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

Ung Gu Kang; Myoung Suk Seo; Myoung Sun Roh; Yeni Kim; Se Chang Yoon; Yong Sik Kim

doi:10.1016/S0014-5793(04)00082-1

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

Ung Gu Kang, Myoung Suk Seo, Myoung Sun Roh, Yeni Kim, Se Chang Yoon, Yong Sik Kim

Department of Medicine

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122 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	115-119
Number of pages	5
Journal	FEBS Letters
Volume	560
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(04)00082-1
State	Published - 27 Feb 2004

Keywords

Clozapine
Dvl
Glycogen synthase kinase-3β
Phosphatidylinositol 3-kinase
Wnt

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10.1016/S0014-5793(04)00082-1

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title = "The effects of clozapine on the GSK-3-mediated signaling pathway",

abstract = "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.",

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AU - Kang, Ung Gu

AU - Seo, Myoung Suk

AU - Roh, Myoung Sun

AU - Kim, Yeni

AU - Yoon, Se Chang

AU - Kim, Yong Sik

PY - 2004/2/27

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N2 - 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.

AB - 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.

KW - Clozapine

KW - Dvl

KW - Glycogen synthase kinase-3β

KW - Phosphatidylinositol 3-kinase

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

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Keywords

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