FEBS Letters
Volume 582, Issue 8 , Pages 1182-1188, 9 April 2008

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

Edited by Angel Nebreda

  • Aminata Touré

      Affiliations

    • Institut Cochin, Département de Génétique et Développement, INSERM U567/CNRS UMR8104/Université Paris Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    • These authors contributed equally to this work.
  • ,
  • Rym Mzali

      Affiliations

    • INSERM U749, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France
    • These authors contributed equally to this work.
  • ,
  • Caroline Liot

      Affiliations

    • INSERM U749, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France
  • ,
  • Laetitia Seguin

      Affiliations

    • INSERM U749, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France
  • ,
  • Laurence Morin

      Affiliations

    • Institut Cochin, Département de Génétique et Développement, INSERM U567/CNRS UMR8104/Université Paris Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
  • ,
  • Catherine Crouin

      Affiliations

    • INSERM U749, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France
  • ,
  • Ilin Chen-Yang

      Affiliations

    • Institute of Biochemistry and Molecular Biology and Proteomics Research Center, National Yang-Ming University, 155 Li-Nong Street Section 2, Taipei, Taiwan
  • ,
  • Yeou-Guang Tsay

      Affiliations

    • Institute of Biochemistry and Molecular Biology and Proteomics Research Center, National Yang-Ming University, 155 Li-Nong Street Section 2, Taipei, Taiwan
  • ,
  • Olivier Dorseuil

      Affiliations

    • Institut Cochin, Département de Génétique et Développement, INSERM U567/CNRS UMR8104/Université Paris Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
  • ,
  • Gérard Gacon

      Affiliations

    • Institut Cochin, Département de Génétique et Développement, INSERM U567/CNRS UMR8104/Université Paris Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    • Corresponding Author InformationCorresponding authors.
  • ,
  • Jacques Bertoglio

      Affiliations

    • INSERM U749, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément 92296 Châtenay-Malabry, France
    • Corresponding Author InformationCorresponding authors.

Received 17 July 2007; received in revised form 29 November 2007; accepted 7 December 2007. published online 15 January 2008.

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 B56ε, 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.

Structured summary:

MINT-6166761:

Aurora B (uniprotkb:Q96GD4) phosphorylates (MI:0217) MgcRacGAP (uniprotkb:Q9H0H5) by protein kinase assay (MI:0424)

MINT-6166774:

Cdk1 (uniprotkb:P06493) phosphorylates (MI:0217) MgcRacGAP (uniprotkb:Q9H0H5) by protein kinase assay (MI:0424)

MINT-6166653:

PP2A (uniprotkb:P67775) dephosphorylates (MI:0203) MgcRacGAP (uniprotkb:Q9H0H5) by phosphatase assay (MI:0434)

MINT-6166710, MINT-6166727, MINT-6166735:

MgcRacGAP (uniprotkb:Q9H0H5)physically interacts (MI:0218) with B56ε (uniprotkb:Q16537) by coimmunoprecipitation (MI:0019)

MINT-6166691:

B56ε (uniprotkb:Q16537) physically interacts (MI:0218) with MgcRacGAP (uniprotkb:Q9H0H5) by far western blotting (MI:0047)

MINT-6166556:

MgcRacGAP (uniprotkb:Q9H0H5) physically interacts (MI:0218) with B56ε (uniprotkb:Q16537) by two-hybrid (MI:0018)

MINT-6166634:

MgcRacGAP (uniprotkb:Q9H0H5) physically interacts (MI:0218) with Ect2 (uniprotkb:Q9H8V3) by coimmunoprecipitation (MI:0019)

MINT-6166596:

MKLP-1 (uniprotkb:Q02241) physically interacts (MI:0218) with B56ε (uniprotkb:Q16537) , MgcRacGAP (uniprotkb:Q9H0H5), PP2A (uniprotkb:P67775) bycoimmunoprecipitation (MI:0019)

Keywords: RhoGAP, Phosphorylation, Phosphoprotein Phosphatase 2A, Cytokinesis

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PII: S0014-5793(08)00012-4

doi:10.1016/j.febslet.2007.12.036

Refers to corrigendum:

  • Corrigendum to “Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase” [FEBS Lett. 582 (2008) 1182–1188] , 14 April 2008

    Aminata Touré, Rym Mzali, Caroline Liot, Laetitia Seguin, Laurence Morin, Catherine Crouin, Ilin Chen-Yang, Yeou-Guang Tsay, Olivier Dorseuil, Gérard Gacon, Jacques Bertoglio
    FEBS Letters 14 May 2008 (Vol. 582, Issue 11, Page 1635)

FEBS Letters
Volume 582, Issue 8 , Pages 1182-1188, 9 April 2008