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Structure and function of Polo-like kinases

Oncogene volume 24, pages 248–259 (2005)Cite this article

Abstract

Polo-like kinases play critical roles during multiple stages of cell cycle progression. All Polo-like kinases contain an N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that contains one or two Polo-boxes. For Polo-like kinase 1, 2, and 3, and their homologs, the entire C-terminal region, including both Polo-boxes, functions as a single modular phosphoserine/threonine-binding domain known as the Polo-box domain (PBD). In the absence of a bound substrate, the PBD inhibits the basal activity of the kinase domain. Phosphorylation-dependent binding of the PBD to its ligands releases the kinase domain, while simultaneously localizing Polo-like kinases to specific subcellular structures. These observations suggest two different models for how the PBD integrates signals arising from other mitotic kinases to target the activated kinase towards distinct substrates. The recent X-ray crystal structures of the PBD provide insights into the structural basis for PBD function and kinase regulation. Molecular modelling of the structure of the isolated kinase domain reveals a potential basis for motif-dependent substrate specificity.

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Acknowledgements

We are grateful to Drs Louise N Johnson, Erich A Nigg, Frank Sicheri, Peter Rellos, and Stephen J Smerdon for discussions and insight into Plk structure and function. DML is supported by a Howard Hughes Medical Institute Predoctoral Fellowship. DL is supported by a Jane Coffin Childs Memorial Fellowship. This work was supported by NIH Grant GM60594 and a Burroughs-Wellcome Career Development Award to MBY.

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    Drew M Lowery, Daniel Lim & Michael B Yaffe

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Lowery, D., Lim, D. & Yaffe, M. Structure and function of Polo-like kinases. Oncogene 24, 248–259 (2005). https://doi.org/10.1038/sj.onc.1208280

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