title: PP2ACdc55Phosphatase Imposes Ordered Cell-Cycle Phosphorylation by Opposing Threonine Phosphorylation.
abstract: In the quantitative model of cell-cycle control, progression from G1 through S phase and into mitosis is ordered by thresholds of increasing cyclin-dependent kinase (Cdk) activity. How such thresholds are read out by substrates that respond with the correct phosphorylation timing is not known. Here, using the budding yeast model, we show that the abundant PP2ACdc55phosphatase counteracts Cdk phosphorylation during interphase and delays phosphorylation of late Cdk substrates. PP2ACdc55specifically counteracts phosphorylation on threonine residues, and consequently, we find that threonine-directed phosphorylation occurs late in the cell cycle. Furthermore, the late phosphorylation of a model substrate, Ndd1, depends on threonine identity of its Cdk target sites. Our results support a model in which Cdk-counteracting phosphatases contribute to cell-cycle ordering by imposing Cdk thresholds. They also unveil a regulatory principle based on the phosphoacceptor amino acid, which is likely to apply to signaling pathways beyond cell-cycle control.
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Molly
authors.initials: M
authors.lastname: Godfrey
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Touati
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Meghna
authors.initials: M
authors.lastname: Kataria
authors.affiliation: Mass Spectrometry Proteomics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jones
authors.affiliation: Mass Spectrometry Proteomics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, London NW1 1AT, UK. Electronic address: frank.uhlmann@crick.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; C118820:NDD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D013912:Threonine; D012694:Serine; D018844:Cyclin-Dependent Kinases; D054648:Protein Phosphatase 2
keywords: PP2A phosphatase; Saccharomyces cerevisiae; cell cycle; cyclin-dependent kinase; phosphoproteome analysis