Specific cancer associated mutations in the switch III-region of Ras increase tumorigenicity by nanocluster augmentation
- Åbo Akademi University, Finland
- University of Helsinki, Finland
- University of Texas Health Science Center at Houston, United States
- University of Turku, Finland
Abstract
Hotspot mutations of Ras drive cell transformation and tumorigenesis. Less frequent mutations in Ras are poorly characterized for their oncogenic potential. Yet insight into their mechanism of action may point to novel opportunities to target Ras. Here we show that several cancer-associated mutations in the switch III region moderately increase Ras activity in all isoforms. Mutants are biochemically inconspicuous, while their clustering into nanoscale signaling complexes on the plasma membrane, termed nanocluster, is augmented. Nanoclustering dictates downstream effector recruitment, MAPK-activity and tumorigenic cell proliferation. Our results describe an unprecedented mechanism of signaling protein activation in cancer.
Article and author information
Author details
Reviewing Editor
- Jonathan A Cooper, Fred Hutchinson Cancer Research Center, United States
Version history
- Received: May 21, 2015
- Accepted: August 13, 2015
- Accepted Manuscript published: August 14, 2015 (version 1)
- Version of Record published: September 11, 2015 (version 2)
Copyright
© 2015, Solman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Specific cancer associated mutations in the switch III-region of Ras increase tumorigenicity by nanocluster augmentation
eLife 4:e08905.
https://doi.org/10.7554/eLife.08905
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