title: An atlas of human kinase regulation.
abstract: The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision-making has been limited by the small number of simultaneously monitored phospho-regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs. Co-regulation along the conditions predicts kinase-complex and kinase-substrate associations. Additionally, the kinase regulation profile acts as a molecular fingerprint to identify related and opposing signaling states. Using this atlas, we identified essential mediators of stem cell differentiation, modulators of Salmonella infection, and new targets of AKT1. This provides a global view of human phosphorylation-based signaling and the necessary context to better understand kinase-driven decision-making.
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Ochoa
authors.affiliation: Quantitative Cell Biology Group, MRC Clinical Sciences Centre, Imperial College, London, UK.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Jonikas
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Lawrence
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Bachir
authors.initials: B
authors.lastname: El Debs
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Joel
authors.initials: J
authors.lastname: Selkrig
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Typas
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Judit
authors.initials: J
authors.lastname: Villén
authors.affiliation: Quantitative Cell Biology Group, MRC Clinical Sciences Centre, Imperial College, London, UK.
authors.forename: Silvia Dm
authors.initials: SD
authors.lastname: Santos
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK pbeltrao@ebi.ac.uk.
authors.forename: Pedro
authors.identifier: http://orcid.org/0000-0002-2724-7703
authors.initials: P
authors.lastname: Beltrao
mesh_terms: D002454:Cell Differentiation; D030562:Databases, Protein; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods*
chemical_list: D011494:Protein Kinases
keywords: cell fate; human; kinase activity; phosphoproteomics; signaling