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Constitutive phosphorylation of a Rac GAP MgcRacGAP is implicated in v-Src-induced transformation of NIH3T3 cells

  1. Noriko Doki1,2,
  2. Toshiyuki Kawashima1,*,
  3. Yasushi Nomura1,
  4. Akiho Tsuchiya1,
  5. Chitose Oneyama3,
  6. Tsuyoshi Akagi4,
  7. Yoshihisa Nojima2,
  8. Toshio Kitamura1,*

Article first published online: 31 MAY 2009

DOI: 10.1111/j.1349-7006.2009.01235.x

Issue

Cancer Science

Cancer Science

Volume 100, Issue 9, pages 1675–1679, September 2009

Additional Information

How to Cite

Doki, N., Kawashima, T., Nomura, Y., Tsuchiya, A., Oneyama, C., Akagi, T., Nojima, Y. and Kitamura, T. (2009), Constitutive phosphorylation of a Rac GAP MgcRacGAP is implicated in v-Src-induced transformation of NIH3T3 cells. Cancer Science, 100: 1675–1679. doi: 10.1111/j.1349-7006.2009.01235.x

Author Information

  1. 1

    Division of Cellular Therapy, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo

  2. 2

    Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gumma

  3. 3

    Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka

  4. 4

    KAN Research Institute, Inc. Kobe MI R&D Center, Chuo-ku, Kobe, Japan

* To whom correspondence should be addressed. E-mail: kkawa@ims.u-tokyo.ac.jp and kitamura@ims.u-tokyo.ac.jp

Publication History

  1. Issue published online: 11 AUG 2009
  2. Article first published online: 31 MAY 2009
  3. (Received April 9, 2009/Revised May 16, 2009/Accepted May 20, 2009)

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MgcRacGAP plays critical roles in cell division through regulating Rho family small GTPases. As we previously reported, phosphorylation of MgcRacGAP on serine 387 (S387) is induced by Aurora B kinase at the midbody during cytokinesis, which is a critical step of cytokinesis. Phosphorylation of S387-MgcRacGAP converts it from RacGAP to RhoGAP, leading to completion of cytokinesis. Here we show that MgcRacGAP is prominently phosphorylated on S387 even in the interphase of v-Src-transformed NIH3T3 cells in the cytoplasm, but not in the interphase of parental NIH3T3 or H-RasV12-transformed NIH3T3 cells. Interestingly, levels of phosphorylation on S387 (pS387) correlated with soft agar colony-forming abilities of v-Src-transformed NIH3T3 cells. Expression of a phosphorylation-mimic mutant MgcRacGAP-S387D enhanced colony formation of v-Src-transformed NIH3T3 cells. Surprisingly, a Rac1 inhibitor but not kinase inhibitors including Aurora B kinase inhibitor specifically inhibited phosphorylation of S387-MgcRacGAP in v-Src-transformed NIH3T3 cells, suggesting the v-Src-induced pathological positive feedback mechanisms towards Rac1 activation using pS387-MgcRacGAP. These results indicated the difference in the mechanisms between v-Src- and H-RasV12-induced transformation, and should shed some light on pathological roles of disordered phosphorylation of MgcRacGAP at S387 in v-Src-induced cell transformation. (Cancer Sci 2009; 100: 1675–1679)

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