Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a.
The microtubule depolymerase Kif2a controls spindle assembly and dynamics and is essential for chromosome congression and segregation. Through a proteomic analysis, we identified Kif2a as a target for regulation by the Polo-like kinase Plk1. Plk1 interacts with Kif2a, but only in mitosis, in a manner dependent on its kinase activity. Plk1 phosphorylates Kif2a and enhances its depolymerase activity in vitro. Inhibition or depletion of Plk1 decreases microtubule-associated Kif2a signals and increases the spindle microtubule intensity in vivo. Interestingly, Aurora A also interacts with and phosphorylates Kif2a. Phosphorylation of Kif2a by Aurora A suppresses its depolymerase activity in vitro, and inhibition of Aurora A increases the microtubule-associated Kif2a signals and reduces the spindle microtubule intensity in vivo. Thus, Kif2a is regulated positively by Plk1 and negatively by Aurora A. We propose that this antagonistic regulation confers differential stability to microtubules in the spindle versus at the pole versus in the cytosol, and that this spatial differential stability is important for spindle assembly and function.
Jang
Chang-Young
CY
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Coppinger
Judith A
JA
Seki
Akiko
A
Yates
John R
JR
Fang
Guowei
G
D000595:Amino Acid Sequence; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D000097869:Polo-Like Kinase 1; C509805:KIF2A protein, human