Firstly, ERK and ribosomal protein S6 kinase A (RSK), two downstream kinases of MAPK signaling, have been shown to phosphorylate and inhibit the upstream activator of AMPK, LKB1, and thereby block the activation of AMPK by LKB1 in BRAF(V600E)-driven melanoma [223] (Fig. 3a). This evidence concerns the gene MAPK1 and melanoma.