C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding.
C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding.
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发表时间：
1998-03
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通讯作者：
C. Peng;P. Graves;S. Ogg;R. Thoma;M. J. Byrnes;Zhiqi Wu;Mary T. Stephenson;H. Piwnica-Worms
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作者：
C. Peng;P. Graves;S. Ogg;R. Thoma;M. J. Byrnes;Zhiqi Wu;Mary T. Stephenson;H. Piwnica-Worms
Cdc 25 C是一种双特异性蛋白激酶，通过使苏氨酸14和酪氨酸15上的Cdc 2去磷酸化来控制进入有丝分裂。Cdc 25 C在整个间期的丝氨酸216上磷酸化，但在有丝分裂期间不磷酸化。丝氨酸216磷酸化介导14-3-3蛋白与Cdc 25 C的结合，Cdc 25 C/14-3-3复合物存在于整个间期，但不在有丝分裂期间。在这里，我们报告的克隆的人激酶表示C-TAK 1（为Cdc 25 C相关蛋白激酶），磷酸化Cdc 25 C丝氨酸216在体外。C-TAK 1在人类组织和细胞系中广泛表达，与DNA损伤检查点激酶Chk 1不同，Chk 1先前显示磷酸化丝氨酸216上的Cdc 25 C。Cdc 25 C与C-TAK 1共转染导致Cdc 25 C在丝氨酸216上的磷酸化增强。此外，C-TAK 1和Cdc 25 C之间的物理相互作用后，观察到短暂的过度表达在COS-7细胞。最后，Cdc 25 C和C-TAK 1在细菌中的共同生产导致了Cdc 25 C在丝氨酸216上的化学计量磷酸化，并促进了14-3-3蛋白的体外结合。综上所述，这些结果表明，C-TAK 1的功能之一可能是调节Cdc 25 C和14-3-3之间的相互作用在体内通过磷酸化Cdc 25 C丝氨酸216。
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.