Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase

FEBS Lett. 2008 Apr 9;582(8):1182-8. doi: 10.1016/j.febslet.2007.12.036. Epub 2008 Jan 15.

Abstract

MgcRacGAP, a Rho GAP essential to cytokinesis, works both as a Rho GTPase regulator and as a scaffolding protein. MgcRacGAP interacts with MKLP1 to form the centralspindlin complex and associates with the RhoGEF Ect2. The GAP activity of MgcRacGAP is regulated by Aurora B phosphorylation. We have isolated B56epsilon, a PP2A regulatory subunit, as a new MgcRacGAP partner. We report here that (i) MgcRacGAP is phosphorylated by Aurora B and Cdk1, (ii) PP2A dephosphorylates Aurora B and Cdk1 phosphorylated sites and (iii) inhibition of PP2A abrogates MgcRacGAP/Ect2 interaction. Therefore, PP2A may regulate cytokinesis by dephosphorylating MgcRacGAP and its interacting partners.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • CDC2 Protein Kinase / metabolism*
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Chromatography, High Pressure Liquid
  • GTPase-Activating Proteins / physiology*
  • Humans
  • Mitosis / physiology*
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Tandem Mass Spectrometry
  • Two-Hybrid System Techniques

Substances

  • GTPase-Activating Proteins
  • mgcRacGAP
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • PPP2CA protein, human
  • Protein Phosphatase 2