A pool of β‐tubulin is hyperphosphorylated at serine residues in Alzheimer disease brain

FEBS Letters

El-Akkad, Ezzat¹  Vijayan, Shrijay²  Grundke-Iqbal, Inge¹  Iqbal, Khalid² 

[1] Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA;Center for Developmental Neuroscience, The Graduate School and University Center of the City University of New York, 365 Fifth Avenue, New York, NY 10016-4309, USA

关键词: Alzheimer disease;    Hyperphosphorylation;    β-Tubulin;    Phosphoserine;    AD;    Alzheimer disease;    PP;    protein phosphatase;    SDS–PAGE;    sodium dodecyl sulfate–polyacrylamide gel electrophoresis;    PHF;    paired helical filament;    MES;    2-[N-morpholino]ethanesulfonic acid;    IMAC;    iron metal affinity chromatography;    TBST;    Tris-buffered saline with Tween 20;    MS-MALDI;    mass spectrometry-matrix assisted laser desorption/ionization;   

DOI  :  10.1016/S0014-5793(01)03201-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In Alzheimer disease (AD) brain, activities of protein phosphatase (PP)-2A/PP-1 which are known to be associated with microtubules are compromised and are probably a cause of neurofibrillary degeneration through hyperphosphorylation of microtubule proteins. In the present study, an increase of ∼11 pmol phosphate/μg protein in 100 000×g pellet from AD compared with age-matched control brains was found. Tau protein, which is hyperphosphorylated in AD can only account for ∼4 pmol phosphate/μg protein, suggesting the presence of non-tau hyperphosphorylated proteins in the diseased brain. Western blot analysis with phosphoserine antibodies revealed a ∼54 kDa non-tau protein to be significantly hyperphosphorylated in AD compared with age-matched control cases in the particulate fraction. The ∼54 kDa protein was purified by preparative sodium dodecyl sulfate–polyacrylamide gel electrophoresis and identified as β-tubulin by immunolabeling with specific antibodies, mass spectrometry analysis and by N-terminal amino acid sequencing. The purified protein was hyperphosphorylated at serine residues in AD.

【 授权许可】

Unknown