title: Comparative proteomic analysis of compartmentalised Ras signalling.
abstract: Ras proteins are membrane bound signalling hubs that operate from both the cell surface and endomembrane compartments. However, the extent to which intracellular pools of Ras can contribute to cell signalling is debated. To address this, we have performed a global screen of compartmentalised Ras signalling. We find that whilst ER/Golgi- and endosomal-Ras only generate weak outputs, Ras localised to the mitochondria or Golgi significantly and distinctly influence both the abundance and phosphorylation of a wide range of proteins analysed. Our data reveal that ~80% of phosphosites exhibiting large (≥1.5-fold) changes compared to control can be modulated by organellar Ras signalling. The majority of compartmentalised Ras-specific responses are predicted to influence gene expression, RNA splicing and cell proliferation. Our analysis reinforces the concept that compartmentalisation influences Ras signalling and provides detailed insight into the widespread modulation of responses downstream of endomembranous Ras signalling.
authors.affiliation: Physiological Laboratory, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez-Valladares
authors.affiliation: Physiological Laboratory, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, United Kingdom.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Prior
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D018631:ras Proteins