title: A pool of beta-tubulin is hyperphosphorylated at serine residues in Alzheimer disease brain.
abstract: 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 approximately 11 pmol phosphate/microg protein in 100,000 x g pellet from AD compared with age-matched control brains was found. Tau protein, which is hyperphosphorylated in AD can only account for approximately 4 pmol phosphate/microg protein, suggesting the presence of non-tau hyperphosphorylated proteins in the diseased brain. Western blot analysis with phosphoserine antibodies revealed a approximately 54 kDa non-tau protein to be significantly hyperphosphorylated in AD compared with age-matched control cases in the particulate fraction. The approximately 54 kDa protein was purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified as beta-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.
authors.affiliation: Center for Developmental Neuroscience, The Graduate School and University Center of the City University of New York, NY 10016-4309, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vijayan
authors.forename: E
authors.initials: E
authors.lastname: El-Akkad
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010710:Phosphates / Q000032:analysis; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D012995:Solubility; D014404:Tubulin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D010710:Phosphates; D014404:Tubulin; D010768:Phosphoserine