In vitro analysis of tau phosphorylation sites and its biological activity / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
;
(4): 13-16, 2002.
Artigo
em Inglês
| WPRIM
| ID: wpr-252443
ABSTRACT
<p><b>OBJECTIVE</b>To explore the association between the abnormal phosphorylation sites found in Alzheimer disease (AD) tau and the inhibition of its biological activity.</p><p><b>METHODS</b>Ultracentrifugation, chromatography, manual Edman degradation and autosequence techniques were used to prepare and phosphorylate human recombinant tau, isolate and purify 32P tau peptides and determine phosphorylation sites.</p><p><b>RESULTS</b>Phosphorylation of tau by casein kinase 1 (CK-1), cyclic AMP-dependent protein kinase (PKA) and glycogen synthetase kinase 3 (GSK-3) separately inhibited its biological activity and the inhibition of this activity by (CSK-3 was significantly increased if tau was prephosphorylated by CK-1 or PKA. The most potent inhibition was seen by a combined phosphorylation of tau with PKA and GSK-3. The treatment of tau by PKA and GSK-3 combination induced phosphorylation of tau at Ser-195, Ser-198, Ser-199, Ser-202, Thr-205, Thr-231, Ser-235, Ser-262, Ser-356, Ser-404, whereas Thr-181, Ser-184, Ser-262, Ser-356 and Ser-400 were phosphorylated by GSK-3 alone under the same condition.</p><p><b>CONCLUSION</b>Phosphorylation of tau by PKA plus GSK-3 at Thr-205 might play a key role in tau pathology in AD.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Proteínas Quinases
/
Sítios de Ligação
/
Técnicas In Vitro
/
Proteínas tau
/
Proteínas Quinases Dependentes de AMP Cíclico
/
Quinase 3 da Glicogênio Sintase
/
Caseína Quinases
/
Doença de Alzheimer
/
Metabolismo
Tipo de estudo:
Guia de Prática Clínica
Limite:
Humanos
Idioma:
Inglês
Revista:
Chinese Medical Sciences Journal
Ano de publicação:
2002
Tipo de documento:
Artigo
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