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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5124| Title: | Transcriptomal profiling of site-specific Ras signals |
| Keywords: | Ras Compartmentalization Gene microarrays Transformation |
| Publisher: | Elsevier |
| Description: | El pdf del artículo es el manuscrito de autor. Ras 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. PC’s work is supported by grants from the Spanish Ministry of Education and Science (MES) (BFU2005-00777 and GEN2003-20239-C06-03), the EU Sixth Framework Program under the SIMAP project, and the Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD06/0020/0105). Fondo de Investigaciones Sanitarias (FIS), Carlos III Institute, Spanish Ministry of Health. XRB’s work is supported by grants from the US National Cancer Institute/NIH (5R01-CA73735-10), the MES (SAF2006-01789 and GEN2003-20239-C06-01), the Castilla-León Autonomous Government (SA053A05), and the RTICC (RD06/0020/0001). F.N. was partially supported by a fellowship by the Ernst Schering Foundation. LA, FC, and IMB are Spanish Ministry of Education predoctoral fellows. All Spanish funding is co-sponsored by the European Union. Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5124 |
| Other Identifiers: | Cellular Signalling 19(11): 2264–2276 (2007) 0898-6568 http://hdl.handle.net/10261/5124 10.1016/j.cellsig.2007.06.025 |
| Appears in Collections: | Digital Csic |
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