As noted in Figure 5A, treatment of A375 cells with PLX4032 led to a rebound in pERK levels after 48 hrs, and to determine if this rebound level of pERK contributed to melanoma treatment resistance associated with PLX4032 treatment, we first knocked down pERK levels with the ERK shRNAs (which generate sustained and selectively knockdown of each pERK isoform (Figure 1A), and then added PLX4032. Here, MAPK1 is linked to melanoma.