Signaling pathways mediate the neuroprotective effects of GDNF.
We show that the glial cell line-derived neurotrophic factor (GDNF) activates the PI3K/Akt-signaling pathway in human neuroblastoma cells that express functional Ret-receptor complexes. Consistent with this finding we show PI3K-dependent Bad-inactivation by binding to 14-3-3 proteins in response to GDNF. Using differential display techniques we detected several cDNA clones differentially expressed after treatment with GDNF or 6-OHDA.
Neff
F
F
Division of Neuropathology, Institute of Pathology, Munich Technical University, Munich, Germany. neff@neuropathologie-muenchen.de
Noelker
C
C
Eggert
K
K
Schlegel
J
J
D048948:14-3-3 Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D048948:14-3-3 Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006892:Hydroxydopamines; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C027802:5-hydroxydopamine; D014446:Tyrosine 3-Monooxygenase; D019869:Phosphatidylinositol 3-Kinases