Figure 1: Mechanism of the ligand (GDNF, neurturin, artemin, persepin)- dependent activation of the ret receptor. The formation of a multimeric complex of the ret receptor with both a ligand and a GDNF-family co-receptor induces the dimerization of ret and its physiological activation. When an activating mutation (either point mutation or rearrangement) occurs the ret protein becomes constitutively activated undependently from the interaction with ligands and co-receptors.