Kinases and Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit"

Temporal control over protein phosphorylation and dephosphorylation is crucial for accurate chromosome segregation and for
completion of the cell division cycle during exit from mitosis.
Degradation of mitotic cyclins and activation of Cdk‐counteracting phosphatases lead to protein dephosphorylation. In budding yeast, the
Cdc14 phosphatase is thought to be a major regulator at this time, while in higher eukaryotes PP2A phosphatases take a dominant role. We use
time-resolved phosphoproteome analysis in budding yeast to evaluate the respective contributions of the kinases and phosphatase input. This
reveals that successive inactivation of Cdks and of the mitotic kinase Polo contributes to order mitotic exit dephosphorylation events. Cdc14
instructs the sequential pattern of phosphorylation changes, in part through its preferential recognition of serine-based cyclin-dependent
kinase (Cdk) substrates. PP2ACdc55  in turn exhibit a broad substrate spectrum with some selectivity for phospho-threonines. Our results
illustrate synergy and coordination between kinases and phosphatases to orchestrate the phosphoproteome by recognising some specific docking
motifs, phosphoresidus and amino acid regions surrounding the phosphosite.