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Activating Ras Mutations in vitro and in Cancer
From Q-bio
Edward C. Stites, Paul C. Trampont, and Kodi Ravichandran
- Abstract
- Two classes of Ras mutations increase Ras activation and have in vitro transformation potential: GAP insensitive and fast-cycling Ras. While GAP insensitive mutants are commonly found in tumors, fast-cycling mutants are rarely found. It is unclear why fast-cycling mutants are not more prevalent in cancer. Our quantitative model of the oncogenic Ras signaling module predicts differential Ras activation in a manner dependent upon expression level and mutant class. Quantitative, single-cell experiments confirm the predicted patterns of Ras pathway activation. These results suggest that spontaneous fast-cycling mutations fail to cause cancer as they induce a comparably small increase in Ras activation.
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