Bistability of a coupled Aurora B kinase-phosphatase system in cell division

Aurora B kinase, a key regulator of cell division, localizes to specific cellular locations, but the regulatory mechanisms responsible for phosphorylation of substrates located remotely from kinase enrichment sites are unclear. Here, we provide evidence that this activity at a distance depends on bo...

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Bibliographic Details
Published in:eLife 2016-01, Vol.5, p.e10644-e10644
Main Authors: Zaytsev, Anatoly V, Segura-Peña, Dario, Godzi, Maxim, Calderon, Abram, Ballister, Edward R, Stamatov, Rumen, Mayo, Alyssa M, Peterson, Laura, Black, Ben E, Ataullakhanov, Fazly I, Lampson, Michael A, Grishchuk, Ekaterina L
Format: Article
Language:English
Subjects:
Aurora B protein
Aurora Kinase B - metabolism
Cell Biology
Cell Cycle Proteins - metabolism
Cell Division
Centromere - metabolism
Chromosomes
Computational and Systems Biology
enzyme kinetics
Epithelial Cells - enzymology
Epithelial Cells - physiology
Experiments
Fluorescence resonance energy transfer
HeLa Cells
Humans
Kinases
kinetochore
Localization
mathematical modeling
Medical research
Microscopy
Microtubules - metabolism
mitosis
Observations
Optical Imaging
Phosphoric Monoester Hydrolases - metabolism
Phosphorylation
Phosphotransferases
Physiological aspects
Sensors
spatio-temporal dynamics
Spindle Apparatus - metabolism
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Summary:Aurora B kinase, a key regulator of cell division, localizes to specific cellular locations, but the regulatory mechanisms responsible for phosphorylation of substrates located remotely from kinase enrichment sites are unclear. Here, we provide evidence that this activity at a distance depends on both sites of high kinase concentration and the bistability of a coupled kinase-phosphatase system. We reconstitute this bistable behavior and hysteresis using purified components to reveal co-existence of distinct high and low Aurora B activity states, sustained by a two-component kinase autoactivation mechanism. Furthermore, we demonstrate these non-linear regimes in live cells using a FRET-based phosphorylation sensor, and provide a mechanistic theoretical model for spatial regulation of Aurora B phosphorylation. We propose that bistability of an Aurora B-phosphatase system underlies formation of spatial phosphorylation patterns, which are generated and spread from sites of kinase autoactivation, thereby regulating cell division.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.10644