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TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways

Leukemia volume 18, pages 548–555 (2004)Cite this article

Abstract

We previously reported the fusion of the TEL gene to the Syk gene in myelodysplastic syndrome with t(9;12)(q22;p12). TEL-Syk fusion transformed interleukin-3 (IL-3)-dependent murine hematopoietic cell line BaF3 to growth factor independence. Here, we investigate the intracellular signal transduction of the stable transfectants. TEL-Syk fusion protein was associated with the p85 subunit of phosphatidyl inositol 3 kinase (PI3-K) followed by the activation of Akt in the absence of IL-3. Vav, phospholipase C-γ2 and mitogen-activated protein kinase (MAPK) were also constitutively activated. TEL-Syk also activated the signal transducer and activator of transcription 5 (STAT5) in the absence of Janus kinase 2 activation. None of these kinases were phosphorylated in the BaF3 cells transfected with TELΔPNT-Syk in which the oligomerization domain of TEL was deleted. Inhibitor analysis showed that the MAPK pathway was important in TEL-Syk-mediated cell proliferation. The immunofluorescence technique revealed that the TEL-Syk fusion protein was located in the cytoplasm. These data suggest that TEL-Syk fusion protein in the cytoplasm leads to the constitutive activation of PI3-K/Akt, MAPK and STAT5 signal pathways, which are closely involved in IL-3-independent cell proliferation of BaF3 cells.

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Acknowledgements

We thank Dr JN Ihle for providing anti-STAT5 antisera, Dr Kazuhito Yamamoto and Hitoshi Kiyoi for helpful discussions, and Satoshi Suzuki and Chika Wakamatsu for their excellent technical assistance. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Osaka Foundation for Promotion of Clinical Immunology, the Akiyama Foundation, the Suhara Memorial Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research and the Uehara Memorial Foundation.

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Authors and Affiliations

  1. Department of Hematology, Graduate School of Medicine, Nagoya University, Nagoya, Japan

    T Kanie, A Abe, M Towatari, N Emi & T Naoe

  2. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    T Matsuda & T Yamamoto

  3. Department of Hematological Oncology, Gifu Prefectural Tajimi Hospital, Tajimi, Japan

    Y Kuno

  4. Nagoya National Hospital, Nagoya, Japan

    H Saito

  5. Aichi Blood Disease Research Foundation, Nagoya, Japan

    H Saito

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Correspondence to A Abe.

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Kanie, T., Abe, A., Matsuda, T. et al. TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways. Leukemia 18, 548–555 (2004). https://doi.org/10.1038/sj.leu.2403266

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