H2O2 stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4.
dc.contributor.author | Di, Yujun | |
dc.contributor.author | Holmes, Emily J | |
dc.contributor.author | Butt, Amna | |
dc.contributor.author | Dawson, Keren | |
dc.contributor.author | Mironov, A | |
dc.contributor.author | Kotiadis, V N | |
dc.contributor.author | Gourlay, C W | |
dc.contributor.author | Jones, Nic | |
dc.contributor.author | Wilkinson, Caroline R M | |
dc.date.accessioned | 2012-03-22T13:14:59Z | |
dc.date.available | 2012-03-22T13:14:59Z | |
dc.date.issued | 2012-02-01 | |
dc.identifier.citation | H2O2 stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4. 2012, 31 (3):563-75 EMBO J. | en_GB |
dc.identifier.issn | 1460-2075 | |
dc.identifier.pmid | 22139357 | |
dc.identifier.doi | 10.1038/emboj.2011.438 | |
dc.identifier.uri | http://hdl.handle.net/10541/216289 | |
dc.description.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 H(2)O(2) 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 H(2)O(2), 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. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to The EMBO journal | en_GB |
dc.subject.mesh | Hydrogen Peroxide | |
dc.subject.mesh | Mitochondria | |
dc.subject.mesh | Mitogen-Activated Protein Kinases | |
dc.subject.mesh | Phosphoprotein Phosphatases | |
dc.subject.mesh | Schizosaccharomyces pombe Proteins | |
dc.title | H2O2 stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4. | en |
dc.type | Article | en |
dc.contributor.department | Cell Regulation Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK. | en_GB |
dc.identifier.journal | EMBO Journal | en_GB |
html.description.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 H(2)O(2) 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 H(2)O(2), 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. |