An atlas of human kinase regulation. Issue 12 (1st December 2016)

• Record Type: Journal Article
• Authors: Ochoa, David; Jonikas, Mindaugas; Lawrence, Robert T; El Debs, Bachir; Selkrig, Joel; Typas, Athanasios; Villén, Judit; Santos, Silvia DM; Beltrao, Pedro
• Is Part Of: Molecular systems biology. Volume 12:Issue 12(2016:Dec.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-12-01
• Subjects: cell fate -- human -- kinase activity -- phosphoproteomics -- signaling; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.20167295
• Languages: English
• ISSNs: 1744-4292

Abstract

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. Synopsis: Analysis of human phosphoproteomic data from 399 perturbations shows that substrate‐based kinase activity inference can inform on the global cellular signaling state and the properties of the decision‐making process. Activities for 215 human kinases in 399 perturbations are inferred based on the phosphoproteomic changes reported in 41 different studies. The kinase regulation profile can serve as a molecular fingerprint that reveals similarities and differences between signaling states. Human kinases that are often regulated (i.e. generalist kinases) are found to occupy central positions in the signaling network. Co‐regulation between kinases and phosphosites or complexes identifies novel kinase target effectors. Abstract : Analysis of human phosphoproteomic data from 399 perturbations shows that substrate‐based kinase activity inference can inform on the global cellular signaling state and the properties of the decision‐making process.