RET is a receptor tyrosine kinase with a cadherin-related motif and a cysteine-rich domain in the extracellular domain (Takahashi et al. 1988). It is the receptor for members of the glial cell-derived neurotrophic factor (GDNF) family of ligands (Lin et al. 1993, Kotzbauer et al. 1996, Baloh et al. 1998, Milbrandt et al. 1998). RET can only bind these ligands in the presence of a co-receptor from the family of glycosylphosphatidylinositol (GPI)-anchored co-receptors collectively termed GDNF family receptor-alpha (GFRA) (Treanor et al. 1996, Jing et al. 1996, Plaza-Menacho et al. 2006). Earlier models proposed that GDNF formed a complex with GFRA1 and subsequently recruited RET (Massagué et al. 1996). Current models suggest that GFRA and RET preassociate before ligand binding, based on binding and site-directed mutagenesis studies (Eketjäll et al. 1999, Cik et al. 2000). An alternative model suggests that GPI-anchored GFRA recruits RET to lipid rafts after GDNF stimulation (Tansey et al. 2000). The stoichiometry as well as the kinetics of ligand-receptor complex formation are not well understood. It is believed that all GDNF family members interact with their cognate co-receptor and activate RET in a similar manner to GDNF (Airaksinen & Saarma 2002).
Lampe, PA, Johnson, EM, Heuckeroth, RO, Milbrandt, J, Osborne, PA, Creedon, DJ, Fahrner, TJ, Baloh, RH, Tansey, MG
Enomoto, H, Lampe, PA, Simburger, KS, Johnson, EM, Milbrandt, J, Fahrner, TJ, Tansey, MG, Baloh, RH, Araki, T, Leitner, ML
Antonio, L, Luo, Y, Altrock, BW, Jing, S, Hu, S, Wen, D, Holst, PL, Cupples, R, Tamir, R, Fang, M, Hu, Z, Yu, Y, Fox, GM, Louis, JC
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