We inhibited MKK7 in human neurons by CRISPR or activated it by overexpression (Fig. 3B, S2J). Neither manipulation impaired the ApoE3-induced increase in DLK levels, but both dramatically altered ApoE3-dependent downstream ERK1/2 phosphorylation. MKK7 CRISPR suppressed baseline ERK1/2 phosphorylation and blocked ApoE3-induced ERK1/2 phosphorylation, whereas MKK7 overexpression constitutively enhanced ERK1/2 phosphorylation and rendered it ApoE3-independent (Fig. 3B). Thus, DLK-mediated MKK7 phosphorylation mediates ERK1/2 phosphorylation in human neurons.
