2004
DOI: 10.1074/jbc.m405131200
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Promotion of Hyperphosphorylation by Frontotemporal Dementia Tau Mutations

Abstract: Mutations in the tau gene are known to cosegregate with the disease in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). However, the molecular mechanism by which these mutations might lead to the disease is not understood. Here, we show that four of the FTDP-17 tau mutations, R406W, V337M, G272V, and P301L, result in tau proteins that are more favorable substrates for phosphorylation by brain protein kinases than the wild-type, largest four-repeat protein 4L and 4L more than 3L. In … Show more

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Cited by 274 publications
(236 citation statements)
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“…The binding between AD P-tau and MAPs seemed to be of hydrophobic nature because it is stimulated at 200 mM NaCl and inhibited at 2 M NaCl; also, it is completely inhibited by Ϸ0.5% Triton X-100 (15,18). AD P-tau can sequester the six isoforms of tau with different affinity; fetal tau binds the least of the six isoforms (19). AD P-tau is able to destroy the microtubules formed with all of the tau isoforms (19).…”
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confidence: 99%
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“…The binding between AD P-tau and MAPs seemed to be of hydrophobic nature because it is stimulated at 200 mM NaCl and inhibited at 2 M NaCl; also, it is completely inhibited by Ϸ0.5% Triton X-100 (15,18). AD P-tau can sequester the six isoforms of tau with different affinity; fetal tau binds the least of the six isoforms (19). AD P-tau is able to destroy the microtubules formed with all of the tau isoforms (19).…”
mentioning
confidence: 99%
“…Recombinant human brain tau on in vitro phosphorylation to a stoichiometry of 4-6 mol sequesters N-tau and disassembles microtubules. On further hyperphosphorylation to Ϸ10 mol of phosphate per 1 mol of protein, tau self-assembles into bundles of PHF͞SF (17,20). Dephosphorylation of AD P-tau as well as PHF converts them into normal-like protein, which promotes assembly and stabilizes microtubules (14,21,22).…”
mentioning
confidence: 99%
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