed their impact in Ras-induced transformation. Overall, this report reveals the complexity and variability of the different genetic programs orchestrated by Ras from its main sublocalizations.
DescripciónEl pdf del artículo es el manuscrito de autor.
Versión del editorhttp://dx.doi.org/10.1016/j.cellsig.2007.06.025
URIhttp://hdl.handle.net/10261/5124
DOI10.1016/j.cellsig.2007.06.025
ISSN0898-6568
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