Document Detail


Quantitative analysis of brain nuclear phosphoproteins identifies developmentally regulated phosphorylation events.
MedLine Citation:
PMID:  18823140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protein phosphorylation is a globally adopted and tightly controlled post-translational modification, and represents one of the most important molecular switching mechanisms that govern the entire spectrum of biological processes. In the central nervous system, it has been demonstrated that phosphorylation of key proteins mediating chromatin remodeling and gene transcription plays an important role controlling brain development, synaptogenesis, learning and memory. Many studies have focused on large scale identification of phosphopeptides in brain tissue. These studies have identified phosphorylation site specific motifs useful for predicting protein kinase substrates. In this study, we applied a previously developed quantitative approach, stable isotope labeling of amino acids in mammals (SILAM), to quantify changes in the phosphorylation of nuclear proteins between a postnatal day one (p1) and a p45 rat brain cortex. Using a 15N labeled rat brain as an internal standard, we quantified 705 phosphopeptides in the p1 cortex and 1477 phosphopeptides in the p45 cortex, which translates to 380 and 585 phosphoproteins in p1 and p45 cortex, respectively. Bioinformatic analysis of the differentially modified phosphoproteins revealed that phosphorylation is upregulated on multiple components of chromatin remodeling complexes in the p1 cortex. Taken together, we demonstrated for the first time the usefulness of employing stable isotope labeled rat tissue for global quantitative phosphorylation analysis.
Authors:
Lujian Liao; Daniel B McClatchy; Sung Kyu Park; Tao Xu; Bingwen Lu; John R Yates
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-30
Journal Detail:
Title:  Journal of proteome research     Volume:  7     ISSN:  1535-3893     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-07     Completed Date:  2009-01-07     Revised Date:  2010-12-03    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4743-55     Citation Subset:  IM    
Affiliation:
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Brain / growth & development*,  metabolism*
Brain Chemistry*
Cerebellar Cortex / chemistry
Computational Biology / methods
Isotope Labeling
Nuclear Proteins / analysis*
Phosphopeptides / analysis
Phosphoproteins / analysis*,  metabolism
Phosphorylation
Rats
Rats, Sprague-Dawley
Reference Standards
Reproducibility of Results
Grant Support
ID/Acronym/Agency:
5R01 MH067880-02/MH/NIMH NIH HHS; P30 NS057096/NS/NINDS NIH HHS; P30 NS057096-03/NS/NINDS NIH HHS; P41 RR011823-13/RR/NCRR NIH HHS; R01 MH067880-06/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Phosphopeptides; 0/Phosphoproteins
Comments/Corrections

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