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Titolo:
Role of protein phosphatase-2A and-1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain
Autore:
Bennecib, M; Gong, CX; Grundke-Iqbal, I; Iqbal, K;
Indirizzi:
New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA New York State Inst Basic Res Dev Disabil Staten Isl NY USA 10314 314 USA
Titolo Testata:
FEBS LETTERS
fascicolo: 1, volume: 485, anno: 2000,
pagine: 87 - 93
SICI:
0014-5793(20001117)485:1<87:ROPPAI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PAIRED HELICAL FILAMENTS; GLYCOGEN-SYNTHASE KINASE-3; CYCLIN-DEPENDENT KINASE-5; ALZHEIMER-DISEASE BRAIN; RABBIT SKELETAL-MUSCLE; OKADAIC ACID; ABNORMAL PHOSPHORYLATION; XENOPUS OOCYTES; CALYCULIN-A; S6 KINASE;
Keywords:
Alzheimer disease; abnormally hyperphosphorylated tau; protein phosphatase-2A; protein phosphatase-1; glycogen synthase kinase-3; cyclin dependent protein kinase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Iqbal, K New York State Inst Basic Res Dev Disabil, Dept Neurochem, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA New York State Inst Basic Res Dev Disabil 1050 Forest Hill Rd Staten Isl NY USA 10314
Citazione:
M. Bennecib et al., "Role of protein phosphatase-2A and-1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain", FEBS LETTER, 485(1), 2000, pp. 87-93

Abstract

In Alzheimer disease brain the activities of protein phosphatase (PP)-2A and PP-1 are decreased and the microtubule-associated protein tau is abnormally hyperphosphorylated at several sites at serine/threonine, Employing ratforebrain slices kept metabolically active in oxygenated artificial CSF asa model system, we investigated the role of PP-2A/PP-1 in the regulation of some of the major abnormally hyperphosphorylated sites of tau and the protein kinases involved. Treatment of the brain slices with 1.0 muM okadaic acid inhibited similar to 65% of PP-ZA and produced hyperphosphorylation of tau at Ser 198/199/202, Ser 396/404 and Ser 422, No significant changes in the activities of glycogen synthase kinase-3 (GSK-3) and cyclin dependent protein kinases cdk5 and cdc2 were observed. Calyculin A (0.1 muM) inhibitedsimilar to 50% PP-1, similar to 20% PP-2A, 50% GSK-3 and similar to 30% cdk5 but neither inhibited the activity of cyclin AMP dependent protein kinase A (PKA) nor resulted in the hyperphosphorylation of tau at any of the above sites. Treatment of brain slices with 1 muM okadaic acid plus 0.1 muM calyculin A inhibited similar to 100% Of both PP-2A and PP-1, similar to 80% of GSK-3, similar to 50% of cdk5 and similar to 30% of cdc2 but neither inhibited PKA nor resulted in the hyperphosphorylation of tau at any of the above sites. These studies suggest (i) that PP-1 upregulates the phosphorylation of tau at Ser 198/199/202 and Ser 396/404 indirectly by regulating the activities of GSK-3, cdk5 and cdc2 whereas PP-2A regulates the phosphorylation of tau directly by dephosphorylation at the above sites, and (ii) that a decrease in the PP-2A activity leads to abnormal hyperphosphorylation of tau at Ser 198/199/202, Ser 396/404 and Ser 422, (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 09:34:02