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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10644 |
| _version_ | 1818019165312647168 |
|---|---|
| author | Anatoly V Zaytsev Dario Segura-Peña Maxim Godzi Abram Calderon Edward R Ballister Rumen Stamatov Alyssa M Mayo Laura Peterson Ben E Black Fazly I Ataullakhanov Michael A Lampson Ekaterina L Grishchuk |
| author_facet | Anatoly V Zaytsev Dario Segura-Peña Maxim Godzi Abram Calderon Edward R Ballister Rumen Stamatov Alyssa M Mayo Laura Peterson Ben E Black Fazly I Ataullakhanov Michael A Lampson Ekaterina L Grishchuk |
| author_sort | Anatoly V Zaytsev |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:48:44Z |
| format | Article |
| id | doaj.art-39837891175341dba3219ee80954e578 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:44Z |
| publishDate | 2016-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-39837891175341dba3219ee80954e5782022-12-22T02:05:15ZengeLife Sciences Publications LtdeLife2050-084X2016-01-01510.7554/eLife.10644Bistability of a coupled Aurora B kinase-phosphatase system in cell divisionAnatoly V Zaytsev0Dario Segura-Peña1Maxim Godzi2Abram Calderon3Edward R Ballister4Rumen Stamatov5Alyssa M Mayo6Laura Peterson7Ben E Black8Fazly I Ataullakhanov9Michael A Lampson10Ekaterina L Grishchuk11https://orcid.org/0000-0002-9504-4270Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biology, University of Pennsylvania, Philadelphia, United StatesDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, RussiaDepartment of Biology, University of Pennsylvania, Philadelphia, United StatesDepartment of Biology, University of Pennsylvania, Philadelphia, United StatesDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biology, University of Pennsylvania, Philadelphia, United StatesDepartment of Biology, Massachusetts Institute of Technology, Cambridge, United States; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesCenter for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia; Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Department of Physics, Moscow State University, Moscow, RussiaDepartment of Biology, University of Pennsylvania, Philadelphia, United StatesDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesAurora 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.https://elifesciences.org/articles/10644kinetochorephosphorylationenzyme kineticsspatio-temporal dynamicsmathematical modelingmitosis |
| spellingShingle | Anatoly V Zaytsev Dario Segura-Peña Maxim Godzi Abram Calderon Edward R Ballister Rumen Stamatov Alyssa M Mayo Laura Peterson Ben E Black Fazly I Ataullakhanov Michael A Lampson Ekaterina L Grishchuk Bistability of a coupled Aurora B kinase-phosphatase system in cell division eLife kinetochore phosphorylation enzyme kinetics spatio-temporal dynamics mathematical modeling mitosis |
| title | Bistability of a coupled Aurora B kinase-phosphatase system in cell division |
| title_full | Bistability of a coupled Aurora B kinase-phosphatase system in cell division |
| title_fullStr | Bistability of a coupled Aurora B kinase-phosphatase system in cell division |
| title_full_unstemmed | Bistability of a coupled Aurora B kinase-phosphatase system in cell division |
| title_short | Bistability of a coupled Aurora B kinase-phosphatase system in cell division |
| title_sort | bistability of a coupled aurora b kinase phosphatase system in cell division |
| topic | kinetochore phosphorylation enzyme kinetics spatio-temporal dynamics mathematical modeling mitosis |
| url | https://elifesciences.org/articles/10644 |
| work_keys_str_mv | AT anatolyvzaytsev bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT dariosegurapena bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT maximgodzi bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT abramcalderon bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT edwardrballister bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT rumenstamatov bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT alyssammayo bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT laurapeterson bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT beneblack bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT fazlyiataullakhanov bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT michaelalampson bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision AT ekaterinalgrishchuk bistabilityofacoupledaurorabkinasephosphatasesystemincelldivision |