The effects of clozapine on the GSK-3-mediated signaling pathway

We investigated the effect of 10 μM clozapine on the activity of glycogen synthase kinase-3β (GSK-3β) and its upstream and downstream molecules in SH-SY5Y human neuroblastoma cells. Clozapine activates both Akt- and Dvl-mediated phosphorylation of GSK-3β through phosphorylation at Ser9, and increase...

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Bibliographic Details
Published in:FEBS letters 2004-02, Vol.560 (1), p.115-119
Main Authors: Kang, Ung Gu, Seo, Myoung Suk, Roh, Myoung-Sun, Kim, Yeni, Yoon, Se Chang, Kim, Yong Sik
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
beta Catenin
Cell Division - drug effects
Cell Line, Tumor
Cell Nucleus - chemistry
Chromones - pharmacology
Clozapine
Clozapine - pharmacology
Culture Media, Serum-Free
Cytoskeletal Proteins - analysis
Cytoskeletal Proteins - drug effects
Dose-Response Relationship, Drug
Dvl
Dvl, dishevelled
Enzyme Inhibitors - pharmacology
Glycogen Synthase Kinase 3 - chemistry
Glycogen Synthase Kinase 3 - drug effects
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
Glycogen synthase kinase-3β
GSK-3β, glycogen synthase kinase-3β
Humans
Morpholines - pharmacology
Neuroblastoma - enzymology
Phosphatidylinositol 3-kinase
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
PI3K, phosphatidylinositol 3-kinase
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins - drug effects
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Serine - metabolism
Signal Transduction
Time Factors
Trans-Activators - analysis
Trans-Activators - drug effects
Wnt
Wnt Proteins
Zebrafish Proteins
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Summary:We investigated the effect of 10 μM clozapine on the activity of glycogen synthase kinase-3β (GSK-3β) and its upstream and downstream molecules in SH-SY5Y human neuroblastoma cells. Clozapine activates both Akt- and Dvl-mediated phosphorylation of GSK-3β through phosphorylation at Ser9, and increased total cellular and intranuclear levels of β-catenin. Pretreatment with the specific inhibitor of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, LY294002 (20 μM), prevented the phosphorylation of Akt but did not affect the phosphorylation of GSK-3β. These results suggest that clozapine regulates the phosphorylation of GSK-3β through Wnt signal pathways involving Dvl upstream but not through the PI3K-Akt pathway in SH-SY5Y cells.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(04)00082-1