TY - JOUR AU - Juhnn, Yong-Sung AB -

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 3β (GSK-3β) in this process has not been elucidated. Thus, this study was performed to examine whether membrane depolarization can regulate the phosphorylation of GSK-3β 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-3β 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 β-catenin contents showed a temporal pattern similar to that of the Ser-9 phosphorylation of GSK-3β. Treatment with wortmannin or calphostin C or the expression of dominant negative Akt inhibited phosphorylation of GSK-3β 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-3β 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-3β dephosphorylation following membrane depolarization, and the amounts of co-immunoprecipitated GSK-3β and PP2A changed in parallel with GSK-3β dephosphorylation. Our study demonstrated that KCl-induced depolarization caused undulating GSK-3β phosphorylation/dephosphorylation, which was regulated for the most part by phosphatidylinositol 3-kinase and Akt (phosphorylation) and PP2A and PP2B (dephosphorylation), respectively.

TI - Membrane Depolarization Induces the Undulating Phosphorylation/Dephosphorylation of Glycogen Synthase Kinase 3β, and This Dephosphorylation Involves Protein Phosphatases 2A and 2B in SH-SY5Y Human Neuroblastoma Cells * JF - Journal of Biological Chemistry DO - 10.1074/jbc.m413987200 DA - 2005-06-10 UR - https://www.deepdyve.com/lp/american-society-for-biochemistry-and-molecular-biology/membrane-depolarization-induces-the-undulating-phosphorylation-yO00DjOTRY SP - 22044 EP - 22052 VL - 280 IS - 23 DP - DeepDyve ER -