Journal article
A PP2A-B55 recognition signal controls substrate dephosphorylation kinetics during mitotic exit
- Abstract:
- PP2A-B55 is one of the major phosphatases regulating cell division. Despite its importance for temporal control during mitotic exit, how B55 substrates are recognised and differentially dephosphorylated is unclear. Using phosphoproteomics combined with kinetic modelling to extract B55-dependent rate constants, we have systematically identified B55 substrates and assigned their temporal order in mitotic exit. These substrates share a bipartite polybasic recognition determinant (BPR) flanking a Cdk1 phosphorylation-site. Experiments and modelling show that dephosphorylation rate is encoded into B55 substrates, including its inhibitor ENSA, by cooperative action of basic residues within the BPR. A complementary acidic surface on B55 decodes this signal, supporting a cooperative electrostatic mechanism for substrate selection. A further level of specificity is encoded into B55 substrates, since B55 displays selectivity for phosphothreonine. These simple biochemical properties, combined with feedback control of B55 activity by the phosphoserine-containing substrate/inhibitor ENSA can help explain the temporal sequence of events during exit from mitosis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.9MB, Terms of use)
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- Publisher copy:
- 10.1083/jcb.201606033
Authors
+ Biotechnological and Biological Sciences Research
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- Funding agency for:
- Novak, B
- Grant:
- BB/M00354X/1
+ Engineering and Physical Sciences Research Council
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- Funding agency for:
- Hutter, L
- Grant:
- EPG03706X/1
- Publisher:
- Rockefeller University Press
- Journal:
- Journal of Cell Biology More from this journal
- Publication date:
- 2016-08-22
- Acceptance date:
- 2016-07-13
- DOI:
- EISSN:
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1540-8140
- ISSN:
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0021-9525
- Keywords:
- Pubs id:
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pubs:637868
- UUID:
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uuid:c211d4a1-c4bf-486d-891a-567458695ca8
- Local pid:
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pubs:637868
- Source identifiers:
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637868
- Deposit date:
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2016-08-08
- ARK identifier:
Terms of use
- Copyright holder:
- Cundell, et al
- Copyright date:
- 2016
- Notes:
- © 2016 Cundell et al. This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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