The structural mechanisms that underpin mitotic kinase activation

Charlotte A. Dodson, Tamanna Haq, Sharon Yeoh, Andrew M. Fry, Richard Bayliss

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

In eukaryotic cells, the peak of protein phosphorylation occurs during mitosis, switching the activities of a significant proportion of proteins and orchestrating a wholesale reorganization of cell shape and internal architecture. Most mitotic protein phosphorylation events are catalysed by a small subset of serine/threonine protein kinases. These include members of the Cdk (cyclin-dependent kinase), Plk (Polo-like kinase), Aurora, Nek (NimA-related kinase) and Bub families, as well as Haspin, Greatwall and Mps1/TTK. There has been steady progress in resolving the structural mechanisms that regulate the catalytic activities of these mitotic kinases. From structural and biochemical perspectives, kinase activation appears not as a binary process (from inactive to active), but as a series of states that exhibit varying degrees of activity. In its lowest activity state, a mitotic kinase may exhibit diverse autoinhibited or inactive conformations. Kinase activation proceeds via phosphorylation and/or association with a binding partner. These remodel the structure into an active conformation that is common to almost all protein kinases. However, all mitotic kinases of known structure have divergent features, many of which are key to understanding their specific regulatory mechanisms. Finally, mitotic kinases are an important class of drug target, and their structural characterization has facilitated the rational design of chemical inhibitors.
Original languageEnglish
Pages (from-to)1037-1041
JournalBiochemical Society Transactions
Volume41
Issue number4
DOIs
Publication statusPublished - 18 Jul 2013

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Phosphotransferases
Chemical activation
Phosphorylation
Conformations
Aurora Kinases
Proteins
Cyclin-Dependent Kinases
Cell Shape
Protein-Serine-Threonine Kinases
Eukaryotic Cells
Mitosis
Protein Kinases
Catalyst activity
Association reactions
Pharmaceutical Preparations

Cite this

The structural mechanisms that underpin mitotic kinase activation. / Dodson, Charlotte A.; Haq, Tamanna; Yeoh, Sharon; Fry, Andrew M.; Bayliss, Richard.

In: Biochemical Society Transactions, Vol. 41, No. 4, 18.07.2013, p. 1037-1041.

Research output: Contribution to journalReview article

Dodson, Charlotte A. ; Haq, Tamanna ; Yeoh, Sharon ; Fry, Andrew M. ; Bayliss, Richard. / The structural mechanisms that underpin mitotic kinase activation. In: Biochemical Society Transactions. 2013 ; Vol. 41, No. 4. pp. 1037-1041.
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