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


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.


Tyrosine Phosphorylation Guanine Nucleotide Exchange Factor Normal Rabbit Serum Lx107 Cell Kirin Brewery 
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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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