GDNF family receptors (provisional nomenclature) are extrinsic tyrosine kinase receptors. Ligand binding to the extracellular domain of the glycosylphosphatidylinositol-linked cell-surface receptors (tabulated below) activates a transmembrane tyrosine kinase enzyme, RET (see Receptor Tyrosine Kinases). The endogenous ligands are typically dimeric, linked through disulphide bridges: glial cell-derived neurotrophic factor GDNF (GDNF, P39905) (211 aa); neurturin (NRTN, Q99748) (197 aa); artemin (ARTN, Q5T4W7) (237 aa) and persephin (PSPN, O60542) (PSPN, 156 aa).

Inhibitors of other receptor tyrosine kinases, such as semaxanib, which inhibits VEGF receptor function, may also inhibit Ret function [6]. Mutations of RET and GDNF genes may be involved in Hirschsprung's disease, which is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction.

* Key recommended reading is highlighted with an asterisk

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* Merighi A. (2016) Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain. Expert Opin Ther Targets, 20 (2): 193-208. [PMID:26863504]

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