A membrane-proximal 69 amino acid domain of the EPO-R cytoplasmic tail is the minimal domain required for internalization of EPO and receptor downregulation. ¹²⁵I-EPO internalization studies. (A) The percentage of total bound counts at time 0 that were internalized. (B) The percentage of total bound counts at time 0 that remained surface bound. Standard deviations for each point were within 10% of the value plotted and are not shown. At each time point, the summation of internalized EPO, surface-bound EPO, and counts in the medium equaled the amount of ¹²⁵I-EPO bound at time 0. Internalization studies were performed on 2 clones for each EPO-R isoform and were performed 2 times for each clone. Data presented are from a single representative clone of each. (□) Wild-type EPO-R(1-483); (▪) EPO-R(1-411); (▵) EPO-R(1-373); (○) EPO-R(1-321); and (•) EPO-R(1-252).