Activation of K-RAS by co-mutation of codons 19 and 20 is transforming
Adams, David J
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Naguib, A., Wilson, C., Adams, D. J., & Arends, M. (2011). Activation of K-RAS by co-mutation of codons 19 and 20 is transforming. https://doi.org/10.1186/1750-2187-6-2
Abstract The K-RAS oncogene is widely mutated in human cancers. Activating mutations in K-RAS give rise to constitutive signalling through the MAPK/ERK and PI3K/AKT pathways promoting increased cell division, reduced apoptosis and transformation. The majority of activating mutations in K-RAS are located in codons 12 and 13. In a human colorectal cancer we identified a novel K-RAS co-mutation that altered codons 19 and 20 resulting in transitions at both codons (L19F/T20A) in the same allele. Using focus forming transformation assays in vitro , we showed that co-mutation of L19F/T20A in K-RAS demonstrated intermediate transforming ability that was greater than that of individual L19F and T20A mutants, but less than that of G12D and G12V K-RAS mutants. This demonstrated the synergistic effects of co-mutation of codons 19 and 20 and illustrated that co-mutation of these codons is functionally significant.
External DOI: https://doi.org/10.1186/1750-2187-6-2
This record's URL: http://www.dspace.cam.ac.uk/handle/1810/237258
Rights Holder: Naguib et al.; licensee BioMed Central Ltd.