PP2B isolated from human brain preferentially dephosphorylates Ser-262 and Ser-396 of the Alzheimer disease abnormally hyperphosphorylated tau.
PP2B is one of the major serine/threonine phosphatases in the brain. We quantitated the dephosphorylation of various sites of Alzheimer disease abnormally hyperphosphorylated tau by PP2B purified from six (three Alzheimer and three control) autopsied human brains. The purified PP2B was essentially homogenous holoenzyme as determined by SDS-PAGE, Western blot analyses and biochemical characterization. Purified PP2B from all six brains efficiently dephosphorylated (32)P-tau with specific activities ranging from 684-1286 pmol (32)Pi/mg/min. Estimated by dot-blot analyses, the purified PP2B (on average from six brains) dephosphorylated Alzheimer tau at pS199, pT217, pS262, pS396 and pS422 by 38%, 32%, 63%, 78%, and 32%, respectively. Dephosphorylation of tau at pT181, pS202, pT205, pT212, pS214, and pS404 by PP2B was undetectable. The preferential dephosphorylation of Ser262 and Ser396 by PP2B suggests a possible involvement of this phosphatase in Alzheimer neurofibrillary degeneration.
Rahman
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Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Grundke-Iqbal
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Iqbal
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D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D001921:Brain / Q000201:enzymology*; D019703:Calcineurin / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D016874:Neurofibrillary Tangles / Q000201:enzymology; D010766:Phosphorylation; D011817:Rabbits; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D016875:tau Proteins / Q000378:metabolism*
D000906:Antibodies; D016875:tau Proteins; D012694:Serine; D019703:Calcineurin