Fig. 6
From: Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy
Ezrin pathway. While in the dormant form, ezrin with N-terminal ezrin/radixin/moesin (ERM)-associated domain (N-ERMAD) associates in the cytoplasm with carboxy-ERMAD (C-ERMAD). Ezrin then becomes phosphorylated at various sites resulting in transformation to the active form. The C-terminal of transmembrane proteins as well as C-ERMAD binds with the N-terminal of activated ezrin. In addition, ezrin can serve as a linker protein between specific membranous proteins and F-actin via ERM-binding phosphoprotein 50 (EBP50). Guanosine diphosphate inhibitor (GDI) from the Rho-GDI complex is displaced by activated ezrin. This displacement can then stimulate PI4P5 kinase activity which is catalyzed by GDP/GTP exchange factor (GEF). Thereafter, PI4P5 kinase can act on PIP to convert PIP to phosphatidylinositol (4,5)-bisphosphate (PIP2). Thus, PIP2 sequentially converts dormant ezrin into the active form