title: Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells.
abstract: Mitosis is a process involving a complex series of events that require careful coordination. Protein phosphorylation by a small number of kinases, in particular Aurora A, Aurora B, the cyclin-dependent kinase-cyclin complex Cdk1/cyclinB, and Polo-like kinase 1 (Plk1), orchestrates almost every step of cell division, from entry into mitosis to cytokinesis. To discover more about the functions of Aurora A, Aurora B, and kinases of the Plk family, we mapped mitotic phosphorylation sites to these kinases through the combined use of quantitative phosphoproteomics and selective targeting of kinase activities by small-molecule inhibitors. Using this integrated approach, we connected 778 phosphorylation sites on 562 proteins with these enzymes in cells arrested in mitosis. By connecting the kinases to protein complexes, we associated these kinases with functional modules. In addition to predicting previously unknown functions, this work establishes additional substrate-recognition motifs for these kinases and provides an analytical template for further use in dissecting kinase signaling events in other areas of cellular signaling and systems biology.
authors.affiliation: Department of Genetics, Dartmouth Medical School, Lebanon, NH 03756, USA.
authors.forename: Arminja N
authors.initials: AN
authors.lastname: Kettenbach
authors.forename: Devin K
authors.initials: DK
authors.lastname: Schweppe
authors.forename: Brendan K
authors.initials: BK
authors.lastname: Faherty
authors.forename: Dov
authors.initials: D
authors.lastname: Pechenick
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Pletnev
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
mesh_terms: D020816:Amino Acid Motifs; D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000097869:Polo-Like Kinase 1
chemical_list: D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D019926:Cyclin B; D017346:Protein Serine-Threonine Kinases; D020543:Proteome; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C576921:AURKB protein, human