14-3-3Zeta does not increase GSK3beta-mediated tau phosphorylation in cell culture models.
14-3-3Zeta does not increase GSK3beta-mediated tau phosphorylation in cell culture models.
复制标题
14-3-3Zeta 不会增加细胞培养模型中 GSK3beta 介导的 tau 磷酸化。
DOI：
10.1016/j.neulet.2005.04.101
复制
发表时间：
2005
影响因子：
2.5
通讯作者：
Johnson,GailVW
中科院分区：
文献类型：
--
作者：
Matthews,ToriA;Johnson,GailVW
Tau是一种神经元微管相关蛋白，其功能受位点特异性磷酸化调节。一种可能在体内调节tau磷酸化状态中起重要作用的蛋白激酶是糖原合成酶激酶（GSK）3β。GSK 3 β的活性受特异性蛋白质-蛋白质相互作用的调节，并且最近报道了14-3-3 β（可以充当支架的蛋白质家族的成员）与从牛脑中分离的大蛋白复合物中的GSK 3 β共纯化[A. Agarwal-Mawal，H.Y. Qureshi，P.W.卡费什岛Yuan，云南杜父花D.汉河，巴西-地Lin，H.K. Paudel，14-3-3将糖原合成酶激酶-3 β连接到脑微管相关的tau磷酸化复合物内的tau，J.Biol.Chem.278（2003）12722-12728]。本研究的目的是确定14-3-3 β是否可以作为支架蛋白促进GSK 3 β与tau的相互作用，并随后增强GSK 3 β介导的tau过度磷酸化。我们使用细胞培养模型、免疫沉淀和蛋白质印迹来检测GSK 3 β和14-3-3 β与外源和内源表达蛋白的相互作用。我们发现，在我们的实验条件下，GSK 3 β、14-3-3 β和tau在这些细胞模型中不相互作用，并且GSK 3 β介导的tau磷酸化不受14-3-3 β存在的影响。这些数据表明，14-3-3 β可能不直接与脑中的GSK 3 β和tau相互作用，但可能通过与其他蛋白质结合间接促进相互作用。
Tau is a neuronal microtubule-associated protein whose function is regulated by site-specific phosphorylation. One protein kinase that is likely to play an important role in regulating the phosphorylation state of tau in vivo is glycogen synthase kinase (GSK) 3β. The activity of GSK3β is regulated by specific protein–protein interactions and 14-3-3ζ, a member of a protein family that can act as scaffolds, was recently reported to co-purify with GSK3β in a large protein complex that was isolated from bovine brain [A. Agarwal-Mawal, H.Y. Qureshi, P.W. Cafferty, Z. Yuan, D. Han, R. Lin, H.K. Paudel, 14-3-3 connects glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau phosphorylation complex, J. Biol. Chem. 278 (2003) 12722–12728]. The purpose of this study was to determine if 14-3-3ζ could act as a scaffolding protein to promote the interaction of GSK3β with tau and subsequently, enhance GSK3β-mediated tau hyperphosphorylation. We used cell culture models, immunoprecipitation, and Western blotting to examine the interaction of GSK3β and 14-3-3ζ with both exogenously and endogenously expressed proteins. We found that GSK3β, 14-3-3ζ and tau do not interact in these cellular models under our experimental conditions and that GSK3β-mediated tau phosphorylation is not effected by the presence of 14-3-3ζ. These data indicate that 14-3-3ζ may not be directly interacting with GSK3β and tau in the brain, but may indirectly facilitate the interactions by binding to other proteins.