RET binds GFRA4

Stable Identifier
R-HSA-8871227
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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). Early 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).

Literature References
PubMed ID Title Journal Year
9491986 Persephin, a novel neurotrophic factor related to GDNF and neurturin

Milbrandt, J, de Sauvage, FJ, Fahrner, TJ, Baloh, RH, Leitner, ML, Tansey, MG, Lampe, PA, Heuckeroth, RO, Kotzbauer, PT, Simburger, KS, Golden, JP, Davies, JA, Vejsada, R, Kato, AC, Hynes, M, Sherman, D, Nishimura, M, Wang, LC, Vandlen, R, Moffat, B, Klein, RD, Poulsen, K, Gray, C, Garces, A, Johnson, EM

Neuron 1998
Participants
Participant Of
hasEvent
Orthologous Events
Authored
Reviewed
Created