Cooperation between mitotic kinesins controls the late stages of cytokinesis.
Cell division is regulated by protein kinases of the Cdk, Polo, and Aurora families. Although it has long been established that temporal control is central to the coordinated action of these kinases, the importance of spatial regulation has only recently been appreciated and is still poorly understood. The kinesin-6 family motor protein MKlp1 is a key regulator of cytokinesis and an ideal substrate for studying spatially regulated protein-phosphorylation events. MKlp1 is negatively regulated by Cdk1 phosphorylation during metaphase and becomes activated in anaphase when cleavage-furrow assembly commences. Aurora B phosphorylates MKlp1 during anaphase and is required for its function in cytokinesis. Another kinesin-6 family motor, MKlp2, mediates the relocation of Aurora B from the centromeres to the central spindle at the onset of anaphase. We now demonstrate that this process is required for the phosphorylation of MKlp1 at S911, an Aurora B consensus site overlapping a bipartite nuclear localization sequence (NLS). MKlp1(S911A) targets to the central spindle but is prematurely imported into the nucleus and fails to support cytokinesis. Spatial restriction of Aurora B to the central spindle by MKlp2 therefore regulates MKlp1 during cytokinesis in human cells.
Neef
Rüdiger
R
Intracellular Protein Transport Group, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Klein
Ulf R
UR
Kopajtich
Robert
R
Barr
Francis A
FA
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference
D017931:DNA Primers; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase