RAF-MEK complex

The RAF-MEK complex refers to the physical and functional interaction between RAF kinase family members (ARAF, BRAF, CRAF/RAF1) and MEK kinases (MEK1/2), which is a critical step in the activation of the MAPK/ERK signaling pathway. RAF kinases phosphorylate and activate MEK kinases, which then phosphorylate ERK, promoting cellular outcomes such as proliferation, differentiation, and survival[4][5][6]. The complex formation is regulated by multiple factors—including RAS activity, scaffold proteins (such as KSR), 14-3-3 proteins, and specific post-translational modifications. Aberrant signaling through this complex, commonly due to oncogenic mutations in BRAF or other components, is a major driver of several cancers and is the direct target of multiple clinically approved kinase inhibitors[4][5][6]. Recent structural work has revealed the dynamic nature of these assemblies and how complex formation, autoinhibition, and activation are achieved and targeted pharmacologically[3][5][1][2]. However, because "RAF-MEK complex" designates an assembly rather than a single druggable receptor, the preferred nomenclature is precise (e.g., "BRAF kinase" or "MEK1 kinase"), and it is more informative to consider the individual components and their regulatory context.

Other names

RAF-MEK signaling complexBRAF-MEK complexCRAF-MEK complexRAF-MEK-ERK pathway components

Kinase inhibition (drugs block enzymatic activity of RAF or MEK, prevent phosphorylation of downstream targets) Disruption of dimerization/complex formation (some drugs inhibit the ability of RAF to dimerize or interact with MEK, reducing pathway activation) Allosteric inhibition (certain compounds induce conformational states that block complex assembly or signaling)