RAF

null RAF kinases — ARAF, BRAF, and CRAF (RAF1) — are the MAP3K relay of the RAS-RAF-MEK-ERK cascade in the TKL group. RAS-GTP recruitment to the plasma membrane, dimerization, and phosphorylation events switch them on, after which RAFs phosphorylate MEK1/2 activation-loop serines. BRAF has the highest basal activity, and its V600E mutation drives melanoma, papillary thyroid cancer, and hairy-cell leukemia, motivating vemurafenib-class inhibitors; CRAF mutations underlie Noonan and LEOPARD syndromes. RAF dimerization also explains paradoxical ERK activation by first-generation inhibitors. Recombinant RAF proteins are central reagents for oncology kinase assays and resistance-mechanism studies.