title: Negative regulation of mitosis in fission yeast by catalytically inactive pyp1 and pyp2 mutants.
abstract: The Schizosaccharomyces pombe genes pyp1+ and pyp2+ encode protein tyrosine phosphatases (PTPases) that act as negative regulators of mitosis upstream of the wee1+/mik1+ pathway. Here we provide evidence that pyp1+ and pyp2+ function independently of cdr1+(nim1+) in the inhibition of mitosis and that the wee1 kinase is not a direct substrate of either PTPase. In a pyp1::ura4 cdc25-22 genetic background, overexpression of either the N-terminal domain of pyp1+ or a catalytically inactive mutant, pyp1C470S, causes cell cycle arrest. This phenotype reverses the suppression of a cdc25 temperature-sensitive mutation at 35 degrees C caused by a pyp1 disruption. Furthermore, pyp1C470S and a catalytically inactive mutant of pyp2, pyp2C630S, induce mitotic delay as do their wild-type counterparts. Analysis of pyp1+ and pyp2+ further reveals that in vitro PTPase activity of pyp1 and pyp2, as well as their biological activity, is dependent on the presence of N-terminal sequences that are not normally considered part of PTPase catalytic domains.
authors.affiliation: Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138.
authors.forename: G
authors.initials: G
authors.lastname: Hannig
authors.forename: S
authors.initials: S
authors.lastname: Ottilie
authors.forename: R L
authors.initials: RL
authors.lastname: Erikson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003545:Cysteine; D004926:Escherichia coli; D015870:Gene Expression; D008938:Mitosis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics*; D012694:Serine
chemical_list: D009838:Oligodeoxyribonucleotides; D012694:Serine; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine