Pyp3 PTPase acts as a mitotic inducer in fission yeast.
The p34cdc2 M-phase kinase is regulated by inhibitory phosphorylation of Tyr15, largely through the actions of the p107wee1 tyrosine kinase and p80cdc25 protein tyrosine phosphatase (PTPase). In this study we demonstrate that a second PTPase, encoded by pyp3, also contributes to tyrosyl dephosphorylation of p34cdc2. Pyp3 was identified as a high copy suppressor of a cdc25- mutation. The pyp3 gene encodes a 33 kDa PTPase that is more closely related to human PTP1B and fission yeast pyp1 and pyp2 PTPases than to cdc25. Pyp3 does not share an essential overlapping function with pyp1 or pyp2. We demonstrate that disruption of pyp3 causes a mitotic delay that is greatly exacerbated in cells that are partially defective for cdc25 function and that pyp3 function is essential in cdc25-disruption wee1- strains. Pyp3 PTPase effectively dephosphorylates and activates the p34cdc2 kinase in vitro. We conclude that the pyp3 PTPase acts cooperatively with p80cdc25 to dephosphorylate Tyr15 of p34cdc2.
Millar
J B
JB
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Lenaers
G
G
Russell
P
P
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016153:Genes, Suppressor; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D020666:ras-GRF1
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1; D011494:Protein Kinases; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C078757:pyp3 protein, S pombe; D017027:Protein Tyrosine Phosphatases