title: H₂O₂ stress-specific regulation of S. pombe MAPK Sty1 by mitochondrial protein phosphatase Ptc4.
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.
authors.affiliation: Cell Regulation Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Di
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Holmes
authors.forename: Amna
authors.initials: A
authors.lastname: Butt
authors.forename: Keren
authors.initials: K
authors.lastname: Dawson
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Mironov
authors.forename: Vassilios N
authors.initials: VN
authors.lastname: Kotiadis
authors.forename: Campbell W
authors.initials: CW
authors.lastname: Gourlay
authors.forename: Nic
authors.initials: N
authors.lastname: Jones
authors.forename: Caroline R M
authors.initials: CR
authors.lastname: Wilkinson
mesh_terms: D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D059748:Proteolysis; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D010749:Phosphoprotein Phosphatases