Phosphorylation of amyloid-beta at the serine 26 residue by human cdc2 kinase.
The amyloid-beta (Abeta) peptide has been implicated in the pathology of Alzheimer's disease (AD). Using an antisense peptide approach a novel interaction between Abeta and the human cdc2 kinase was identified. The Abeta 1-42, 1-40 and 25-35 peptides were shown to be substrates for the cdc2 kinase and phosphorylated on the Serine 26 residue. Phosphorylated Abeta (pSAbeta) was found in extracts from NT-2 neurons and AD brain. In NT-2 neurons the levels of pSAbeta were increased in the presence of exogenous Abeta and this increase was prevented by a cdc2 protein kinase inhibitor, olomoucine, that also prevented Abeta cytotoxicity. The results from this study suggest that Abeta phosphorylation by cdc2 could play a role in the brain pathology of AD.
Milton
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Department of Molecular Pathology & Clinical Biochemistry, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London.
D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D000595:Amino Acid Sequence / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007701:Kinetin; D051379:Mice; D008970:Molecular Weight; D016571:Neural Networks, Computer; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D010599:Pharmacokinetics; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D012694:Serine / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016375:Antisense Elements (Genetics); D003603:Cytotoxins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011687:Purines; D012694:Serine; C090046:olomoucine; D016203:CDC2 Protein Kinase; D007701:Kinetin