GDNF family receptors (provisional nomenclature, ENSFM00500000269996) 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 (Rearranged during transfection, ENSG00000165731). The endogenous ligands are typically dimeric, linked through disulphide bridges: glial cell-derived neurotrophic factor (GDNF, 211 aa, ENSG00000168621); neurturin (NRTN, 197 aa, ENSG00000171119); artemin (ARTN, 237 aa, ENSG00000117407) and PSPN (PSPN, 156 aa, ENSG00000125650).

Inhibitors of other receptor tyrosine kinases, such as semaxinib, which inhibits VEGF receptor function, may also inhibit Ret function [2]. 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.

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1. Klein, RD; Sherman, D; Ho, WH; Stone, D; Bennett, GL; Moffat, B; Vandlen, R; Simmons, L; Gu, Q; Hongo, JA; et al.. (1997) A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor. Nature, 387 (6634): 717-21. [PMID:9192898]

2. Mologni, L; Sala, E; Cazzaniga, S; Rostagno, R; Kuoni, T; Puttini, M; Bain, J; Cleris, L; Redaelli, S; Riva, B; et al.. (2006) Inhibition of RET tyrosine kinase by SU5416. J. Mol. Endocrinol., 37 (2): 199-212. [PMID:17032739]

3. Treanor, JJ; Goodman, L; de Sauvage, F; Stone, DM; Poulsen, KT; Beck, CD; Gray, C; Armanini, MP; Pollock, RA; Hefti, F; et al.. (1996) Characterization of a multicomponent receptor for GDNF. Nature, 382 (6586): 80-3. [PMID:8657309]