Sites of phosphorylation in tau and factors affecting their regulation.
Sites of phosphorylation in tau and factors affecting their regulation.
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DOI：
10.1042/bss0670073
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发表时间：
2000-02
期刊：
影响因子：
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通讯作者：
B. Anderton;J. Betts;W. Blackstock;J. Brion;S. Chapman;J. Connell;R. Dayanandan;J. Gallo;G. Gibb;D. Hanger;M. Hutton;E. Kardalinou;K. Leroy;S. Lovestone;T. Mack;C. Reynolds;M. V. van Slegtenhorst
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文献类型：
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作者：
B. Anderton;J. Betts;W. Blackstock;J. Brion;S. Chapman;J. Connell;R. Dayanandan;J. Gallo;G. Gibb;D. Hanger;M. Hutton;E. Kardalinou;K. Leroy;S. Lovestone;T. Mack;C. Reynolds;M. V. van Slegtenhorst
微管相关蛋白tau是阿尔茨海默病中成对螺旋丝（phf）的主要成分。PHF-tau是高度磷酸化的，到目前为止已经确定了25个磷酸化位点。许多这些位点是丝氨酸或苏氨酸残基，在序列中紧随脯氨酸残基，因此是脯氨酸定向激酶的候选磷酸化位点。在体外，糖原合成酶激酶-3 （GSK-3）、细胞外信号相关激酶-1和-2，以及丝裂原活化蛋白激酶，p38激酶和c-jun n-末端激酶，都能磷酸化这些位点中的许多位点，尽管对特定位点的效率不同。转染细胞和神经元的磷酸化研究表明，GSK-3比其他脯氨酸定向激酶更广泛地磷酸化tau蛋白。tau突变已被证明影响GSK-3对tau的体外磷酸化。Arg406- >Trp (R406W) tau突变也影响细胞中的tau磷酸化。
The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp (R406W) tau mutation also affects tau phosphorylation in cells.