Inferring the sign of kinase-substrate interactions by combining quantitative phosphoproteomics with a literature-based mammalian kinome network


Journal Article

Protein phosphorylation is a reversible post-translational modification commonly used by cell signaling networks to transmit information about the extracellular environment into intracellular organelles for the regulation of the activity and sorting of proteins within the cell. For this study we reconstructed a literature-based mammalian kinase-substrate network from several online resources. The interactions within this directed graph network connect kinases to their substrates, through specific phosphosites including kinase-kinase regulatory interactions. However, the "signs" of links, activation or inhibition of the substrate upon phosphorylation, within this network are mostly unknown. Here we show how we can infer the "signs" indirectly using data from quantitative phosphoproteomics experiments applied to mammalian cells combined with the literature-based kinase-substrate network. Our inference method was able to predict the sign for 321 links and 153 phosphosites on 120 kinases, resulting in signed and directed subnetwork of mammalian kinase-kinase interactions. Such an approach can rapidly advance the reconstruction of cell signaling pathways and networks regulating mammalian cells. © 2010 IEEE.

Full Text

Duke Authors

Cited Authors

  • Hernandez, M; Lachmann, A; Zhao, S; Xiao, K; Ma'ayan, A

Published Date

  • September 6, 2010

Published In

  • 10th Ieee International Conference on Bioinformatics and Bioengineering 2010, Bibe 2010

Start / End Page

  • 180 - 184

Digital Object Identifier (DOI)

  • 10.1109/BIBE.2010.75

Citation Source

  • Scopus