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Nat Struct Mol Biol. 2013 Dec;20(12):1415-24. doi: 10.1038/nsmb.2706. Epub 2013 Nov 3.

Multisite phosphorylation networks as signal processors for Cdk1.

Author information

1
Institute of Technology, University of Tartu, Tartu, Estonia.

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.

PMID:
24186061
PMCID:
PMC3855452
DOI:
10.1038/nsmb.2706
[Indexed for MEDLINE]
Free PMC Article

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