GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR SIGNALS THROUGH THE RET RECEPTOR AND ACTIVATES MITOGEN-ACTIVATED PROTEIN-KINASE

Glial cell line-derived neurotrophic factor (GDNF), a member of the tr ansforming growth factor-beta family of growth factors, was first iden tified by its ability to promote the survival of midbrain dopaminergic neurons in culture. We demonstrate that GDNF treatment of several neu roblastoma cell lines leads to dose-dependent tyrosine phosphorylation of the RET receptor and that other transforming growth factor-beta fa mily members are not able to activate the RET receptor. GDNF treatment of neuroblastoma cells also results in increased transcription of an Elk luciferase reporter gene, suggesting that GDNF activates the mitog en-activated protein kinase signal transduction pathway.