SILAC analysis of compartmentalised Ras signalling

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We are interested in Ras proteins that sit near the top of many cell signalling pathways and control key cellular functions such as proliferation, migration and cell death. Cells contain three almost identical versions (isoforms) that differ only in their preferred locations within the cell. These overlapping localisations are believed to underlie the biological differences known to exist between the isoforms. This model suggests that by operating from different platforms within the cell, Ras isoforms will come into contact with distinct pools of activators and downstream signalling proteins. We plan to test this model by targetting Ras to each of the different organelles where it is known to reside and compare the signals that are produced. We will use new technology that enables the responses of networks containing thousands of proteins to be precisely analysed. Our datasets will be mined to reveal likely relationships between signalling from each compartment and functional outputs that will be confirmed using cell-based assays. Together these data will provide a comprehensive picture of compartment-specific signalling.