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

• DOI: 10.1126/scisignal.2001796
• Publication Date: 2011-06-28T20:49:11Z
• Authors: Jes Alexander; Daniel Lim; Brian A. Joughin; Björn Hegemann; James R. A. Hutchins; Tobias Ehrenberger; Frank Ivins; Fabio Sessa; Otto Hudecz; Erich A. Nigg; Andrew M. Fry; Andrea Musacchio; P. Todd Stukenberg; Karl Mechtler; Jan-Michael Peters; Stephen J. Smerdon; Michael B. Yaffe
• Keywords: 0301 basic medicine; 571; Amino Acid Motifs; Mitosis; Cell Biology; Protein Serine-Threonine Kinases; Xenopus Proteins; Biochemistry; Evolution, Molecular; Xenopus laevis; 03 medical and health sciences; Peptide Library; Animals; Humans; Phosphorylation; Biologie; Molecular Biology; Signal Transduction

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