The Importance of Kinase–Phosphatase Integration: Lessons from Mitosis

• Published in: Trends in cell biology 2018-01, Vol.28 (1), p.6-21
• Main Authors: Gelens, Lendert, Qian, Junbin, Bollen, Mathieu, Saurin, Adrian T.
• Format: Article
• Language: English
• Subjects: Animals; Biological activity; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Chromosome Segregation - genetics; Elongation; Humans; Integration; Kinases; Mitosis; Mitosis - physiology; Phosphatase; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - physiology; Phosphorylation; Protein Kinases - genetics; Protein Kinases - physiology; Signaling; Studies; Substrates
• ISSN: 0962-8924; 1879-3088
• DOI: 10.1016/j.tcb.2017.09.005

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. Although individual phosphorylated molecules often behave like binary switches, multiple copies of each binary switch can be used to output complex biological responses. Kinase and phosphatases work together to shape how these multiple substrate copies behave in time and space. This ‘cooperativity’ is critical for determining three key properties of a signal response: amplitude, localisation, and timing. These properties can be combined to generate complex outputs, such as spatial gradients, biphasic responses and spatial waves. Understanding how kinase and phosphatase activities are integrated is therefore critical for defining how protein phosphorylation signals work.