Article
Allele-Specific Mechanisms of Activation of MEK1 Mutants Determine Their Properties.
Cancer discovery - 1 May 2018
Gao Yijun, Chang Matthew T, McKay Daniel, Na Na, Zhou Bing, Yaeger Rona, Torres Neilawattie M, Muniz Keven, Drosten Matthias, Barbacid Mariano, Caponigro Giordano, Stuart Darrin, Moebitz Henrik, Solit David B, Abdel-Wahab Omar, Taylor Barry S, Yao Zhan, Rosen Neal
Abstract excerpt
Mutations at multiple sites in MEK1 occur in cancer, suggesting that their mechanisms of activation might be different. We analyzed 17 tumor-associated MEK1 mutants and found that they drove ERK signaling autonomously or in a RAS/RAF-dependent manner. The latter are sensitive to feedback inhibition of RAF, which limits their functional output, and often cooccur with RAS or RAF mutations. They act as amplifiers of...
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