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A pool of β‐tubulin is hyperphosphorylated at serine residues in Alzheimer disease brain
Author(s) -
Vijayan Shrijay,
El-Akkad Ezzat,
Grundke-Iqbal Inge,
Iqbal Khalid
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03201-x
Subject(s) - biochemistry , serine , western blot , hyperphosphorylation , alzheimer's disease , phosphatase , gel electrophoresis , tau protein , polyacrylamide gel electrophoresis , tubulin , chemistry , microbiology and biotechnology , protein phosphatase 2 , biology , phosphoserine , phosphorylation , microtubule , enzyme , medicine , disease , gene
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.