Activation of the MAPK pathway coupled with activation of the AKT signaling pathway is directly relevant to human melanoma: loss of PTEN is commonly associated with activating BRAF mutations in human melanoma, and genetics in mouse and zebrafish reveal that PTEN mutations are required for BRAFV600E mutations to progress from nevi to melanoma (Dankort et al., 2009; J. Richardson, J. den Hertog, E.E.P. unpublished data). Here, BRAF is linked to melanoma.