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Membrane depolarization induces the undulating phosphorylation/dephosphorylation of glycogen synthase kinase 3beta, and this dephosphorylation involves protein phosphatases 2A and 2B in SH-SY5Y human neuroblastoma cells
Cited 52 time in
Web of Science
Cited 51 time in Scopus
- Authors
- Issue Date
- 2005-04-01
- Citation
- J Biol Chem. 280(23), 22044-22052
- Keywords
- Androstadienes/pharmacology ; Animals ; Calcineurin/*chemistry ; Calcium/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Membrane/*metabolism ; Enzyme Inhibitors/pharmacology ; Glioblastoma/metabolism ; Glycogen Synthase Kinase 3/*metabolism ; Hippocampus/cytology/metabolism ; Humans ; Immunoblotting ; Immunoprecipitation ; Microscopy, Confocal ; Naphthalenes/pharmacology ; PC12 Cells ; Phosphoprotein Phosphatases/*chemistry ; Phosphorylation ; Potassium Chloride/pharmacology ; Rats ; Serine/chemistry ; Threonine/chemistry ; Time Factors ; Transfection
- Abstract
- Changes in plasma membrane electrical potential evoke signals that regulate the expressions of various genes in the nervous system. However, the role of glycogen synthase kinase 3beta (GSK-3beta) in this process has not been elucidated. Thus, this study was performed to examine whether membrane depolarization can regulate the phosphorylation of GSK-3beta and to identify the molecular mechanisms involved in this regulation. The depolarization by treating with 100 mm KCl for 5 min resulted in the undulating phosphorylation of GSK-3beta at Ser-9 in SH-SY5Y human neuroblastoma cells, in H19 -7/IGF-IR rat embryonic hippocampal cells, and in PC12 rat pheochromocytoma cells, but not in A172 human glioblastoma cells. Cellular beta-catenin contents showed a temporal pattern similar to that of the Ser-9 phosphorylation of GSK-3beta. Treatment with wortmannin or calphostin C or the expression of dominant negative Akt inhibited phosphorylation of GSK-3beta at Ser-9 following the KCl-induced depolarization of SH-SY5Y cells. Moreover, pretreatment with okadaic acid or cyclosporin A blocked the dephosphorylation of GSK-3beta at Ser-9 at 0, 15, and 30 min after KCl-induced depolarization, and the activity of protein phosphatases (PP) 2A and 2B increased at these times. Treatment with nifedipine or calcium-free medium inhibited GSK-3beta dephosphorylation following membrane depolarization, and the amounts of co-immunoprecipitated GSK-3beta and PP2A changed in parallel with GSK-3beta dephosphorylation. Our study demonstrated that KCl-induced depolarization caused undulating GSK-3beta phosphorylation/dephosphorylation, which was regulated for the most part by phosphatidylinositol 3-kinase and Akt (phosphorylation) and PP2A and PP2B (dephosphorylation), respectively.
- ISSN
- 0021-9258 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15799972
https://hdl.handle.net/10371/68487
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