Figure 8. Involvement of ERK and PKC signaling in afatinib amplification of secretion.

(A) Schematic of proposed mechanism of TKI action. EGF binding to its receptor (EGFR) inhibits activation of basolateral K⁺ channels and apical Cl^– channels via PKC and ERK signaling. TKI abolishes this inhibition. (B) (Left) short-circuit current in T84 cells showing responses to afatinib (20 μM), PKC inhibitor (Ro-31-8220, 10 μM), ERK inhibitor (GDC-0994, 10 μM), alone or together, added 25 minutes before 100 μM carbachol. (Right) summary of peak carbachol-induced current (mean ± SEM, n = 4–14). **P < 0.01, by 2-tailed t test.