Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains unexplored. Here we demonstrate that the phosphothreonine preference of PP2A-B55 provides an essential regulatory element of mitotic exit. To allow rapid activation of the anaphase-promoting complex/cyclosome (APC/C) co-activator Cdc20, inhibitory phosphorylation sites are conserved as threonines while serine substitutions delay dephosphorylation and Cdc20 activation. Conversely, to ensure timely activation of the interphase APC/C co-activator Cdh1, inhibitory phosphorylation sites are conserved as serines, and threonine substitutions result in premature Cdh1 activation. Furthermore, rapid translocation of the chromosomal passenger complex to the central spindle is prevented by mutation of a single phosphorylated threonine to serine in inner centromere protein (INCENP), leading to failure of cytokinesis. Altogether, the findings of our work reveal that the inherent residue preference of a protein phosphatase can provide temporal regulation in biological processes.

中文翻译：

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丝氨酸和苏氨酸去磷酸化的不同动力学对于有丝分裂至关重要。

与B55调节亚基复合的蛋白磷酸酶2A（PP2A）逆转有丝分裂出口处的细胞周期蛋白依赖性激酶1（Cdk1）磷酸化。有趣的是，被Cdk1磷酸化的苏氨酸和丝氨酸残基显示出独特的磷酸化动力学，但生物学意义尚待探索。在这里，我们证明PP2A-B55的磷酸苏氨酸偏好性提供了有丝分裂出口的必要调控元件。为了允许后期促进复合物/环体（APC / C）共激活剂Cdc20的快速激活，抑制性磷酸化位点被保留为苏氨酸，而丝氨酸取代则延迟了去磷酸化和Cdc20的激活。相反，为了确保及时激活相间APC / C共激活剂Cdh1，抑制性磷酸化位点被保留为丝氨酸，苏氨酸取代会导致Cdh1过早活化。此外，通过内部着丝粒蛋白（INCENP）中单个磷酸化苏氨酸突变为丝氨酸，可防止染色体乘客复合物快速转运至中心纺锤体，从而导致胞质分裂失败。总而言之，我们工作的发现表明，蛋白质磷酸酶固有的残基偏好性可以在生物过程中提供时间调控。