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 condi-
tions from a compilation of nearly 3 million 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 essen-
tial 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.