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• W2014190915 endingPage "17" @default.
• W2014190915 startingPage "1" @default.
• W2014190915 abstract "Pyramidal neurons in affected regions of Alzheimer's disease (AD) brain contain neurofibrillary tangles (NFT), aggregates of paired helical filaments (PHF) composed mainly of phosphorylated microtubule-associated protein tau. To explore the role of tau phosphorylation in the aggregation of tau into PHF, we constructed mammalian cell culture systems producing high levels of intracellular phosphorylated tau. COS-1 fibroblast-like cells were transiently transfected to simultaneously express tau, MAP kinase (MAPK), and MAP kinase kinase (MAPKK), or alternatively to express tau and glycogen synthase kinase 3 (GSK3). B103 neuron-like cells (which contain MAPK but little tau or GSK3) were stably transfected to express tau or tau and GSK3. In both systems, GSK3-transfected cells contained tauAT8/M (defined by AT8 staining and tauPHF-like mobility), but MAPK-transfected cells required phosphatase inhibitors, such as okadaic acid (OKA) or calyculin (CAL), to produce tauAT8/M. In vitro, the same concentrations of CAL and OKA inhibit phosphatases 1 and 2A (PP1 and PP2A), except that 100–1000 times as much OKA is needed to inhibit PP1. Inducing tau phosphorylation at the AT8 site in MAPK-transfected cells required 2–10 times more OKA than CAL, suggesting both PP1 and PP2A helped block the phosphorylation. Though levels of tauAT8/M reached 2–8% of total cellular proteins in COS-1 cells, the ratio of particulate to supernatant tau levels did not increase, and no tangles were observed; perhaps post-translational modifications or co-aggregating proteins are needed to induce PHF." @default.
• W2014190915 created "2016-06-24" @default.
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• W2014190915 date "1995-12-01" @default.
• W2014190915 modified "2023-09-23" @default.
• W2014190915 title "Overexpressed tau protein in cultured cells is phosphorylated without formation of PHF: implication of phosphoprotein phosphatase involvement" @default.
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• W2014190915 doi "https://doi.org/10.1016/0169-328x(95)00111-5" @default.
• W2014190915 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8750856" @default.
• W2014190915 hasPublicationYear "1995" @default.
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