Fig. 7
Signaling pathways contributing to mucus production. The CLCA1 (a Serpin) and 15-lipoxygenase-1-dependent pathways are triggered following the binding of IL-13 to its receptor. These pathways lead to the phosphorylation of STAT-6, leading to MUC5AC gene expression and mucus production. EGFR signaling is initiated following the activation of the PKC δ and PKC θ isoforms. The activation of EGFR kinase induces the Ras–Raf–MEK1/2–ERK1/2 pathway and the transcription of MUC5AC gene in airways via binding of the Sp1 transcription factor to specific binding sites within the gene promoter. Notch activates γ-secretase-mediated proteolytic processes, and Hes1 inhibits MUC5AC expression and mucus production
