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Anti-apoptotic function of Rac in hematopoietic cells

Oncogene volume 18, pages 407–415 (1999)Cite this article

Abstract

The small GTP-binding protein Rac plays a pivotal role in the regulation of diverse physiological events including reorganization of the actin cytoskeleton, cell cycle progression, and transformation. Here we show an anti-apoptotic effect of Rac in interleukin-3-dependent murine hematopoietic BaF3 cells. Activated Rac(G12V), when ectopically expressed in BaF3 cells, rendered the cells resistant to apoptosis upon interleukin-3 deprivation, while activated mutants of Rho and Cdc42 displayed no significant anti-apoptotic effect. In contrast to activated Ras, which also supports cell survival in the absence of interleukin-3, Rac required fetal bovine serum for the prevention of cell death. The involvement of phosphatidylinositol 3-kinase downstream of Rac was demonstrated by the inhibition of Rac-induced cell survival by wortmannin and LY294002 and the presence of phosphatidylinositol kinase activity in the Rac immunoprecipitate. Furthermore, the serine/threonine kinase Akt was stimulated by activated Rac and fetal bovine serum in a synergistic manner. Rac-induced Akt activation was mediated by phosphorylation of threonine-308 and serine-473. In addition to the phosphatidyl-inositol 3-kinase/Akt pathway, the p38 mitogen-activated protein kinase pathway was crucial for Rac-dependent survival, whereas p38 mitogen-activated protein kinase was not implicated in Ras-induced anti-apoptotic signaling. These findings provide evidence for the involvement of Rac in survival signaling of hematopoietic cells.

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Acknowledgements

We are grateful to Kozo Kaibuchi, Richard A Cerione, Ushio Kikkawa for materials. We also thank Motoshi Nagao, Jotaro Suzuki, Junji Yamauchi and Yuji Yamazaki for assistance. This work was supported in part by CREST of the Japan Science and Technology Corporation. Our laboratory at Tokyo Institute of Technology is supported by Shering-Plough Corporation.

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  1. Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan

    Takaya Satoh

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  1. Kazuhiko Nishida
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Nishida, K., Kaziro, Y. & Satoh, T. Anti-apoptotic function of Rac in hematopoietic cells. Oncogene 18, 407–415 (1999). https://doi.org/10.1038/sj.onc.1202301

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