Muñoz-Montaño J R, Moreno F J, Avila J, Díaz-Nido J
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
J Neurosci Res. 1999 Feb 1;55(3):278-85. doi: 10.1002/(SICI)1097-4547(19990201)55:3<278::AID-JNR2>3.0.CO;2-2.
Glycogen synthase kinase-3gamma (GSK-3beta) is a multifunctional protein kinase that phosphorylates a variety of substrates including the neuronal-specific microtubule-associated protein tau. Here we report that the down-regulation of the GSK-3beta protein is an early event in the course of the differentiation of human neuroblastoma IMR-32 cells. This decline in GSK-3beta is accompanied by a significant decrease in the phosphorylation state of tau protein. A noteworthy increase in tau protein expression also takes place later during the differentiation of IMR-32 cells. The augmented expression and diminished phosphorylation of tau protein in differentiated IMR-32 cells can be correlated with increments in the assembly of microtubules and in the association of tau with microtubules. These results suggest a contribution of a decrease in GSK-3beta to molecular events leading to neuroblastoma cell differentiation. Among these, tau protein dephosphorylation might favor microtubule stabilization within neurites.
糖原合酶激酶-3γ（GSK-3β）是一种多功能蛋白激酶，可磷酸化多种底物，包括神经元特异性微管相关蛋白tau。在此我们报告，GSK-3β蛋白的下调是人类神经母细胞瘤IMR-32细胞分化过程中的早期事件。GSK-3β的这种下降伴随着tau蛋白磷酸化状态的显著降低。在IMR-32细胞分化后期，tau蛋白表达也有显著增加。分化的IMR-32细胞中tau蛋白表达增加和磷酸化减少与微管组装增加以及tau与微管的结合增加相关。这些结果表明，GSK-3β的减少对导致神经母细胞瘤细胞分化的分子事件有作用。其中，tau蛋白去磷酸化可能有利于神经突内微管的稳定。
