Article
BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition.
Cancer cell - 14 Sept 2015
Yao Zhan, Torres Neilawattie M, Tao Anthony, Gao Yijun, Luo Lusong, Li Qi, de Stanchina Elisa, Abdel-Wahab Omar, Solit David B, Poulikakos Poulikos I, Rosen Neal
Abstract excerpt
ERK signaling requires RAS-induced RAF dimerization and is limited by feedback. Activated BRAF mutants evade feedback inhibition of RAS by either of two mechanisms. BRAF V600 mutants are activated monomers when RAS activity is low; all other activating BRAF mutants function as constitutive RAS-independent dimers. RAF inhibitors effectively inhibit mutant monomers, but not dimers; their binding to one site in the...
Topics
- Cell Line, Tumor
- Dimerization
- Drug Resistance, Neoplasm
- Humans
- MAP Kinase Signaling System
- Mutation
- Protein Kinase Inhibitors
- Proto-Oncogene Proteins B-raf
- ras Proteins