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The Bmx tyrosine kinase is activated by IL-3 and G-CSF in a PI-3K dependent manner

Oncogene volume 19, pages 4151–4158 (2000)Cite this article

Abstract

Cytoplasmic protein tyrosine kinases play crucial roles in signaling via a variety of cell surface receptors. The Bmx tyrosine kinase, a member of the Tec family, is expressed in hematopoietic cells of the granulocytic and monocytic lineages. Here we show that Bmx is catalytically activated by interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) receptors. Activation of Bmx required phosphatidylinositol 3-kinase (PI-3K) as demonstrated by the ability of PI-3K inhibitors to block the activation signal. A green fluorescent protein (GFP) tagged Bmx was translocated to cellular membranes upon co-expression of a constitutively active form of PI-3K, further indicating a role for PI-3K in signaling upstream of Bmx. The expression of wild type Bmx in 32D myeloid progenitor cells resulted in apoptosis in the presence of G-CSF, while cells expressing a kinase dead mutant of Bmx differentiated into mature granulocytes. However, Bmx did not modulate IL-3-dependent proliferation of the cells. These results demonstrate distinct effects of Bmx in cytokine induced proliferation and differentiation of myeloid cells, and suggest that the stage specific expression of Bmx is critical for the differentiation of myeloid cells.

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Acknowledgements

We are grateful to Drs Riitta Alitalo, Julian Downward, Shigekazu Nagata and Petri Salven for kindly providing the reagents specified in the Materials and methods and to Mari Helanterä and Tapio Tainola for the excellent technical assistance. This work was supported by the Finnish Cancer Organization, the Finnish Academy, the Sigrid Juselius Foundation, the University of Helsinki and the European Union BioThechnology program (BIO4-CT98-0142). In addition, N Ekman was supported by grants from Helsinki University Biomedical Graduate School, Medicinska Understödsföreningen Liv och Hälsa and from the Blood Disease Research Foundation.

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  1. Niklas Ekman and Elena Arighi: N Ekman and E Arighi contributed equally to this work

Authors and Affiliations

  1. Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, P.O.Box 21 (Haartmaninkatu 3), 00014 University of Helsinki, Finland

    Niklas Ekman, Elena Arighi, Iiro Rajantie & Kari Alitalo

  2. Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, 20133, Italy

    Elena Arighi

  3. Department of Virology, Haartman Institute, P.O.Box 21 (Haartmaninkatu 3), 00014 University of Helsinki, Finland

    Pipsa Saharinen & Olli Silvennoinen

  4. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 140, 00029, Helsinki, Finland

    Ari Ristimäki

  5. Medical Biochemistry, University of Tampere, Tampere, 33014, Finland

    Olli Silvennoinen

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Ekman, N., Arighi, E., Rajantie, I. et al. The Bmx tyrosine kinase is activated by IL-3 and G-CSF in a PI-3K dependent manner. Oncogene 19, 4151–4158 (2000). https://doi.org/10.1038/sj.onc.1203763

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