Although the ERK1/2 and ERK5 pathways share greater than 50% sequence homology at the N-terminal domain, ERK1/2 and ERK5 have been shown to mediate differential responses to growth factors, hypoxia, and pharmacological targeting with rapidly accelerated fibrosarcoma (BRAF) and MEK1/2 inhibitors. This evidence concerns the gene MAPK3 and fibrosarcoma.