We found that ApoE3 stimulated MKK7 phosphorylation as strongly as ERK1/2 phosphorylation (~4–5 fold; Fig. 2G). DLK inhibition by knockdown or MBIP overexpression blocked ApoE3-stimulation of MKK7 and ERK1/2 phosphorylation. Conversely, DLK overexpression induced constitutive ERK1/2 and MKK7 phosphorylation, independent of ApoE3 (Fig. 2G). None of these manipulations increased JNK1/2/3 phosphorylation, used as a negative control. Knockdown of LZK (a.k.a. MAP3K13), another abundant MAP-kinase kinase kinase in neurons, also had no effect on ApoE3-induced increases in DLK protein and ERK1/2 phosphorylation (Fig. S2H, S2I).
