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

  1. Anatoly V Zaytsev
  2. Dario Segura-Peña
  3. Maxim Godzi
  4. Abram Calderon
  5. Edward R Ballister
  6. Rumen Stamatov
  7. Alyssa M Mayo
  8. Laura Peterson
  9. Ben E Black
  10. Fazly I Ataullakhanov
  11. Michael A Lampson
  12. Ekaterina L Grishchuk  Is a corresponding author
  1. University of Pennsylvania, United States
  2. Massachusetts Institute of Technology, United States
  3. Russian Academy of Sciences, Russia

Abstract

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.

Article and author information

Author details

  1. Anatoly V Zaytsev

    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dario Segura-Peña

    Department of Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Maxim Godzi

    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Abram Calderon

    Department of Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Edward R Ballister

    Department of Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Rumen Stamatov

    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Alyssa M Mayo

    Department of Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Laura Peterson

    Department of Biology, Department of Chemistry, Massachusetts Institute of Technology, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ben E Black

    Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Fazly I Ataullakhanov

    Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
    Competing interests
    The authors declare that no competing interests exist.
  11. Michael A Lampson

    Department of Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Ekaterina L Grishchuk

    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    For correspondence
    gekate@mail.med.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2016, Zaytsev et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Anatoly V Zaytsev
  2. Dario Segura-Peña
  3. Maxim Godzi
  4. Abram Calderon
  5. Edward R Ballister
  6. Rumen Stamatov
  7. Alyssa M Mayo
  8. Laura Peterson
  9. Ben E Black
  10. Fazly I Ataullakhanov
  11. Michael A Lampson
  12. Ekaterina L Grishchuk
(2016)
Bistability of a coupled Aurora B kinase-phosphatase system in cell division
eLife 5:e10644.
https://doi.org/10.7554/eLife.10644

Share this article

https://doi.org/10.7554/eLife.10644

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