Figure 6. The c-Met, PI3K, Akt, and c-Src pathway is involved in HGF-induced AP-1 activation.

(A&B) Primary osteoblasts were transfected with the AP-1-luciferase expression vector and then pretreated with c-Met inhibitor, Ly294002, Akt inhibitor, and PP2 or cotransfected with c-Met and c-Jun siRNA or p85, Akt and c-Src mutant before incubation with HGF for 24 h. Luciferase activity was then assayed (n = 4). *: p<0.05 as compared with HGF-treated group. (C) Schematic diagram of the signaling pathways involved in HGF-induced OPN expression in osteoblasts. HGF increases OPN expression by binding to the c-Met receptor and activating PI3K, Akt, and c-Src, which enhances binding of c-Jun to the AP-1 site. This results in the transactivation of OPN expression.