title: Quantitative phosphoproteomic profiling of PINK1-deficient cells identifies phosphorylation changes in nuclear proteins.
abstract: The Parkinson's disease (PD) associated gene PINK1 encodes a protein kinase that mediates the phosphorylation of multiple proteins involved in mitochondrial homeostasis. The broader downstream signaling events mediated by PINK1 kinase activity have not been well documented. We combine quantitative phosphoproteomic strategies with siRNA mediated PINK1 knock down in mammalian cells to identify alterations of phosphorylation events downstream of PINK1. Although down-regulation of PINK1 has no major effect on the proteome expression in these cells, phosphorylation of over one hundred proteins was reduced reflecting basal levels of phosphorylation signaling events downstream of PINK1. Motif analysis of the residues flanking the phosphorylation sites indicates proline-directed kinase specificity. Surprisingly, we found that the downstream signaling nodes included many transcription factors, as well as nuclear proteins involved in DNA and RNA metabolism. Thus, PINK1 dependent phosphorylation signaling may regulate nuclear activities.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China. ljliao@bio.ecnu.edu.cn.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qin
authors.forename: Chaoya
authors.initials: C
authors.lastname: Zheng
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Lujian
authors.initials: L
authors.lastname: Liao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016716:PC12 Cells; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D015398:Signal Transduction; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011392:Proline; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase