The effects of clozapine on the GSK‐3‐mediated signaling pathway
- 4 February 2004
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 560 (1-3) , 115-119
- https://doi.org/10.1016/s0014-5793(04)00082-1
Abstract
We investigated the effect of 10 microM clozapine on the activity of glycogen synthase kinase-3beta (GSK-3beta) and its upstream and downstream molecules in SH-SY5Y human neuroblastoma cells. Clozapine activates both Akt- and Dvl-mediated phosphorylation of GSK-3beta through phosphorylation at Ser9, and increased total cellular and intranuclear levels of beta-catenin. Pretreatment with the specific inhibitor of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, LY294002 (20 microM), prevented the phosphorylation of Akt but did not affect the phosphorylation of GSK-3beta. These results suggest that clozapine regulates the phosphorylation of GSK-3beta through Wnt signal pathways involving Dvl upstream but not through the PI3K-Akt pathway in SH-SY5Y cells.Keywords
This publication has 19 references indexed in Scilit:
- Clozapine in Treatment-Resistant Patients With Schizophrenia, Schizoaffective Disorder, or Psychotic Bipolar DisorderThe Journal of Clinical Psychiatry, 2003
- Biphasic changes in the Ser-9 phosphorylation of glycogen synthase kinase-3β after electroconvulsive shock in the rat brainProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2003
- Regulation of Akt and glycogen synthase kinase-3β phosphorylation by sodium valproate and lithiumNeuropharmacology, 2002
- Characterisation of the phosphorylation of β-catenin at the GSK-3 priming site Ser45Biochemical and Biophysical Research Communications, 2002
- The renaissance of GSK3Nature Reviews Molecular Cell Biology, 2001
- The multifaceted roles of glycogen synthase kinase 3β in cellular signalingPublished by Elsevier ,2001
- Differential Regulation of Glycogen Synthase Kinase 3β by Insulin and Wnt SignalingJournal of Biological Chemistry, 2000
- Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3βPublished by Elsevier ,1998
- Clozapine in bipolar disorder: treatment implications for other atypical antipsychoticsJournal of Affective Disorders, 1998
- Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase BNature, 1995