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.

过度的RTK信号传导，通常由Ras、Raf及/或MEK激活突变引起，在大多数人类肿瘤中均有发生。令人好奇的是，尚未报道下游效应激酶ERK中已确认的致癌驱动突变。为检验激活的ERK突变体是否能够充当癌蛋白，我们将最初在酵母ERK中发现的激活突变引入到单个果蝇ERK中。我们发现，此突变使ERK在独立于上游信号传导的情况下具有催化活性，并且其表达在体内诱导了广泛的过度增殖和增生性肿瘤形成。因此，在患者来源的肿瘤中鉴定出的一些人类ERK1/2突变实际上可能代表了被忽视的致癌性、致肿瘤突变。