to see a detailed, interactive version of this map NOTE: PathFinder requires the Flash plug-in for proper viewing. It will launch in a separate pop-up window, please turn off any pop-up blockers for this web site. Copyright ©2006 ProteinLounge.com

 Mitotic Roles of Polo-like kinase

Polo-like kinases (Plks) are a family of conserved serine/threonine kinases involved in the regulation of cell cycle progression through G2 and M (mitosis). Mammalian polo-like kinases include Plk1 (Xenopus Plx1), Plk2/Snk (Xenopus Plx2), Plk3/Prk/FnK (Xenopus Plx3) and Plk4/Sak. Most species have only one form of Plk; Drosophila (Polo), Schizosaccharomyces pombe (Plo1) and Saccharomyces cerevisiae (Cdc5).

Polo-like kinases are involved in aspects of mitosis that include mitotic entry and exit and cytokinesis. The catalytic domain of polo-like kinases is located in the N-terminus. The C-terminus of Plks contains one or two motifs known as polo boxes that help localize the kinase 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 mediate G2/M transitions, activation of cdc25C and mitotic processes including centrosome maturation, bipolar spindle formation, activation of the anaphase-promoting complex (APC), chromosome segregation, and actin ring formation (cytokinesis).

Plk1 is an early trigger for G2/M transition. Plk1 supports the functional maturation of the centrosome in late G2/early prophase and establishment of the bipolar spindle. Plk1 phosphorylates and activates cdc25C, a phosphatase that dephosphorylates and activates the cyclinB/cdc2 complex. Plk phosphorylates and activates components of the APC. The APC, which is activated by Fizzy-Cdc20 family proteins, is a cell cycle ubiquitin-protein ligase (E3) that degrades mitotic cyclins, chromosomal proteins that maintain cohesion of sister chromatids, and anaphase inhibitors. Abnormal spindle (Asp), a Polo kinase substrate, is a microtubule-associated protein essential for correct behavior of spindle poles and M-phase microtubules. Plk1 localizes to the central region of the spindle in late mitosis and associates with kinesin-like protein CHO1/MKLP1. The homologous motor protein in Drosophila is the pavarotti gene product (PAR).

Plk3 is a multifunctional stress response protein that responses to signals induced by DNA damage and/or mitotic spindle disruption. Plk3 substrates include Chk2 and p53.