An atlas of human kinase regulation

作者：Ochoa David; Jonikas Mindaugas; Lawrence Robert T; El Debs Bachir; Selkrig Joel; Typas Athanasios; Villen Judit; Santos Silvia D M; Beltrao Pedro^*

来源：Molecular Systems Biology, 2016, 12(12): 888.

DOI：10.15252/msb.20167295

• cell fate
• human
• kinase activity
• phosphoproteomics
• signaling

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.

• 出版日期2016-12