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

Oncogene. 2002 May 9;21(20):3103-11. doi: 10.1038/sj.onc.1205432.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / chemistry
  • Aurora Kinase B
  • Aurora Kinases
  • COS Cells
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Nuclear Proteins / physiology
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / physiology*
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational / physiology*
  • Protein Serine-Threonine Kinases / physiology*
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity

Substances

  • Histones
  • Isoenzymes
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Phosphoserine
  • Okadaic Acid
  • Arginine
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • Phosphoprotein Phosphatases
  • protein phosphatase 5