Protein kinase activity profiling of postmortem human brain tissue

Neuro-degenerative Diseases
Jeroen J M HoozemansSaskia M van der Vies

Abstract

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. This study is aimed at identifying protein kinases and signaling pathways that are activated in AD pathology. 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. 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. Protein kinase activity profiling can be used to re...Continue Reading

References

Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
Jul 2, 2009·Cancer Research·Arend H SikkemaEveline S J M de Bont
Dec 3, 2009·Neuropharmacology·Lenka Munoz, Alaina J Ammit
Aug 12, 2010·Current Pharmaceutical Design·Miguel Medina, Jesús Avila

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Citations

Jan 1, 2012·Scientifica·Maikel P Peppelenbosch
Nov 1, 2015·Journal of Alzheimer's Disease : JAD·Andrea F N RosenbergerSaskia M van der Vies
Oct 28, 2016·Journal of Neurogenetics·Li-Lian YuanVanja Duric
Feb 17, 2017·Biochemical Society Transactions·Akanksha BaharaniScott Napper

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