Research ArticleMitotic Kinases

Spatial Exclusivity Combined with Positive and Negative Selection of Phosphorylation Motifs Is the Basis for Context-Dependent Mitotic Signaling

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Science Signaling  28 Jun 2011:
Vol. 4, Issue 179, pp. ra42
DOI: 10.1126/scisignal.2001796

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Motifs and Antimotifs

Mitosis is a complex process controlled by multiple kinases, such as the cyclin-dependent kinase Cdk1/cyclin B, the Aurora kinases Aurora A and B, the kinase Nek2, and the Polo-like kinases, especially Plk1 (Polo-like kinase 1). Alexander et al. used in vitro assays and a peptide library screening method to refine the phosphorylation site selectivity of each of these kinases and found that those that were located in similar compartments within the cell during mitosis showed a strong negative selection for residues that were positively selected by other kinases in the same compartment. In contrast, those that were located in distinct compartments tended to recognize similar phosphorylation site motifs. These results led the authors to propose that mitotic kinase selectivity is determined by two factors—spatial exclusivity and “antimotif” specificity.