title: C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding.
abstract: Cdc25C is a dual-specificity protein kinase that controls entry into mitosis by dephosphorylating Cdc2 on both threonine 14 and tyrosine 15. Cdc25C is phosphorylated on serine 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-TAK1 (for Cdc twenty-five C associated protein kinase) that phosphorylates Cdc25C on serine 216 in vitro. C-TAK1 is ubiquitously expressed in human tissues and cell lines and is distinct from the DNA damage checkpoint kinase Chk1, shown previously to phosphorylate Cdc25C on serine 216. Cotransfection of Cdc25C with C-TAK1 resulted in enhanced phosphorylation of Cdc25C on serine 216. In addition, a physical interaction between C-TAK1 and Cdc25C was observed upon transient overexpression in COS-7 cells. Finally, coproduction of Cdc25C and C-TAK1 in bacteria resulted in the stoichiometric phosphorylation of Cdc25C on serine 216 and facilitated 14-3-3 protein binding in vitro. Taken together, these results suggest that one function of C-TAK1 may be to regulate the interactions between Cdc25C and 14-3-3 in vivo by phosphorylating Cdc25C on serine 216.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Peng
authors.forename: P R
authors.initials: PR
authors.lastname: Graves
authors.forename: S
authors.initials: S
authors.lastname: Ogg
authors.forename: R S
authors.initials: RS
authors.lastname: Thoma
authors.forename: M J
authors.initials: MJ
authors.lastname: Byrnes
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: M T
authors.initials: MT
authors.lastname: Stephenson
authors.forename: H
authors.initials: H
authors.lastname: Piwnica-Worms
mesh_terms: D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase; D020687:cdc25 Phosphatases
chemical_list: D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D011506:Proteins; D012333:RNA, Messenger; D012694:Serine; D014446:Tyrosine 3-Monooxygenase; C111833:MARK3 protein, human; D017346:Protein Serine-Threonine Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases