Figure 2

Positive and negative effects of GPC3 on cell signaling. In the Wnt signaling pathway (left), GPC3 exerts a positive effect. Wnt binds to the receptor Frizzled to induce signaling (green arrow). GPC3 facilitates and/or stabilizes the interaction between Wnt and Frizzled with the consequent increment on signaling. In the Hedgehog (Hh) signaling pathway (right), GPC3 exerts an inhibitory effect. The binding of Hh to the receptor Patched (Ptc) triggers the signaling pathway by blocking the inhibitory activity of Ptc on Smoothened. GPC3 competes with Ptc for Hh binding. The interaction of Hh with GPC3 triggers the endocytosis and degradation of the complex with the consequent reduction of Hh available for binding to Ptc.