Lesort M, Jope R S, Johnson G V
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 35294-0017, USA.
J Neurochem. 1999 Feb;72(2):576-84. doi: 10.1046/j.1471-4159.1999.0720576.x.
The modulation of tau phosphorylation in response to insulin was examined in human neuroblastoma SH-SY5Y cells. Insulin treatment resulted in a transient increase in tau phosphorylation followed by a decrease in tau phosphorylation that correlated directly with a sequential activation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). The insulin-induced increase in tau phosphorylation and concurrent activation of GSK-3beta was rapid (<2 min) and transient, and was associated with increased tyrosine phosphorylation of GSK-3beta. The increase in GSK-3beta tyrosine phosphorylation corresponded directly to an increase in the association of Fyn tyrosine kinase with GSK-3beta, and Fyn immunoprecipitated from cells treated with insulin for 1 min phosphorylated GSK-3beta to a significantly greater extent than Fyn immunoprecipitated from control cells. Subsequent to the increase in GSK-3beta activation and tau phosphorylation, treatment of cells with insulin for 60 min resulted in a dephosphorylation of tau and a decrease in GSK-3beta activity. Thus, insulin rapidly and transiently activated GSK-3beta and modulated tau phosphorylation, alterations that may contribute to neuronal plasticity.
在人神经母细胞瘤SH-SY5Y细胞中检测了tau蛋白磷酸化对胰岛素的反应调节。胰岛素处理导致tau蛋白磷酸化短暂增加，随后tau蛋白磷酸化减少，这与糖原合酶激酶-3β（GSK-3β）的顺序激活和失活直接相关。胰岛素诱导的tau蛋白磷酸化增加和GSK-3β的同时激活迅速（<2分钟）且短暂，并且与GSK-3β酪氨酸磷酸化增加有关。GSK-3β酪氨酸磷酸化的增加直接对应于Fyn酪氨酸激酶与GSK-3β结合的增加，并且从用胰岛素处理1分钟的细胞中免疫沉淀的Fyn比从对照细胞中免疫沉淀的Fyn磷酸化GSK-3β的程度明显更大。在GSK-3β激活和tau蛋白磷酸化增加之后，用胰岛素处理细胞60分钟导致tau蛋白去磷酸化和GSK-3β活性降低。因此，胰岛素迅速且短暂地激活GSK-3β并调节tau蛋白磷酸化，这些改变可能有助于神经元可塑性。
