title: Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis.
abstract: Cell division is finely controlled by various molecules including small G proteins and kinases/phosphatases. Among these, Aurora B, RhoA, and the GAP MgcRacGAP have been implicated in cytokinesis, but their underlying mechanisms of action have remained unclear. Here, we show that MgcRacGAP colocalizes with Aurora B and RhoA, but not Rac1/Cdc42, at the midbody. We also report that Aurora B phosphorylates MgcRacGAP on serine residues and that this modification induces latent GAP activity toward RhoA in vitro. Expression of a kinase-defective mutant of Aurora B disrupts cytokinesis and inhibits phosphorylation of MgcRacGAP at Ser387, but not its localization to the midbody. Overexpression of a phosphorylation-deficient MgcRacGAP-S387A mutant, but not phosphorylation-mimic MgcRacGAP-S387D mutant, arrests cytokinesis at a late stage and induces polyploidy. Together, these findings indicate that during cytokinesis, MgcRacGAP, previously known as a GAP for Rac/Cdc42, is functionally converted to a RhoGAP through phosphorylation by Aurora B.
authors.affiliation: Division of Hematopoietic Factors, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Minoshima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kawashima
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tonozuka
authors.forename: Aie
authors.initials: A
authors.lastname: Kawajiri
authors.forename: Ying Chun
authors.initials: YC
authors.lastname: Bao
authors.forename: Xingming
authors.initials: X
authors.lastname: Deng
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tatsuka
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: W Stratford
authors.initials: WS
authors.lastname: May
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Takaya
authors.initials: T
authors.lastname: Satoh
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002455:Cell Division / Q000235:genetics*; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000201:enzymology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008938:Mitosis / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D012694:Serine / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D020690:GTPase-Activating Proteins; C115995:mgcRacGAP; C085379:rho GTPase-activating protein; D012694:Serine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D020742:rhoA GTP-Binding Protein