Figure 7. Model of MEK inhibitor-induced feedback on ERBB receptor signaling pathways.
In untreated cells EGFR is phosphorylated at T669 by MEK/ERK, which inhibits activation of EGFR and ERBB3. In the presence of AZD6244, ERK is inhibited and T669 phosphorylation is blocked, increasing EGFR and ERBB3 tyrosine phosphorylation and up-regulating downstream signaling.