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XB-ART-44230
Sci Signal 2011 Jun 28;4179:ra42. doi: 10.1126/scisignal.2001796.
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Spatial exclusivity combined with positive and negative selection of phosphorylation motifs is the basis for context-dependent mitotic signaling.

Alexander J , Lim D , Joughin BA , Hegemann B , Hutchins JR , Ehrenberger T , Ivins F , Sessa F , Hudecz O , Nigg EA , Fry AM , Musacchio A , Stukenberg PT , Mechtler K , Peters JM , Smerdon SJ , Yaffe MB .


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The timing and localization of events during mitosis are controlled by the regulated phosphorylation of proteins by the mitotic kinases, which include Aurora A, Aurora B, Nek2 (never in mitosis kinase 2), Plk1 (Polo-like kinase 1), and the cyclin-dependent kinase complex Cdk1/cyclin B. Although mitotic kinases can have overlapping subcellular localizations, each kinase appears to phosphorylate its substrates on distinct sites. To gain insight into the relative importance of local sequence context in kinase selectivity, identify previously unknown substrates of these five mitotic kinases, and explore potential mechanisms for substrate discrimination, we determined the optimal substrate motifs of these major mitotic kinases by positional scanning oriented peptide library screening (PS-OPLS). We verified individual motifs with in vitro peptide kinetic studies and used structural modeling to rationalize the kinase-specific selection of key motif-determining residues at the molecular level. Cross comparisons among the phosphorylation site selectivity motifs of these kinases revealed an evolutionarily conserved mutual exclusion mechanism in which the positively and negatively selected portions of the phosphorylation motifs of mitotic kinases, together with their subcellular localizations, result in proper substrate targeting in a coordinated manner during mitosis.

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Species referenced: Xenopus laevis
Genes referenced: aurka aurkb ccnb1.2 cdk1 nek2 plk1

References [+] :
Ahonen, Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and modulates the association of spindle-checkpoint proteins at kinetochores. 2005, Pubmed, Xenbase