title: Structure and function of Polo-like kinases.
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.
authors.affiliation: Center for Cancer Research, E18-580, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Lowery
authors.forename: Daniel
authors.initials: D
authors.lastname: Lim
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
mesh_terms: D018797:Cell Cycle Proteins; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1