Figure 1.

RET receptor structure, co-receptors, corresponding ligands and intracellular signaling pathway. RET activation is mediated by indirect interaction with one of four ligands: GDNF, ARTN, NRTN and PSPN linked to one of four GFRa1-4 co-receptors. The formation of the ligand/co-receptor/RET complex induces RET dimerization and triggers autophosphorylation at intracellular tyrosine residues leading the activation of downstream signaling pathways essential for cell growth, proliferation, survival, differentiation, or appetite control. The orange, light blue, blue and green arrows indicate the binding of adapter proteins. The light blue, blue, red, orange, green and violet lines indicate the activation of downstream signaling pathways. ARTN, Artemin; GDNF, glial cel-linederived neurotrophic factor; GFRa, GDNF family receptor-alfa; NRTN, Neurturin; PSPN, Persephin; RET, Rearranged during Transfection.