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H2O2 stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4

Di, Yujun, Holmes, Emily J, Butt, Amna, Dawson, Keren, Mironov, Aleksandr, Kotiadis, Vassilios N, Gourlay, Campbell W., Jones, Nic, Wilkinson, Caroline R M (2011) H2O2 stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4. The EMBO Journal, 31 (3). pp. 563-575. ISSN 0261-4189. (doi:10.1038/emboj.2011.438) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1038/emboj.2011.438

Abstract

In fission yeast, the stress?activated MAP kinase, Sty1, is activated via phosphorylation upon exposure to stress and orchestrates an appropriate response. Its activity is attenuated by either serine/threonine PP2C or tyrosine phosphatases. Here, we found that the PP2C phosphatase, Ptc4, plays an important role in inactivating Sty1 specifically upon oxidative stress. Sty1 activity remains high in a ptc4 deletion mutant upon H2O2 but not under other types of stress. Surprisingly, Ptc4 localizes to the mitochondria and is targeted there by an N?terminal mitochondrial targeting sequence (MTS), which is cleaved upon import. A fraction of Sty1 also localizes to the mitochondria suggesting that Ptc4 attenuates the activity of a mitochondrial pool of this MAPK. Cleavage of the Ptc4 MTS is greatly reduced specifically upon H2O2, resulting in the full?length form of the phosphatase; this displays a stronger interaction with Sty1, thus suggesting a novel mechanism by which the negative regulation of MAPK signalling is controlled and providing an explanation for the oxidative stress?specific nature of the regulation of Sty1 by Ptc4.

Item Type: Article
DOI/Identification number: 10.1038/emboj.2011.438
Uncontrolled keywords: MAP Kinase SignallingMitochondriaPtc4S. PombeSty1
Subjects: Q Science
Q Science > Q Science (General)
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Campbell Gourlay
Date Deposited: 08 Dec 2017 10:07 UTC
Last Modified: 29 May 2019 10:17 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34265 (The current URI for this page, for reference purposes)
Gourlay, Campbell W.: https://orcid.org/0000-0002-2373-6788
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