What is the RAS/MAPK pathway? The RAS/RAF/MEK/ERK pathway is the classical RAS/MAPK signaling pathway implicated in growth-factor mediated cell proliferation, differentiation and cell death [Malumbres and Barbacid 2003]. RAS activates RAF serine-threonine kinases including ARAF, BRAF and CRAF. Activated RAFs activate mitogen-activated protein kinase kinase 1/2 (MAP2K1/2 or MEK1/2) .MEK1 and MEK2 then phosphorylate their two known substrates, ERK1 and ERK2, products of MAPK3 and MAPK1 genes, respectively. References: Malumbres M, Barbacid M. Nat Rev Cancer. 6: 459-65, 2003. Aoki Y et al. Hum Mutat. 29: 992-1006, 2008