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

Cytoplasmic protein tyrosine kinases play crucial roles in signaling, ia 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 mo nocytic lineages. Here we show that Bmx is catalytically activated by inter leukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) receptors , Activation of Ems required phosphatidylinositol 3-kinase (PI-3K) as demon strated by the ability of PI-3K inhibitors to block the activation signal. A green fluorescent protein (GFP) tagged Bmx nas translocated to cellular m embranes upon co-expression of a constitutively active form of PI-3K, furth er indicating a role for PI-3K in signaling upstream of Ems. 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 d ifferentiated into mature granulocytes. However, Bmx did not modulate IL-3- dependent proliferation of the cells. These results demonstrate distinct ef fects of Ems in cytokine induced proliferation and differentiation of myelo id cells, and suggest that the stage specific expression of Ems is critical for the differentiation of myeloid cells.