Ser‐262 in human recombinant tau protein is a markedly more favorable site for phosphorylation by CaMKII than PKA or PhK

作者：Juan Sironi, Shu-Hui Yen, Javed A Gondal, Qiongli Wu, Inge Grundke‐Iqbal, Khalid Iqbal · 发表于：FEBS Letters · 年份：1998 · DOI：10.1016/s0014-5793(98)01185-5 · 被引用次数：74 · 研究领域：Microtubule and mitosis dynamics、Alzheimer's disease research and treatments、Cancer-related Molecular Pathways

Several kinases have been shown to phosphorylate tau protein at Ser-262, an important site involved in the regulation of the binding of tau to microtubules. In this study we compared the phosphorylation of tau at Ser-262 by CaMKII, PhK and PKA in vitro as determined by radioimmunoblots developed by the monoclonal antibody 12E8 which recognizes P-Ser-262 and P-Ser-356; and Ab-262, a polyclonal antibody which is specific to unphosphorylated Ser-262 in tau. We found that the phosphorylation at Ser-262 was several times more effective by CaMKII than PKA or PhK. Employing rat brain extract as a source of all brain kinases and KN-62, a specific inhibitor of CaMKII, we found that CaMKII accounts for approximately 45% of phosphorylation at Ser-262. Furthermore, in rat brain slices kept metabolically active in oxygenated artificial CSF, phosphorylation of tau at Ser-262 was (i) increased up to 120% in the presence of bradykinin, a CaMKII activator, and (ii) inhibited by approximately 35% in the presence of KN-62. Thus, CaMKII is a major tau Ser-262 kinase in mammalian brain.