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H 2 O 2 stress‐specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4
Author(s) -
Di Yujun,
Holmes Emily J,
Butt Amna,
Dawson Keren,
Mironov Aleksandr,
Kotiadis Vassilios N,
Gourlay Campbell W,
Jones Nic,
Wilkinson Caroline R M
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.438
Subject(s) - phosphatase , mapk/erk pathway , schizosaccharomyces pombe , mitochondrion , microbiology and biotechnology , dusp6 , biology , kinase , phosphorylation , protein tyrosine phosphatase , biochemistry , yeast , protein phosphatase 2 , saccharomyces cerevisiae
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.