Phosphorylation by Cdk1 induces Plk1-mediated vimentin phosphorylation during mitosis.
Several kinases phosphorylate vimentin, the most common intermediate filament protein, in mitosis. Aurora-B and Rho-kinase regulate vimentin filament separation through the cleavage furrow-specific vimentin phosphorylation. Cdk1 also phosphorylates vimentin from prometaphase to metaphase, but its significance has remained unknown. Here we demonstrated a direct interaction between Plk1 and vimentin-Ser55 phosphorylated by Cdk1, an event that led to Plk1 activation and further vimentin phosphorylation. Plk1 phosphorylated vimentin at approximately 1 mol phosphate/mol substrate, which partly inhibited its filament forming ability, in vitro. Plk1 induced the phosphorylation of vimentin-Ser82, which was elevated from metaphase and maintained until the end of mitosis. This elevation followed the Cdk1-induced vimentin-Ser55 phosphorylation, and was impaired by Plk1 depletion. Mutational analyses revealed that Plk1-induced vimentin-Ser82 phosphorylation plays an important role in vimentin filaments segregation, coordinately with Rho-kinase and Aurora-B. Taken together, these results indicated a novel mechanism that Cdk1 regulated mitotic vimentin phosphorylation via not only a direct enzyme reaction but also Plk1 recruitment to vimentin.
Yamaguchi
Tomoya
T
Division of Biochemistry, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan.
Goto
Hidemasa
H
Yokoyama
Tomoya
T
Silljé
Herman
H
Hanisch
Anja
A
Uldschmid
Andreas
A
Takai
Yasushi
Y
Oguri
Takashi
T
Nigg
Erich A
EA
Inagaki
Masaki
M
D008841:Actin Cytoskeleton / Q000502:physiology; D020816:Amino Acid Motifs; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis; D006801:Humans; D051379:Mice; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012694:Serine; D014746:Vimentin; D020741:rho GTP-Binding Proteins; D000097869:Polo-Like Kinase 1; C576921:AURKB protein, human; C576924:Aurkb protein, mouse