MEK1/2 activity regulates the constitutive proteolysis of ApoER2 but is not involved in ApoER2 shedding induced by NGF. (A) PC12-ApoER2 cells were serum-starved and pre-treated with 10 μM DAPT and 25 μM PD98059 for 1 h. Then, the cells were incubated with 100 ng/mL NGF for 2 h. ApoER2 and the proteolytic control p75NTR were recognized by western blotting using antibodies directed against their intracellular regions. The activation of MEK1/2 by NGF was evidenced by recognition of phospho-ERK. α-tubulin is shown as a loading control. The blot levels of ApoER2 CTF (B) and p75NTR CTF (C) were normalized to the loading control α-tubulin and plotted as the average ± SD of three independent experiments. One way ANOVA, Holm-Sidak post-hoc test, *P < 0.05, **P < 0.01, ***P < 0.001, N.S, not significant.