FRAT1 peptide decreases Aβ production in swAPP751 cells

FEBS Letters

Zhou, Yan¹  Ryder, John¹  Su, Yuan¹  Li, Baolin¹  Liu, Feng¹  Ni, Binhui¹ 

[1] Lilly Research Laboratories, Eli Lilly and company, Lilly Corporate Center, Drop code 0510, Indianapolis, IN 46285, USA

关键词: FRAT;    Glycogen synthase kinase;    Amyloid;    Amyloid precursor protein;    Alzheimer's disease;    Kinase activity;   

DOI  :  10.1016/S0014-5793(03)01042-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently, LiCl has been shown to inhibit amyloid β peptide secretion in association with diminished glycogen synthase kinase β (GSK3β) activity. However, it remains unclear if direct inhibition of GSK3β activity will result in decreased Aβ production. requently earranged in dvanced -cell lymphomas (FRAT1) protein is a negative regulator of GSK3α/β kinase activity. To examine whether direct inhibition of GSK3α/β kinase activity can lower Aβ production, a FRAT1 peptide was expressed in swAPP₇₅₁ cells that produce high levels of Aβ. Our data demonstrate that cellular expression of FRAT1 peptide in swAPP₇₅₁ cells increases both GSK3α and β phosphorylation on Ser21 and Ser9, respectively, while inhibiting kinase activity of both isoforms. Moreover, as a result of FRAT1 expression, the production of both total Aβ and Aβ_1-42 was significantly decreased. Thus, we provide evidence that direct regulation of GSK3α/β by FRAT1 peptide significantly decreases Aβ production in swAPP₇₅₁ cells.

【 授权许可】

Unknown