title: Multisite phosphorylation networks as signal processors for Cdk1.
abstract: The order and timing of cell-cycle events is controlled by changing substrate specificity and different activity thresholds of cyclin-dependent kinases (CDKs). However, it is not understood how a single protein kinase can trigger hundreds of switches in a sufficiently time-resolved fashion. We show that cyclin-Cdk1-Cks1-dependent phosphorylation of multisite targets in Saccharomyces cerevisiae is controlled by key substrate parameters including distances between phosphorylation sites, distribution of serines and threonines as phosphoacceptors and positioning of cyclin-docking motifs. The component mediating the key interactions in this process is Cks1, the phosphoadaptor subunit of the cyclin-Cdk1-Cks1 complex. We propose that variation of these parameters within networks of phosphorylation sites in different targets provides a wide range of possibilities for differential amplification of Cdk1 signals, thus providing a mechanism to generate a wide range of thresholds in the cell cycle.
authors.affiliation: Institute of Technology, University of Tartu, Tartu, Estonia.
authors.forename: Mardo
authors.initials: M
authors.lastname: Kõivomägi
authors.forename: Mihkel
authors.initials: M
authors.lastname: Ord
authors.forename: Anna
authors.initials: A
authors.lastname: Iofik
authors.forename: Ervin
authors.initials: E
authors.lastname: Valk
authors.forename: Rainis
authors.initials: R
authors.lastname: Venta
authors.forename: Ilona
authors.initials: I
authors.lastname: Faustova
authors.forename: Rait
authors.initials: R
authors.lastname: Kivi
authors.forename: Eva Rose M
authors.initials: ER
authors.lastname: Balog
authors.forename: Seth M
authors.initials: SM
authors.lastname: Rubin
authors.forename: Mart
authors.initials: M
authors.lastname: Loog
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D019926:Cyclin B / Q000378:metabolism / Q000502:physiology; D016213:Cyclins / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry / Q000378:metabolism; D010769:Phosphothreonine / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081185:CKS1 protein, S cerevisiae; C076558:CLB5 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D016213:Cyclins; D029701:Saccharomyces cerevisiae Proteins; D010769:Phosphothreonine; D010768:Phosphoserine; D016203:CDC2 Protein Kinase