TYROSINE PHOSPHORYLATION OF THE PROTOONCOGENE PRODUCT VAV AND ITS ASSOCIATION WITH THE ADAPTER GRB2 ASH IN A HUMAN LEUKEMIA-CELL LINE UT-7/

The vav proto-oncogene product (Vav) is expressed exclusively in hemat opoietic cells and is reported to have guanine nucleotide exchange act ivity. Here we report that granulocyte-macrophage colony-stimulating f actor, interleukin-3, and erythropoietin induce tyrosine phosphorylati on of Vav in a human leukemia cell line UT-7. Tyrosine phosphorylation of Vav is rapid and transient; it occurs within 1 min of the stimulat ion and at physiological concentrations of the factors. Furthermore, w e show that Vav is constitutively associated with the adapter molecule Grb2/Ash in UT-7. These data suggest that tryosine kinases, the adapt er Grb2/Ash, and the guanine nucleotide exchange factor Vav are member s of a signaling pathway leading to Ras activation in hematopoietic ce lls.