Papain stimulates ERK and AKT pathway activation, whereas an intact PI3K pathway is required for IL-4 production. (A–D) Immunoblot analysis of pERK/ERK (A), pAKT/AKT and pSHIP-1/actin (B), pGSK3β/GSK3β (C), and pPLCγ1/PLCγ1 and pPLCγ2/PLCγ2 (D) was prepared from BALB/c BMBs stimulated with papain or IgE cross-linking for the times (in minutes) noted. Protein lysates were sonicated before nuclei were removed in D. P, papain. IB, immunoblot. (E–G) IL-4 production by BMBs prestimulated for 30 min with general PI3K inhibitor Wortmannin (E), PI3K-isoform–specific inhibitors (PI3K p110β inhibitor TGX-221 and PI3K p110δ inhibitor IC87114) (F), or the MEK inhibitor PD98059 (G) and subsequently stimulated as indicated for 6 h. Data are representative of at least three similar experiments.