Transcriptomal profiling of site-specific Ras signals.
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.
Agudo-Ibáñez
Lorena
L
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC), Departamento de Biología Molecular, Unidad de Biomedicina, CSIC-Universidad de Cantabria, Santander, Spain.
Núñez
Fátima
F
Calvo
Fernando
F
Berenjeno
Inmaculada M
IM
Bustelo
Xosé R
XR
Crespo
Piero
P
D000818:Animals; D002462:Cell Membrane / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D051379:Mice; D041681:NIH 3T3 Cells; D021381:Protein Transport; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism*
D018631:ras Proteins
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