Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition.

ABSTRACT: As a central element within the RAS/ERK pathway, the serine/threonine kinase BRAF plays a key role in development and homeostasis and represents the most frequently mutated kinase in tumors. Consequently, it has emerged as an important therapeutic target in various malignancies. Nevertheless, the BRAF activation cycle still raises many mechanistic questions as illustrated by the paradoxical action and side effects of RAF inhibitors. By applying SEC-PCP-SILAC, we analyzed protein-protein interactions of hyperactive BRAF^V600E and wild-type BRAF (BRAF^WT). We identified two macromolecular, cytosolic BRAF complexes of distinct molecular composition and phosphorylation status. Hyperactive BRAF^V600E resides in large complexes of higher molecu

SUBMITTER: Diedrich B 

PROVIDER: S-EPMC5331759 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature