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Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A

Kang Zeng1, Ricardo Nunes Bastos, Francis A Barr

  • 1University of Liverpool, Cancer Research Centre, Liverpool L3 9TA, England, UK.

The Journal of Cell Biology
|December 29, 2010
PubMed

Insights

Protein Phosphatase 6 (PP6) is identified as the key T-loop phosphatase for Aurora A kinase. Loss of PP6 impairs cell division by increasing Aurora A activity, highlighting PP6

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein kinases are crucial regulators of cellular processes, often activated by T-loop phosphorylation.
  • Specific T-loop phosphatases that reverse kinase activation are less understood than kinase activators.
  • Aurora A is an essential mitotic kinase involved in spindle formation and chromosome alignment.

Purpose of the Study:

  • To identify the T-loop phosphatase responsible for regulating Aurora A kinase activity.
  • To investigate the role of this phosphatase in mitotic progression and spindle assembly.
  • To elucidate the mechanism by which this phosphatase controls Aurora A function.

Main Methods:

  • Depletion of protein phosphatase 6 (PP6) subunits in human cells.
  • Analysis of Aurora A T-loop phosphorylation levels and activity.
  • Assessment of spindle formation and chromosome alignment.
  • In vitro phosphatase assays using purified PP6 and Aurora A-TPX2 complexes.

Main Results:

  • PP6 holoenzyme identified as the primary T-loop phosphatase for Aurora A.
  • PP6 depletion leads to increased Aurora A activity, affecting spindle formation and chromosome alignment.
  • Purified PP6 dephosphorylates Aurora A T-loop in vitro, while inactive mutants do not.
  • PP6 depletion specifically increases Aurora A T-loop phosphorylation and Aurora A-TPX2 complex stability.

Conclusions:

  • PP6 plays a critical, previously unappreciated role as the T-loop phosphatase regulating Aurora A activity.
  • Dysregulation of PP6-mediated Aurora A dephosphorylation disrupts essential mitotic events.
  • This study highlights the general importance of T-loop phosphatases in controlling kinase activity and cell division.

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