Data/hora: 10/06/2024 02:37:21

Provedor de dados: | 19
País: | Japan
Título: | Inactivation of integrin-linked kinase induces aberrant tau phosphorylation via sustained activation of glycogen synthase kinase 3 beta in N1E-115 neuroblastoma cells
Autores: | Ishii, Toshiaki; Furuoka, Hidefumi; Muroi, Yoshikage; Nishimura, Masakazu; 石井, 利明; 古岡, 秀文; 室井, 喜景.
Data: | 2003-07-18
Ano: | 2003
Palavras-chave: | ALZHEIMERS-DISEASE NEURITE OUTGROWTH PROTEIN; NEURONS HYPERPHOSPHORYLATION KINASE-3-BETA ACCUMULATION BINDING ROLES.
Resumo: | Integrin-linked kinase (ILK) is a focal adhesion serine/ threonine protein kinase with an important role in integrin and growth factor signaling pathways. Recently, we demonstrated that ILK is expressed in N1E-115 neuroblastoma cells and controls integrin-dependent neurite outgrowth in serum-starved cells grown on laminin (Ishii, T., Satoh, E., and Nishimura, M. ( 2001) J. Biol. Chem. 276, 42994 - 43003). Here we report that ILK controls tau phosphorylation via regulation of glycogen synthase kinase-3beta (GSK-3beta) activity in N1E-115 cells. Stable transfection of a kinase-deficient ILK mutant (DN-ILK) resulted in aberrant tau phosphorylation in N1E-115 cells at sites recognized by the Tau-1 antibody that are identical to some of the phosphorylation sites in paired helical filaments, PHF-tau, in brains of patients with Alzheimer's disease. The tau phosphorylation levels in the DN-ILK-expressing cells are constant under normal and differentiating conditions. On the other hand, aberrant tau phosphorylation was not observed in the parental control cells. ILK inactivation resulted in an increase in the active form but a decrease in the inactive form of GSK-3beta, which is a candidate kinase involved in PHF-tau formation. Moreover, inhibition of GSK-3beta with lithium prevented aberrant tau phosphorylation in the DN-ILK-expressing cells. These results suggest that ILK inactivation results in aberrant tau phosphorylation via sustained activation of GSK-3beta in N1E-115 Cells. ILK directly phosphorylates GSK-3beta and inhibits its activity. Therefore, endogenous ILK protects against GSK-3beta-induced aberrant tau phosphorylation via inhibition of GSK-3beta activity in N1E-115 cells.
Idioma: | Inglês
Identificador: | http://ir.obihiro.ac.jp/dspace/handle/10322/747
Editor: | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Formato: | application/pdf