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Published on: June 15, 2017
Compartmentalized Ras signaling differentially contributes to phenotypic outputs.
1Department of Cellular and Molecular Physiology, Institute of Translational Research, University of Liverpool, Liverpool L69 3BX, UK.
Cellular Signalling
|May 28, 2013
Summary
Intracellular Ras proteins, crucial for cell signaling, can function effectively in various cellular compartments, not just the cell surface. This research shows that Golgi-localized Ras is as potent as N-Ras in supporting cell growth and transformation.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Ras proteins are key regulators of cellular signaling pathways.
- Their localization to the plasma membrane is well-established, but the role of intracellular Ras pools remains debated.
- Understanding Ras localization is critical for deciphering its diverse cellular functions.
Purpose of the Study:
- To investigate the functional capacity of Ras proteins in different subcellular compartments.
- To compare the ability of ER, Golgi, mitochondria, and endosomal Ras pools to support Ras activity.
- To determine if intracellular Ras localization influences proliferation and transformation.
Main Methods:
- Generation of Ras chimeras to target Ras isoforms to specific organelles (ER, Golgi, mitochondria, endosomes).
- Assay of MAP kinase and Akt pathway regulation by localized Ras.
- Assessment of cell proliferation and transformation driven by organelle-localized Ras.
Main Results:
- All tested intracellular locations (ER, Golgi, mitochondria, endosomes) supported Ras activity in regulating MAP kinase and Akt pathways.
- Endomembranous Ras pools demonstrated location-specific effects on proliferation and transformation.
- Ras localized to the Golgi exhibited potency comparable to N-Ras at the plasma membrane.
Conclusions:
- Intracellular Ras pools are functionally competent and can regulate key signaling pathways.
- Specific endomembranous localizations of Ras influence cellular outcomes like proliferation and transformation.
- The Golgi compartment is a significant site for Ras activity, supporting functions equivalent to plasma membrane-localized Ras.
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