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

  • Yutaka Hanazono
  • Hideharu Odai
  • Ko Sasaki
  • Akihiro Iwamatsu
  • Yoshio Yazaki
  • Hisamaru Hirai

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.

Keywords

Tyrosine Phosphorylation Guanine Nucleotide Exchange Factor Normal Rabbit Serum Lx107 Cell Kirin Brewery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Yutaka Hanazono
    • 1
  • Hideharu Odai
    • 1
  • Ko Sasaki
    • 1
  • Akihiro Iwamatsu
    • 2
  • Yoshio Yazaki
    • 1
  • Hisamaru Hirai
    • 1
    • 3
  1. 1.Third Department of Internal Medicine, Faculty of MedicineUniversity of TokyoBunkyo-ku, TokyoJapan
  2. 2.Kirin Brewery Co. LtdCentral Laboratory for Key TechnologyKanagawaJapan
  3. 3.Third Department of Internal Medicine, Faculty of MedicineUniversity of TokyoBunkyo-ku, TokyoJapan

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