title: Control of Sty1 MAPK activity through stabilisation of the Pyp2 MAPK phosphatase.
abstract: In all eukaryotes tight control of mitogen-activated protein kinase (MAPK) activity plays an important role in modulating intracellular signalling in response to changing environments. The fission yeast MAPK Sty1 (also known as Spc1 or Phh1) is highly activated in response to a variety of external stresses. To avoid segregation of damaged organelles or chromosomes, strong Sty1 activation transiently blocks mitosis and cell division until such stresses have been dealt with. MAPK phosphatases dephosphorylate Sty1 to reduce kinase activity. Therefore, tight control of MAPK phosphatases is central for stress adaptation and for cell division to resume. In contrast to Pyp1, the fission yeast Pyp2 MAPK phosphatase is under environmental control. Pyp2 has a unique sequence (the linker region) between the catalytic domain and the N-terminal MAPK-binding site. Here we show that the Pyp2 linker region is a destabilisation domain. Furthermore, the linker region is highly phosphorylated to increase Pyp2 protein stability and this phosphorylation is Sty1 dependent. Our data suggests that Sty1 activation promotes Pyp2 phosphorylation to increase the stability of the phosphatase. This MAPK-dependent Pyp2 stabilisation allows cells to attenuate MAPK signalling and resume cell division, once stresses have been dealt with.
authors.affiliation: University of Manchester, Faculty of Life Sciences, C.4255 Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Kowalczyk
authors.forename: Sonya
authors.initials: S
authors.lastname: Hartmuth
authors.forename: David
authors.initials: D
authors.lastname: Perera
authors.forename: Peter
authors.initials: P
authors.lastname: Stansfield
authors.forename: Janni
authors.initials: J
authors.lastname: Petersen
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D017027:Protein Tyrosine Phosphatases; C078759:pyp2 protein, S pombe
keywords: DUSP6; MAPK; Phosphatase; Pyp2; Schizosaccharomyces pombe; Sty1