Differential expression of brain proteins in glycogen synthase kinase‐3 transgenic mice: A proteomics point of view
Differential expression of brain proteins in glycogen synthase kinase‐3 transgenic mice: A proteomics point of view
复制标题
糖原合酶激酶-3转基因小鼠脑蛋白的差异表达：蛋白质组学的观点
作者：
K. Tilleman;I. Stevens;K. Spittaels;C. V. Haute;S. Clerens;G. van den Bergh;H. Geerts;F. van Leuven;F. Vandesande;L. Moens
阿尔茨海默病的标志之一是大脑中的神经原纤维缠结（NFT）。NFT主要由过度磷酸化形式的tau蛋白组成，该蛋白通过微管结合负责神经元细胞骨架的稳定，并且在过度磷酸化形式下无法正常发挥作用。糖原合成酶激酶- 3β (GSK3β)能够在细胞环境中磷酸化tau蛋白，这可能在这些NFT的形成中发挥作用。为了进一步了解GSK‐3β在大脑中的作用，我们定量比较了GSK3β[S9A]转基因小鼠和野生型小鼠大脑提取物的二维电泳图谱。51个点的综合强度差异至少为1.5倍。这些斑点随后被质谱鉴定出来。鉴定了几个与GSK3β发挥作用的信号转导途径相关的蛋白质，表明我们鉴定的蛋白质群体包括一些GSK3β的下游蛋白质。该研究可能有助于填补GSK3β与其底物之间的空白，并最终磷酸化tau。
One of the landmarks of Alzheimer’s disease are neurofibrillary tangles (NFT) in the brain. NFT mainly consist of a hyperphosphorylated form of the protein tau, which is responsible for stabilisation of the neuronal cytoskeleton by microtubule binding and is unable to function properly in its hyperphosphorylated form. Glycogen synthase kinase‐3β (GSK3β) is able to phosphorylate tau in a cellular context which could play a role in the formation of these NFT. In order to learn more about the effect of GSK‐3β in the brain, two‐dimensional electrophoresis patterns of cerebrum extracts of GSK3β[S9A] transgenic mice and wild type mice were compared quantitatively. Fifty‐one spots were identified as being different in integrated intensity by at least a factor 1.5. The spots were subsequently identified by mass spectrometry. Identification of several proteins linked to signal transduction pathways in which GSK3β plays a role, indicates that our population of identified proteins includes some down stream proteins of GSK3β. This study may contribute to filling the gaps between GSK3β, its substrates and finally the phosphorylation of tau.
DOI：
10.1073/pnas.83.11.4040
发表时间：
1986-06-01
影响因子：
11.1
作者：
WOOD, JG;MIRRA, SS;BINDER, LI
通讯作者：
BINDER, LI