Virdee Kanwar, Yoshida Hirotaka, Peak-Chew Sew, Goedert Michel
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
FEBS Lett. 2007 Jun 12;581(14):2657-62. doi: 10.1016/j.febslet.2007.05.009. Epub 2007 May 11.
Intraneuronal inclusions made of hyperphosphorylated microtubule-associated protein tau are a defining neuropathological characteristic of Alzheimer's disease, and of several other neurodegenerative disorders. Many phosphorylation sites in tau are S/TP sites that flank the microtubule-binding repeats. Others are KXGS motifs in the repeats. One site upstream of the repeats lies in a consensus sequence for AGC kinases. This site (S214) is believed to play an important role in the events leading from normal, soluble to filamentous, insoluble tau. Here, we show that all AGC kinases tested phosphorylated S214. RSK1 and p70 S6 kinase also phosphorylated the neighbouring T212, a TP site that conforms weakly to the AGC kinase consensus sequence. MSK1 phosphorylated S214, as well as S262, a KXGS site in the first repeat, and S305 in the second repeat.
由高度磷酸化的微管相关蛋白tau构成的神经元内包涵体是阿尔茨海默病以及其他几种神经退行性疾病的决定性神经病理学特征。tau蛋白中的许多磷酸化位点是位于微管结合重复序列侧翼的S/TP位点。其他的是重复序列中的KXGS基序。重复序列上游的一个位点位于AGC激酶的共有序列中。这个位点（S214）被认为在从正常的可溶性tau转变为丝状不溶性tau的过程中起重要作用。在这里，我们表明所有测试的AGC激酶都能磷酸化S214。RSK1和p70 S6激酶也能磷酸化相邻的T212，T212是一个TP位点，与AGC激酶共有序列的契合度较弱。MSK1能磷酸化S214，以及第一个重复序列中的KXGS位点S262和第二个重复序列中的S305。
