Knock-in(g) RAF for a loop.

Phosphorylation of the activation loop in RAF kinases has been suggested to be critical for changes in activity. The extent to which the activation segment is phosphorylated, the specific structural consequences, and the relevance have however remained elusive. In this issue of the , Köhler (2015) addressed these questions by generating a mouse expressing a B‐Raf mutant with a non‐phosphorylatable activation loop. The mutant causes a range of developmental phenotypes; intriguingly, it also impairs the tumorigenic potential of a subset of BRAF mutants, suggesting potential new strategies for RAF inhibition.