Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis.
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.
Minoshima
Yukinori
Y
Division of Hematopoietic Factors, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Kawashima
Toshiyuki
T
Hirose
Koichi
K
Tonozuka
Yukio
Y
Kawajiri
Aie
A
Bao
Ying Chun
YC
Deng
Xingming
X
Tatsuka
Masaaki
M
Narumiya
Shuh
S
May
W Stratford
WS
Nosaka
Tetsuya
T
Semba
Kentaro
K
Inoue
Takafumi
T
Satoh
Takaya
T
Inagaki
Masaki
M
Kitamura
Toshio
T
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
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