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Proto-Oncogene Products Vav and c-Cbl are Involved in the Signal Transduction Through Grb2/Ash in Hematopoietic Cells

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Molecular Biology of Hematopoiesis 5

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Summary

Grb2/Ash is composed of one SH2 and two SH3 domains and functions as an adapter linking tyrosine-kinase receptors and Ras in fibroblasts. We have investigated the nature of proteins interacting with Grb2/Ash in hematopoietic cells.

The product of the vav proto-oncogene (Vav) is exclusively expressed in hematopoietic cells and has the guanine nucleotide exchange activity. Here we report that granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and erythropoietin (EPO) induce rapid and transient tyrosine phosphorylation of Vav and that Vav is constitutively associated with the SH3 domain of Grb2/Ash in a human leukemia cell line UT-7. These data suggest that Vav is implicated in a signaling pathway leading to activation of Ras or Ras-related proteins in hematopoietic cells.

Furthermore, we have shown that the proto-oncogene c-cblc product (c-Cbl) is also tyrosine-phosphorylated by stimulation with GM-CSF or EPO and is constitutively associated with the SH3 domain of Grb2/Ash in UT-7. However, we could not find the homologous regions with guanine nucleotide exchange factors or GTPase-activating proteins in the c-cbl gene. Therefore, Grb2/Ash might also transduce a signal that is different from the signal leading to the small-G protein regulation.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113, Japan

    Yutaka Hanazono, Hideharu Odai, Ko Sasaki, Yoshio Yazaki & Hisamaru Hirai M.D. Ph.D.

  2. Kirin Brewery Co. Ltd, Central Laboratory for Key Technology, Fukuura 1-13-5, Kanazawa-ku, Yokohama, Kanagawa, 236, Japan

    Akihiro Iwamatsu

  3. Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113, Japan

    Hisamaru Hirai M.D. Ph.D.

Authors
  1. Yutaka Hanazono
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  2. Hideharu Odai
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  3. Ko Sasaki
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  4. Akihiro Iwamatsu
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  5. Yoshio Yazaki
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  6. Hisamaru Hirai M.D. Ph.D.
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Editor information

Editors and Affiliations

  1. The Rockefeller University, New York, New York, USA

    Nader G. Abraham

  2. University of Tokyo, Tokyo, Japan

    Shigetaka Asano

  3. Universität-Gesamthoschschule Essen, Essen, Germany

    Günther Brittinger

  4. Istituto Cantonale di Patologia, Locarno, Switzerland

    Georges J. M. Maestroni

  5. Western Pennsylvania Cancer Institute, Pittsburgh, Pennsylvania, USA

    Richard K. Shadduck

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© 1996 Plenum Press, New York

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Hanazono, Y., Odai, H., Sasaki, K., Iwamatsu, A., Yazaki, Y., Hirai, H. (1996). Proto-Oncogene Products Vav and c-Cbl are Involved in the Signal Transduction Through Grb2/Ash in Hematopoietic Cells. In: Abraham, N.G., Asano, S., Brittinger, G., Maestroni, G.J.M., Shadduck, R.K. (eds) Molecular Biology of Hematopoiesis 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0391-6_47

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  • DOI: https://doi.org/10.1007/978-1-4613-0391-6_47

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-8031-3

  • Online ISBN: 978-1-4613-0391-6

  • eBook Packages: Springer Book Archive

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