A Structure is Worth a Thousand Words: New Insights for RAS and RAF Regulation.

The RAS GTPases are major drivers of tumorigenesis, and for RAS proteins to exert their full oncogenic potential, they must interact with the RAF kinases to initiate ERK cascade signaling. Although binding to RAS is typically a prerequisite for RAF to become an activated kinase, determining the molecular mechanisms by which this interaction results in RAF activation has been a challenging task. A major advance in understanding this process and RAF regulation has come from recent structural studies of various RAS and RAF multiprotein signaling complexes, revealing new avenues for drug discovery.