Aurora-B associated protein phosphatases as negative regulators of kinase activation

被引:125
作者
Sugiyama, K
Sugiura, K
Hara, T
Sugimoto, K
Shima, H
Honda, K
Furukawa, K
Yamashita, S
Urano, T
机构
[1] Nagoya Univ, Sch Med, Dept Biochem 2, Showa Ku, Nagoya, Aichi 4660065, Japan
[2] Nagasaki Univ, Sch Med, Dept Nat Med, Atom Bomb Dis Inst, Nagasaki 8528523, Japan
[3] Osaka Prefecture Univ, Div Appl Biochem, Grad Sch Agr & Biol Sci, Sakai, Osaka 5998531, Japan
[4] Hokkaido Univ, Div Biochem Oncol & Immunol, Inst Med Genet, Kita Ku, Sapporo, Hokkaido 0600815, Japan
关键词
Aurora-B; historic H3; protein phosphatase; okadaic acid; substrate specificity;
D O I
10.1038/sj.onc.1205432
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human serine/threonine kinase Aurora-B is structurally related to the protein kinase Ip11p 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 I (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.
引用
收藏
页码:3103 / 3111
页数:9
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