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14-3-3 Is Stimulated by IL-3 and Promotes Cell Proliferation¹

Brijesh S. Ajjappala^*, Yong-Soo Kim^*, Myung-Sun Kim^*, Min-Young Lee^*, Kwang-Youl Lee, Ho-Yun Ki^*, Dong-Hyun Cha and Kwang-Hyun Baek^2,*

^* Graduate School of Life Science and Biotechnology, Cell and Gene Therapy Research Institute, Pochon CHA University, CHA General Hospital, Seoul, Korea; College of Pharmacy, Chonnam National University, Buk-Gu, Gwangju, Korea; and Division of Gynecology and Obstetrics, CHA General Hospital, Pochon CHA University, Seoul, Korea

IL-3 plays important roles in the growth and survival of hematopoietic progenitor cells, processes modeled in studies of the IL-3-dependent cell line Ba/F3. To gain insights into molecular mechanisms governing cell fate, we examined the patterns of proteins up-regulated following stimulation of Ba/F3 cells with IL-3. Through two-dimensional electrophoresis and proteomics-based approaches, we identified 11 proteins. Of these, expression of 14-3-3 was significantly increased by IL-3 stimulation at both the transcriptional and translational levels. 14-3-3 overexpression in Ba/F3 cells abrogated dependence on IL-3 and was associated with activation of PI3K and MAPK signaling cascades, suggesting that the functions of 14-3-3 in normal hematopoietic progenitors are to promote survival and growth through the activation of distinct signaling pathways. Additionally, the up-regulation of Bax and Bad was seen with the ablation of 14-3-3, resulting in cell death. These results indicate that deregulated expression of 14-3-3 may contribute to malignant transformation, possibly providing a new target for therapeutic intervention in hematopoietic neoplasms.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the grants of the Korea Health 21 Research and Development Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea (01-PJ10-PG6-01GN13-0002 and the Biomedical Proteome Research Center (A030003)).

² Address correspondence and reprint requests to Dr. Kwang-Hyun Baek, Cell and Gene Therapy Research Institute, Pochon CHA University, CHA General Hospital, 606-16 Yeoksam 1-Dong, Kangnam-Gu, Seoul 135-081, Korea. E-mail address: baek{at}cha.ac.kr

³ Abbreviations used in this paper: 2-DE, two-dimensional electrophoresis; LC-MS/MS, liquid chromatography-mass spectroscopy/mass spectroscopy.

⁴ The online version of this article contains supplemental material.