Figure 2.

Two hypothetical modes of RET interaction/stimulation by GFL/GFRA. The extracellular domain of RET tyrosine kinase binds with GFL/GFRA which is linked to the plasma membrane via a glycosyl phosphatidylinositol (GPI) anchor. The interaction of RET with GFL/GFRA leads to the phosphorylation of tyrosine residues located in intracellular domain of RET and activates downstream signaling pathways. (A) GFL dimer binds to the GPI-anchored GFRA in lipid rafts and recruits RET; (B) GFRA without ligand forms a complex with RET that can serve as a receptor for GFL dimer.