Glial cell-line derived neurotrophic factor receptor RET

RET (Rearranged during Transfection) is a receptor tyrosine kinase that serves as the main signaling receptor for glial cell line-derived neurotrophic factor (GDNF) and other GDNF family ligands (GFLs). It plays critical roles in neuronal survival, development, and maintenance, as well as in kidney morphogenesis and the enteric nervous system. Ligand binding occurs via a co-receptor complex: GDNF first binds to a glycosylphosphatidylinositol-linked co-receptor called GFRα1. The resulting complex then interacts with and activates the transmembrane tyrosine kinase activity of RET. Upon activation, intracellular signaling cascades are triggered—most notably: MAPK/ERK pathway, PI3K/AKT pathway, Src-family kinases pathway.

Other names

RETRearranged during Transfection

RET activation by GDNF supports the survival of dopaminergic and motor neurons, stimulates branching and proliferation of embryonic kidneys, and is crucial during development of the enteric nervous system. Small molecule agonists target RET for neuroprotective effects and modulation of glial activity.