Both ERK and PI3K contribute to the degranulation of skin MCs stimulated by MRGPRX2 or FcεRI. (A–C) Cultured and (D–F) ex vivo skin MCs were pretreated with inhibitors targeting ERK1 and ERK2 indiscriminately (SCH772984, 10 µM), ERK2 only (Vx-11e, 2 µM), JNK (SP600125, 5 µM), or PI3K (Pictilisib, 5 µM). β-hexosaminidase release stimulated by c48/80 (10 µg/mL), SP (30 µM) or IgER-cross-linking (CL) (by AER-37 antibody for cultured MCs at 0.1 µg/mL; by anti-FcεRIα-Ab 29C6 for ex vivo MCs at 0.5 µg/mL) was determined. The data are from 7–11 independent experiments, ns: not significant, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. skMCs: skin mast cells.