Protein phosphorylation patterns in serum from schizophrenia patients and healthy controls.
Most proteomic studies to date have attempted to identify changes in protein levels without considering the effects of post-translational modifications (PTM). However, characteristic changes of PTM such as phosphorylation could be biologically informative, as these can give insights into disease and drug mechanisms of action at the functional level. With this in mind, we have conducted a comparative proteomic and phosphoproteomic analysis of blood sera from 20 antipsychotic-naïve schizophrenia patients and 20 matched healthy controls. We used immobilised metal ion affinity chromatography (IMAC) for enrichment of phosphoproteins combined with label-free liquid chromatography-mass spectrometry (LC-MS(E)) for identification and measurement of protein and phosphoprotein levels. The LC-MS(E) analysis of both IMAC-fractions resulted in identification of 35 proteins with altered levels in schizophrenia. Analysis of the enriched fraction resulted in identification of 72 phosphoproteins with altered phosphorylation patterns. Of these, 59 showed changes in phosphorylation only, with no overall change in protein levels. This study provided evidence that schizophrenia patients feature serum abnormalities in phosphorylation of proteins involved in acute phase response and coagulation pathways. Further studies of such phosphorylation-specific changes could lead to a better understanding of the molecular aetiology of schizophrenia, and provide a means of biomarker identification for clinical studies. This article is part of a Special Issue entitled: Integrated omics.
Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT, United Kingdom. jj316@cam.ac.uk
Julian A J
JA
Jaros
Daniel
D
Martins-de-Souza
Hassan
H
Rahmoune
Matthias
M
Rothermundt
F Markus
FM
Leweke
Paul C
PC
Guest
Sabine
S
Bahn
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002846:Chromatography, Affinity / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000097:blood*; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D012559:Schizophrenia / Q000097:blood*
D015415:Biomarkers; D010750:Phosphoproteins