Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast.
Simultaneous inactivation of pyp1 and pyp2 PTPases in fission yeast leads to aberrant cell morphology and growth arrest. Spontaneous recessive mutations that bypass the requirement for pyp1 and pyp2 and reside in two complementation groups were isolated, sty1 and sty2. sty1- and sty2- mutant cells are substantially delayed in the timing of mitotic initiation. We have isolated the sty1 gene, which encodes a MAP kinase that is closely related to a subfamily of MAP kinases regulated by osmotic stress including Saccharomyces cervisiae HOG1 and human CSBP1. We find that sty2 is allelic to the wis1 MAP kinase kinase and that delta sty1 and delta wis1 cells are unable to grow in high osmolarity medium. Osmotic stress induces both tyrosine phosphorylation of Sty1 and a reduction in cell size at division. Pyp2 associates with and tyrosine dephosphorylates Sty1 in vitro. We find that wis1-dependent induction of pyp2 mRNA is responsible for tyrosine dephosphorylation of Sty1 in vivo on prolonged exposure to osmotic stress. We conclude that Pyp1 and Pyp2 are tyrosine-specific MAP kinase phosphatases that inactivate an osmoregulated MAP kinase, Sty1, which acts downstream of the Wis1 MAP kinase kinase to control cell size at division in fission yeast.
Millar
J B
JB
Division of Yeast Genetics, National Institute for Medical Research, Ridgeway, London, UK.
Buck
V
V
Wilkinson
M G
MG
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D004790:Enzyme Induction; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009994:Osmolar Concentration; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D014443:Tyrosine / Q000378:metabolism
D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; D014443:Tyrosine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases; C072068:wis1 protein, S pombe; D017027:Protein Tyrosine Phosphatases; C078759:pyp2 protein, S pombe