| Popis: |
The receptor for erythropoietin is restricted to cells of mature erythroid and possibly megakaryocyte lineages. Studies in cell lines have suggested that cytokine receptors share a conserved signaling pathway for proliferation. We retrovirally transduced the erythropoietin receptor or a constitutively activated form of the EPOR into normal hematopoietic progenitors, including blast cell colonies. The EPO-R was able to support the proliferation and differentiation of early erythroid, early megakaryocytic, and macrophage progenitors, but not granulocyte progenitors. Blast cell colonies transduced with the EPO-R proliferate in response to EPO but the development of erythroid cells was not favored over other lineages. These results with normal cells suggest that some but not all cytokine receptors exhibit shared signaling pathways, and that EPO signaling alone is not sufficient to drive erythroid development. The Janus family of cytosolic tyrosine kinases mediate cytokine initiated mitogenic signals. We have determined that the EPO-R box 1 cytoplasmic motif is required for the binding and activation of JAK2. However, sequences outside the box 1 domain most likely regulate the specificity of JAK kinase association. |
