Neither EPO-induced activation of JAK2 tyrosine kinase nor tyrosine phosphorylation of the EPO-R was required for EPO internalization and receptor downregulation. ¹²⁵I-EPO internalization studies. Solid lines represent the percentage of total bound counts at time 0 that were internalized. Broken lines represent 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, thus, are not shown. Internalization studies were performed at least 3 times for each clone. Data presented are from a single representative clone of each. (□) Wild-type EPO-R(1-483); (▪) EPO-R(W282R); and (○) EPO-R(YF).