PP1 and PP2A Use Opposite Phospho-dependencies to Control Distinct Processes at the Kinetochore.
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Embargo End Date
ICR Authors
Authors
Smith, RJ
Cordeiro, MH
Davey, NE
Vallardi, G
Ciliberto, A
Gross, F
Saurin, AT
Cordeiro, MH
Davey, NE
Vallardi, G
Ciliberto, A
Gross, F
Saurin, AT
Document Type
Journal Article
Date
2019-08-20
Date Accepted
2019-07-18
Abstract
PP1 and PP2A-B56 are major serine/threonine phosphatase families that achieve specificity by colocalizing with substrates. At the kinetochore, however, both phosphatases localize to an almost identical molecular space and yet they still manage to regulate unique pathways and processes. By switching or modulating the positions of PP1/PP2A-B56 at kinetochores, we show that their unique downstream effects are not due to either the identity of the phosphatase or its precise location. Instead, these phosphatases signal differently because their kinetochore recruitment can be either inhibited (PP1) or enhanced (PP2A) by phosphorylation inputs. Mathematical modeling explains how these inverse phospho-dependencies elicit unique forms of cross-regulation and feedback, which allows otherwise indistinguishable phosphatases to produce distinct network behaviors and control different mitotic processes. Furthermore, our genome-wide analysis suggests that these major phosphatase families may have evolved to respond to phosphorylation inputs in opposite ways because many other PP1 and PP2A-B56-binding motifs are also phospho-regulated.
Citation
Cell reports, 2019, 28 (8), pp. 2206 - 2219.e8
Source Title
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247