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Tau protein can be transformed into an Alzheimer-like state by phosphorylation with a kinase activity from brain [Biernat et al. (1992) EMBO J. 11, 1593-1597]. Here we show that the phosphorylation at Ser-Pro motifs strongly decreases tau's affinity for Microtubules. The major reduction occurs during the first of the three main stages of phosphorylation. The data explain the lower Stability of microtubules...
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