title: Protein kinase activity profiling of postmortem human brain tissue.
abstract: BACKGROUND
  Identification of signal transduction pathways that are critically involved in Alzheimer's disease (AD) is essential for the development of disease-specific biomarkers and drug therapy.
  
  
  OBJECTIVE
  This study is aimed at identifying protein kinases and signaling pathways that are activated in AD pathology.
  
  
  METHODS
  Microarray-based kinome profiling was employed for the detection of protein kinase activity in postmortem brain tissue derived from AD and age-matched nondemented control cases. Global serine/threonine kinase activity profiles are identified applying a peptide array system consisting of 140 peptides derived from known kinase substrate sequences covalently attached to porous chips, through which a protein solution is constantly pumped up and down. Peptide phosphorylation is determined by measuring the association of a mixture of fluorescently labeled antibodies, raised against phosphoserine- or phosphothreonine-containing peptides.
  
  
  RESULTS
  Protein lysates from freshly frozen postmortem brain tissue from nondemented controls and pathologically confirmed AD cases show ATP-dependent phosphorylation of peptides. In AD and control cases, peptides that are differentially phosphorylated are identified.
  
  
  CONCLUSIONS
  Protein kinase activity profiling can be used to reveal novel kinases and new signaling pathways involved in AD pathology.
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.forename: Riet
authors.initials: R
authors.lastname: Hilhorst
authors.forename: Rob
authors.initials: R
authors.lastname: Ruijtenbeek
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: Saskia M
authors.initials: SM
authors.lastname: van der Vies
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D011180:Postmortem Changes; D040081:Protein Array Analysis / Q000379:methods; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D011494:Protein Kinases