Polo-like kinases: structural variations lead to multiple functions

Polo-like kinases (PLKs) are a family of Ser/Thr kinases that have a pivotal role in cell cycle progression, the centrosome cycle, mitosis and cellular responses to DNA damage, which makes them attractive targets for treatments against several diseases.PLK1 is the most ancestral and best-conserved member of the family; it is found in most eukaryotic organisms, except for higher land plants. PLK4 is the most divergent member of the family. PLK2, PLK3 and PLK5 have evolved very recently, probably from a PLK1 gene duplication in vertebrates.PLK1 and PLK4 have distinct structural organizations and are phosphorylated at different residues, which correlate with different mode of actions. The amino-terminal kinase domain and carboxy-terminal polo box domains that characterize PLKs are crucial for regulation of their kinase catalytic activity in time and space, and for controlling subcellular PLK localization.Recent studies show non-canonical functions for PLKs in asymmetric cell division and cilia disassembly.PLKs function in centriole and centrosome biogenesis; PLK1 integrates various external stimuli with cell cycle inputs to coordinate mitotic progression and the centrosome cycle, whereas PLK4 drives centriole assembly.PLK2 and PLK3 have roles in DNA replication and in the DNA damage response and are also expressed in non-proliferative tissues, in which they have a role in cell differentiation and homeostasis (for example, PLK2 and PLK5 regulate neuronal activity).