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Differential Activation of the Rac Pathway by Ha-Ras and K-Ras
Open accessAbstract
Ras proteins are key regulators of cell growth and differentiation. Mammalian cells express three closely related Ras proteins: Ha-Ras, K-Ras, and N-Ras. We have compared the abilities of the Ha-Ras and K-Ras isoforms to activate the Rac effector pathway, using three Rac-dependent readouts: induction of membrane ruffling and pinocytosis, stimulation of cell motility, and Pak binding. The total surface area of membrane ruffles induced by K-RasV12 was 2-fold greater than that induced by Ha-RasV12. Likewise, the number of K-RasV12-induced pinocytic vesicles per cell was approximately 2-fold greater than that induced by Ha-RasV12. In a wound healing assay, K-RasV12-injected cells migrated twice as fast as Ha-RasV12-injected cells. Moreover, the Pak binding activity of Rac, which is indicative of the amount of GTP-bound Rac, was higher in K-RasV12-expressing cells than Ha-RasV12-expressing cells. These results suggest that K-Ras activates Rac more efficiently than Ha-Ras. The preferential activation of Rac by K-Ras is dependent on the mode of membrane anchoring and impacts on the ability of K-Ras to regulate cell survival.
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Cites
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Increasing complexity of Ras signaling
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Induction of Membrane Ruffling and Fluid-Phase Pinocytosis in Quiescent Fibroblasts by ras Proteins
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Self-citationSpecific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain
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A Comprehensive Survey of Ras Mutations in Cancer
Prior, I. A., Lewis, P. D., & Mattos, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2612 · Cited by 2,063
Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Commisso, C., Davidson, S. M., Soydaner-Azeloglu, R. G., Parker, S. J., Kamphorst, J. J., Hackett, S., Grabocka, E., Nofal, M., Drebin, J. A., Thompson, C. B., et al. (2013) · Nature · doi:10.1038/nature12138 · Cited by 1,683
Self-citationMicroRNA: Biogenesis, Function and Role in Cancer
MacFarlane, L.-A., & R. Murphy, P. (2010) · Current Genomics · doi:10.2174/138920210793175895 · Cited by 1,584
Ras proteins: different signals from different locations
Hancock, J. F. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1105 · Cited by 756
Ras signalling on the endoplasmic reticulum and the Golgi
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Metadata
- Authors
- Walsh, A. B., & Bar-Sagi, D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 276
- Issue
- 19
- Pages
- 15609-15615
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2066505046
- Cited by
- 173
- References
- 4
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
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