Supplemental Material for Kushnir et al., 2020

Excessive RTK signaling,
often caused by activating mutations in Ras, Raf and/or MEK, occurs in most
human tumors. Intriguingly, confirmed cancer-driver mutations in the downstream
effector kinase, ERK, have not been reported. To test if active ERK mutants can
function as oncoproteins, we introduced an activating mutation, originally identified in a yeast ERK, into the single Drosophila ERK. We find that this mutation
renders ERK catalytically active independently of upstream signaling, and that its expression induces extensive
over-proliferation and hyperplastic tumor formation in vivo. Thus, some human ERK1/2 mutations identified in
patient-derived tumours may actually represent overlooked oncogenic, cancer-causing
mutations.