Figure 1.

Representation of the RET receptor, its ligands and coreceptors and its activation mechanism. Inside the circle: RET is represented together with the soluble ligands glial derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN) and persephin (PSPN) and the coreceptors GFRα1-4 anchored to the membrane by glycosylphosphatidylinositol (GPI) domains. The full arrows indicate the principal interactions, while the broken ones indicate possible interactions. Outside the circle: activation of RET. Upon ligand-coreceptor interaction, the complex binds RET, leading to its dimerization and activation through tyrosine auto-phosphorylation. Six tyrosine residues in the intracellular part of the receptor, involved in its activation, are represented by orange dots and the three principal isoforms of RET are indicated as RET9, RET43, and RET51