title: Quantitative phosphoproteomics-based molecular network description for high-resolution kinase-substrate interactome analysis.
abstract: Phosphorylation-dependent cellular signaling is known to play a diverse role in regulating multiple cellular processes such as proliferation, differentiation and apoptosis. Recent technological advances in mass spectrometry-based phosphoproteomics have enabled us to measure network-wide signaling dynamics in a comprehensive and quantitative manner. As conventional protein-protein interaction (PPI) information-based network analysis is insufficient to systematically analyze phosphorylation site-dependent complex interaction dynamics, here we develop and evaluate a platform to provide a high-resolution molecular network description for kinase-substrate interactome analysis.
  
  
  
  In this study, we developed a Cytoscape-based bioinformatical platform named 'Post Translational Modification mapper (PTMapper)' to integrate PPI data with publicly available kinase-substrate relations at the resolution of phosphorylated amino acid residues. The previous phosphoproteome data on EGF-induced cellular signaling in glioblastoma stem cells was applied to evaluate our platform, leading to discovery of phosphorylation-dependent crucial signaling modulation in the p70S6K1-related pathway. Our study revealed that high-resolution cellular network description of phosphorylation-site dependent kinase-substrate signaling regulation should accelerate phosphoproteomics-based exploration of novel drug targets in the context of each disease-related signaling.
  
  
  
  PTMapper and the example data for construction of phosphorylation site-oriented networks are available at https://github.com/y-narushima/PTMapper
  
  
  
  moyama@ims.u-tokyo.ac.jp
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Narushima
authors.affiliation: Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kozuka-Hata
authors.affiliation: Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.affiliation: Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Inoue
authors.affiliation: Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oyama
mesh_terms: D019295:Computational Biology / Q000379:methods; D005909:Glioblastoma / Q000737:chemistry; D006801:Humans; D014411:Neoplastic Stem Cells / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry*; D025941:Protein Interaction Mapping / Q000379:methods; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction
chemical_list: D010750:Phosphoproteins; D010770:Phosphotransferases