14-3-3 protein–B-Raf complex

The **14-3-3 protein–B-Raf complex** is a dynamic protein–protein interaction critical for RAF kinase regulation in signal transduction pathways, including the MAPK/ERK pathway[1][2]. 14-3-3 proteins are dimeric adaptors that bind phosphorylated motifs on B-Raf, influencing its activation state: they can inhibit B-Raf by stabilizing an autoinhibited conformation when bound to specific phosphorylated serines, or promote activation and dimerization under other phosphorylation states[1][6]. This complex acts as a central node in growth factor and oncogenic signaling. Targeting this protein–protein interface is under investigation for cancer therapy, particularly given its role in MAPK pathway-driven tumors, but presents challenges due to the ubiquitous cellular roles of 14-3-3 proteins[1][6][2][5][7].

Other names

14-3-3:B-Raf complex14-3-3:RAF complexB-Raf:14-3-3 complexRAF kinase–14-3-3 complex

Inhibition of RAF kinase activity by preventing or destabilizing 14-3-3/B-Raf interaction Stabilization of autoinhibited B-Raf conformation by promoting 14-3-3 binding at inhibitory phospho-sites Inhibition of oncogenic B-Raf signaling by blockade of dimerization or membrane translocation