C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding

Cdc25C is a dual-specificfty protein kinase that controls entry into mitosis by dephosphorylating Cdc2 on both threonine 14 and tyrosine 15. cdc25c is phosphorylated on sorine 216 throughout interphase but not during mitosis. Serine 216 phosphorylation mediates the binding of 14-3-3 protein to cdc25C, and Cdc25C/14-3-3 complexes are present throughout interphase but not during mitosis. Here we report the cloning of a human kinase denoted c-TAKIfordc twenty-five Cssociated protein jcinase) that phosphorylates Cdc25C on serine 216 In vitro. C-TAKI Is ubiquitously expressed in human tissues and cell lines and is distinct from the DNA damage checkpoint kinase Chkl , shown previously to phosphorylate Cdc25C on serine 216. Cotransfectlon of Cdc25C with C-TAKI resulted In enhanced phosphorylation of Cdc25C on serine 216. In addition, a physical interaction between C-TAKI and Cdc25C was observed upon transient overexpression in COS-7 cells. Finally, coproduction of Cdc25C and c-TAKI in bacteria resulted in the stoichiometric phosphorylation of Cdc25C on serine 216 and facilitated 14-3-3 protein binding in vitm. Taken together, these results suggest that one function of c-TAKI may be to regulate the interactions between Cdc25C and 14-3-3 in vivo by phosphorylating Cdc25C on serine 216.