An atlas of human kinase regulation |
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| Authors: | David Ochoa Mindaugas Jonikas Robert T Lawrence Bachir El Debs Joel Selkrig Athanasios Typas Judit Villén Silvia DM Santos Pedro Beltrao |
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| Affiliation: | 1. European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL‐EBI), Hinxton, UK;2. Quantitative Cell Biology Group, MRC Clinical Sciences Centre, Imperial College, London, UK;3. Department of Genome Sciences, University of Washington, Seattle, WA, USA;4. Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany |
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| 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. |
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| Keywords: | cell fate human kinase activity phosphoproteomics signaling |
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