Receptors that induce erythroid differentiation of Ba/F3 cells: structural requirements and effect on STAT5 binding.

摘要: Ectopic expression of the erythropoietin receptor (EpoR) in interleukin-3 (IL-3)–dependent cell line Ba/F3 results growth and partial erythroid differentiation Epo. In contrast, introduction activation interleukin-5 (IL-5R) or granulocyte-macrophage colony-stimulating factor (GM-CSFR) proliferation only. As this effect is specific to EpoR, role its extracellular cytoplasmic domain was tested after construction two chimeric receptors. One contained EpoR fused endodomain IL-3R β-chain (E/β), while other region GM-CSFR α-chain (GMER). Surprisingly, both receptors induced ruling out a strict specificity process. Instead ability signal correlated with structural features shared by GMER, E/β Dimerization all three pairing transducing chains cytoplasm, contrast mitogenic IL-3R, IL-5R, GM-CSFR, which assemble as αβ heterodimers. Two new that fulfilled requirement exemplified but lacked any part were designed consolidate model. They consisted ectodomains GMR-α IL-5Rα, respectively, β-chain. Both effective signaling response their cognate ligand. Another property fulfilling these requirements they cause marked delay transducers activators transcription 5 (STAT5) on ligand stimulation. Taken together our studies show assembly dictates potential cells, can take place absence Epo STAT5 highly predictive