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

• Published in: FEBS letters Vol. 582; no. 8; pp. 1182 - 1188
• Main Authors: Touré, Aminata, Mzali, Rym, Liot, Caroline, Seguin, Laetitia, Morin, Laurence, Crouin, Catherine, Chen-Yang, Ilin, Tsay, Yeou-Guang, Dorseuil, Olivier, Gacon, Gérard, Bertoglio, Jacques
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 09.04.2008
• Subjects: Animals; Aurora Kinase B; Aurora Kinases; CDC2 Protein Kinase - metabolism; Cell Line, Tumor; Cercopithecus aethiops; Chromatography, High Pressure Liquid; COS Cells; Cytokinesis; GTPase-Activating Proteins - physiology; Humans; Mitosis - physiology; Phosphoprotein Phosphatase 2A; Phosphorylation; Protein Phosphatase 2 - metabolism; Protein-Serine-Threonine Kinases - metabolism; RhoGAP; Tandem Mass Spectrometry; Two-Hybrid System Techniques; Phosphoprotein Phosphatase 2A; Phosphorylation; Cytokinesis; RhoGAP
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.12.036

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)