Kinases and phosphatases work antagonistically to control the behaviour of individual substrate molecules. This can be incorrectly extrapolated to imply that they also work antagonistically on the signals or processes that these molecules control. In fact, in many situations kinases and phosphatases work together to positively drive signal responses. We explain how this ‘cooperativity’ is critical for setting the amplitude, localisation, timing, and shape of phosphorylation signals. We use mitosis to illustrate why these properties are important for controlling mitotic entry, sister chromatid cohesion, kinetochore–microtubule attachments, the spindle assembly checkpoint, mitotic spindle elongation, and mitotic exit. These examples provide a rationale to explain how complex signalling behaviour could rely on similar types of integration within many other biological processes.

激酶和磷酸酶拮抗作用来控制单个底物分子的行为。这可能会被错误地推断为暗示它们还对这些分子控制的信号或过程产生拮抗作用。事实上，在许多情况下，激酶和磷酸酶共同作用，积极驱动信号响应。我们解释了这种“协同性”对于设置磷酸化信号的幅度、定位、时间和形状至关重要。我们使用有丝分裂来说明为什么这些特性对于控制有丝分裂进入、姐妹染色单体内聚、着丝粒-微管附着、纺锤体组装检查点、有丝分裂纺锤体伸长和有丝分裂退出很重要。这些例子提供了一个基本原理来解释复杂的信号传导行为如何依赖于许多其他生物过程中类似类型的整合。