Polo-like kinase

Polo-like kinases (Plks) are regulatory serine/threonin kinases of the cell cycle involved in mitotic entry, mitotic exit, spindle formation, cytokinesis, and meiosis. Only one Plk is found in the genomes of the fly Drosophila melanogaster (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates and other animals, however, have many Plk family members including Plk1 (Xenopus Plx1), Plk2/Snk (Xenopus Plx2), Plk3/Prk/FnK (Xenopus Plx3), Plk4/Sak and Plk5. Of the vertebrate Plk family members, the mammalian Plk1 has been most extensively studied. During mitosis and cytokinesis, Plks associate with several structures including the centrosome, kinetochores, and the central spindle. The catalytic serine/threonine kinase domain of Plk is at the N-terminus of the polo-like kinase protein. A regulatory domain containing two signature motifs, known as polo box domains, is located at the C-terminus. The polo-box domain (PBD) helps with specificity of substrate and localizes Plk to specific mitotic structures during mitosis. These include the centrosomes in early M phase, the spindle midzone in early and late anaphase and the midbody during cytokinesis. Plks are controlled at the level of protein synthesis and degradation, by the action of upstream kinases and phosphatases, and by localization to specific subcellular structures. Plks are activated by phosphorylation within a short region of the catalytic domain called the T-loop (or activation loop), with several serine/threonine phosphorylation sites in the loop identified. Polo-like kinase kinase 1 (Plkk1) and protein kinase A (PKA) have been shown to be able to phosphorylate Plk1 in vitro. The polo-box domain (PBD) of Plk1 is a phosphopeptide-binding motif. This means that in the absence of a phosphorylated ligand, the PBD interacts with the catalytic domain thereby preventing substrate binding or kinase activation. Occupancy of the PBD by an exogenous phosphopeptide ligand would then cause the release of the catalytic domain, which, together with phosphorylation on the T-loop, converts Plk to the active form.