TY - JOUR
T1 - Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis
AU - Minoshima, Yukinori
AU - Kawashima, Toshiyuki
AU - Hirose, Koichi
AU - Tonozuka, Yukio
AU - Kawajiri, Aie
AU - Bao, Ying Chun
AU - Deng, Xingming
AU - Tatsuka, Masaaki
AU - Narumiya, Shuh
AU - May, W. Stratford
AU - Nosaka, Tetsuya
AU - Semba, Kentaro
AU - Inoue, Takafumi
AU - Satoh, Takaya
AU - Inagaki, Masaki
AU - Kitamura, Toshio
N1 - Funding Information:
We thank Dr. Y. Kaziro for critical reading of the manuscript, Dr. S. Imajoh-Ohmi for valuable discussions, and M. Ohara for language assistance. The Division of Hematopoietic factors is supported by the Chugai Pharmaceutical Company. This work was also supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by the Ministry of Health, Labor, and Welfare of Japan, and by a grant from the NAKAJIMA foundation.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1534-5807(03)00089-3
DO - 10.1016/S1534-5807(03)00089-3
M3 - Article
C2 - 12689593
AN - SCOPUS:0037387766
SN - 1534-5807
VL - 4
SP - 549
EP - 560
JO - Developmental Cell
JF - Developmental Cell
IS - 4
ER -