Aurora-B associated protein phosphatases as negative regulators of kinase activation.
The human serine/threonine kinase Aurora-B is structurally related to the protein kinase Ipl1p from S cerevisiae and aurora from Drosophila melanogaster, which are key regulators of mitosis. The present study shows that human Aurora-B is activated by okadaic acid and forms complexes with the protein serine/threonine phosphatase type 1 (PP1) or PP2A, but not with PP5. These data identified Aurora-B associated protein phosphatases as negative regulators of kinase activation. We then used a series of substrates based on a histone H3 phosphorylation site (residues 5-15) to determine the substrate specificity of human Aurora-B. We found that this enzyme is an arginine-directed kinase that can phosphorylate histone H3 at serines 10 and 28 in vitro, suggesting that human Aurora-B is a mitotic histone H3 kinase.
Sugiyama
Keiichi
K
Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya 466-0065, Japan.
Sugiura
Kazumitsu
K
Hara
Tomohiro
T
Sugimoto
Kenji
K
Shima
Hiroshi
H
Honda
Kei
K
Furukawa
Koichi
K
Yamashita
Shunichi
S
Urano
Takeshi
T
D000818:Animals; D001120:Arginine / Q000737:chemistry; D064107:Aurora Kinase B; D064127:Aurora Kinases; D019556:COS Cells; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity
D006657:Histones; D007527:Isoenzymes; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D019319:Okadaic Acid; D001120:Arginine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5