Journal
FEBS JOURNAL
Volume 276, Issue 7, Pages 1817-1825Publisher
WILEY
DOI: 10.1111/j.1742-4658.2009.06928.x
Keywords
compartmentalization; GTPase; isoforms; MAP kinase; microdomains; nanoclusters; Raf; Ras; receptor; scaffold
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Funding
- Royal Society University Research Fellow
- Cancer Research UK
- Wellcome Trust
- North West Cancer Research Fund.
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Differential subcellular compartmentalization of the three main Ras isoforms (H-Ras, N-Ras and K-Ras) is believed to underlie their biological differences. Modulatable interactions between cellular membranes and Ras C-terminal hypervariable region motifs determine differences in trafficking and the relative proportions of each isoform in cell-surface signalling nanoclusters and intracellular endoplasmic reticulum/Golgi, endosomal and mitochondrial compartments. Ras regulators, effectors and scaffolds are also differentially distributed, potentially enabling preferential coupling to specific signalling pathways in each subcellular location. Here we summarize the mechanisms underlying compartment-specific Ras signalling and the outputs generated.
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