title: Glial cell line-derived neurotrophic factor signals through the RET receptor and activates mitogen-activated protein kinase.
abstract: Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family of growth factors, was first identified by its ability to promote the survival of midbrain dopaminergic neurons in culture. We demonstrate that GDNF treatment of several neuroblastoma cell lines leads to dose-dependent tyrosine phosphorylation of the RET receptor and that other transforming growth factor-beta family 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 mitogen-activated protein kinase signal transduction pathway.
authors.affiliation: Department of Biological Chemistry, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0606, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Worby
authors.forename: Q C
authors.initials: QC
authors.lastname: Vega
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: H H
authors.initials: HH
authors.lastname: Chao
authors.forename: A F
authors.initials: AF
authors.lastname: Seasholtz
authors.forename: J E
authors.initials: JE
authors.lastname: Dixon
mesh_terms: D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004789:Enzyme Activation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009447:Neuroblastoma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D050807:ets-Domain Protein Elk-1
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D019000:Phosphotyrosine; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D017871:Calcium-Calmodulin-Dependent Protein Kinases