In 28% of melanomas, NRAS is mutated in one of two hotspots: G12 or Q61. Phosphoproteomic analysis of primary human melanocytes transduced with G12 and Q61 showed different phosphorylation events in the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Surprisingly, NRAS(G12) modulates the PI3K pathway and overexpresses the kinase PIM2, whereas NRAS(Q61) is associated with the MAPK pathway and overexpression of CK2α.
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