title: On the molecular mechanisms of mitotic kinase activation.
abstract: During mitosis, human cells exhibit a peak of protein phosphorylation that alters the behaviour of a significant proportion of proteins, driving a dramatic transformation in the cell's shape, intracellular structures and biochemistry. These mitotic phosphorylation events are catalysed by several families of protein kinases, including Auroras, Cdks, Plks, Neks, Bubs, Haspin and Mps1/TTK. The catalytic activities of these kinases are activated by phosphorylation and through protein-protein interactions. In this review, we summarize the current state of knowledge of the structural basis of mitotic kinase activation mechanisms. This review aims to provide a clear and comprehensive primer on these mechanisms to a broad community of researchers, bringing together the common themes, and highlighting specific differences. Along the way, we have uncovered some features of these proteins that have previously gone unreported, and identified unexplored questions for future work. The dysregulation of mitotic kinases is associated with proliferative disorders such as cancer, and structural biology will continue to play a critical role in the development of chemical probes used to interrogate disease biology and applied to the treatment of patients.
authors.affiliation: Department of Biochemistry, Henry Wellcome Laboratories for Structural Biology, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK. richard.bayliss@le.ac.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Bayliss
authors.forename: Andrew
authors.initials: A
authors.lastname: Fry
authors.forename: Tamanna
authors.initials: T
authors.lastname: Haq
authors.forename: Sharon
authors.initials: S
authors.lastname: Yeoh
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008938:Mitosis / Q000235:genetics*; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000201:enzymology* / Q000235:genetics; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D011494:Protein Kinases