Multiple Signals Mediate Proliferation, Differentiation, and Survival from the Granulocyte Colony-stimulating

Granulocyte colony-stimulating factor (G-CSF) regu-lates neutrophil production through activation of its cognate receptor, the G-CSF-R. Previous studies with deletion mutants have shown that the membrane-prox-imal cytoplasmic domain of the receptor is sufficient for mitogenic signaling, whereas the membrane-distal do-main is required for differentiation signaling. However, the function of the four cytoplasmic tyrosines of the G-CSF-R in the control of proliferation, differentiation, and survival has remained unclear. Here we investi-gated the role of these tyrosines by expressing a tyrosine “null ” mutant and single tyrosine “add back ” mutants in maturation-competent myeloid 32D cells. Clones ex-pressing the null mutant showed only minimal prolifer-ation and differentiation, with survival also reduced a