Characterization of the Phosphoproteome in SLE Patients

• Published in: PloS one Vol. 7; no. 12; p. e53129
• Main Authors: Zhang, Xinzhou, Ma, Hualin, Huang, Jianrong, Dai, Yong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.12.2012; Public Library of Science (PLoS)
• Subjects: Aberration; Actin; Adult; Amino acids; Autoimmune diseases; Autophagy; Bioinformatics; Biology; Biomarkers; Case-Control Studies; Cellular communication; Chromatography; Chronic conditions; Cluster Analysis; Comparative analysis; Cytoskeleton; Disease; Female; Genes; Histone deacetylase; Homology; Hospitals; Humans; Kinases; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - metabolism; Lupus; Lupus Erythematosus, Systemic - metabolism; Male; MAP kinase; Mass spectrometry; Medical research; Medicine; Metabolic Networks and Pathways - physiology; Metabolic pathways; Metabolism; Middle Aged; Models, Biological; Nephrology; Network analysis; Nucleic acids; Pathogenesis; Patients; Peptides; Phosphoproteins - analysis; Phosphoproteins - metabolism; Phosphorylation; Protein kinase C; Protein kinases; Proteins; Proteome - analysis; Proteome - metabolism; Proteomics; Regulators; RelA protein; Rheumatoid arthritis; Rous sarcoma; Sarcoma; Scientific imaging; Signal transduction; Signaling; Systemic lupus erythematosus; Titanium dioxide; Virtual networks; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053129

Protein phosphorylation is a complex regulatory event that is involved in the signaling networks that affect virtually every cellular process. The protein phosphorylation may be a novel source for discovering biomarkers and drug targets. However, a systematic analysis of the phosphoproteome in patients with SLE has not been performed. To clarify the pathogenesis of systemic lupus erythematosus (SLE), we compared phosphoprotein expression in PBMCs from SLE patients and normal subjects using proteomics analyses. Phosphopeptides were enriched using TiO₂ from PBMCs isolated from 15 SLE patients and 15 healthy subjects and then analyzed by automated LC-MS/MS analysis. Phosphorylation sites were identified and quantitated by MASCOT and MaxQuant. A total of 1035 phosphorylation sites corresponding to 618 NCBI-annotated genes were identified in SLE patients compared with normal subjects. Differentially expressed proteins, peptides and phosphorylation sites were then subjected to bioinformatics analyses. Gene ontology(GO) and pathway analyses showed that nucleic acid metabolism, cellular component organization, transport and multicellular organismal development pathways made up the largest proportions of the differentially expressed genes. Pathway analyses showed that the mitogen-activated protein kinase (MAPK) signaling pathway and actin cytoskeleton regulators made up the largest proportions of the metabolic pathways. Network analysis showed that rous sarcoma oncogene (SRC), v-rel reticuloendotheliosis viral oncogene homolog A (RELA), histone deacetylase (HDA1C) and protein kinase C, delta (PRKCD) play important roles in the stability of the network. These data suggest that aberrant protein phosphorylation may contribute to SLE pathogenesis.