An in vitro BRAF activation assay elucidates molecular mechanisms driving disassembly of the autoinhibited BRAF state.

ABSTRACT: The RAF kinases (ARAF, BRAF, and CRAF) are essential components of the RAS-ERK signaling pathway, which controls vital cellular processes and is frequently dysregulated in human disease. Notably, mutations that alter BRAF function are prominent drivers of human cancer and certain RASopathy disorders, making BRAF an important target for therapeutic intervention. Despite extensive research, several aspects of BRAF regulation remain unclear. In this study, we developed an in vitro BRAF activation assay using purified autoinhibited BRAF:14-3-3₂:MEK complexes. Our results show that fully processed, active-state KRAS alone can promote dimer-dependent BRAF activation. Moreover, we found that phosphatidylserine (PS)-containing liposomes synergized with KRAS to promote BRAF activation, a

SUBMITTER: Ritt DA 

PROVIDER: S-EPMC12478067 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature