Analysis shows GDNF family receptors activate RET signaling in response to GDNF family ligands and GDF15.
GDNF family receptors (GFR) are extrinsic co-receptors, where ligand binding to the extracellular domain of the glycosylphosphatidylinositol-linked cell-surface GFRs activates a transmembrane tyrosine kinase enzyme, RET. The endogenous ligands are typically dimeric, linked through disulphide bridges: glial cell-derived neurotrophic factor GDNF (211 aa); neurturin (197 aa); artemin (237 aa) and persephin (156 aa), referred to as GDNF family ligands (GFLs). There is evidence for RET-dependent and RET-independent signalling [5]. Growth/Differentiation Factor 15 (GDF15) has been shown to activate GFRAL, a transmembrane protein that similarly forms a complex with RET [8, 10].
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Chloe J. Peach (2025) studied this question.
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