BRAF

BRAF is a serine/threonine kinase immediately downstream of KRAS in the MAPK cascade, and the carrier of the most common activating kinase mutation in melanoma.

Function

BRAF is one of three RAF kinases. Activated RAS recruits BRAF to the membrane, where it dimerizes and phosphorylates MEK, which phosphorylates ERK; ERK then drives the transcriptional program of proliferation. BRAF depends on RAS for activation, but its position one step downstream makes it accessible to ATP-competitive inhibitors.

In cancer

The V600E mutation — a single glutamate-for-valine substitution in the activation loop — occurs in about half of melanomas, most hairy cell leukemias, and a large share of papillary thyroid