14-3-3 gamma is stimulated by IL-3 and promotes cell proliferation.
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 14-3-3gamma was significantly increased by IL-3 stimulation at both the transcriptional and translational levels. 14-3-3gamma 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 14-3-3gamma 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 14-3-3gamma, resulting in cell death. These results indicate that deregulated expression of 14-3-3gamma may contribute to malignant transformation, possibly providing a new target for therapeutic intervention in hematopoietic neoplasms.
Ajjappala
Brijesh S
BS
Graduate School of Life Science and Biotechnology, Cell and Gene Therapy Research Institute, Pochon CHA University, CHA General Hospital, Seoul, Korea.
Kim
Yong-Soo
YS
Kim
Myung-Sun
MS
Lee
Min-Young
MY
Lee
Kwang-Youl
KY
Ki
Ho-Yun
HY
Cha
Dong-Hyun
DH
Baek
Kwang-Hyun
KH
D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D020014:K562 Cells; D007939:Leukemia L1210 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D048948:14-3-3 Proteins; D007377:Interleukin-3; D020033:Protein Isoforms