Analyses of the oncogenic BRAF^D594G variant reveal a kinase-independent function of BRAF in activating MAPK signaling.

ABSTRACT: Class 3 mutations in B-Raf proto-oncogene, Ser/Thr kinase (BRAF), that result in kinase-impaired or kinase-dead BRAF have the highest mutation frequency in BRAF gene in lung adenocarcinoma. Several studies have reported that kinase-dead BRAF variants amplify mitogen-activated protein kinase (MAPK) signaling by dimerizing with and activating WT C-Raf proto-oncogene, Ser/Thr kinase (CRAF). However, the structural and functional principles underlying their activation remain elusive. Herein, using cell biology and various biochemical approaches, we established that variant BRAF^D594G, a kinase-dead representative of class 3 mutation-derived BRAF variants, has a higher dimerization potential as compared with WT BRAF. Molecular dynamics simulations uncovered that t

SUBMITTER: Cope NJ 

PROVIDER: S-EPMC7039555 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature