♦ See referenced article, J. Biol. Chem. 2012, 287, 1662–1669
Mitosis, the process by which eukaryotic cells divide and distribute their genetic and organellar contents equally between two daughter cells, is controlled by cyclin-dependent kinases (Cdks). These kinases phosphorylate serine or threonine residues in hundreds of proteins responsible for precisely orchestrating the cell division process. Upon completion of mitosis, Cdks are inactivated, and the sites phosphorylated by them are dephosphorylated. However, how the cell knows when and how to deactivate Cdks and dephosphorylated Cdk targets remains nebulous. Cdc14 phosphatases are thought to be involved. In this Paper of the Week, Harry Charbonneau at Purdue University and colleagues showed that the Cdc14 phosphatase from Saccharomyces cerevisiae has a strong and unexpected preference for phosphoserine over phosphothreonine. Cdc14 is highly conserved in evolution, and the selectivity for phosphoserine is also preserved in all members of the Cdc14 family. The investigators concluded that by discriminating among Cdk phosphorylation sites, “The intrinsic selectivity of Cdc14 may help establish the order of Cdk substrate dephosphorylation during mitotic exit and contribute to roles in other cellular processes.”
Cdc14 selectivity for phosphoserine comes from the structure of the Cdc14 active site.