Tpo-stimulated c-Mpl is degraded by both the proteasome and the lysosome. (A) BaF-Mpl cells were treated with Chx for 0 to 240 minutes to inhibit synthesis of new protein in conjunction with or without rhTpo, MG-132, and NH4Cl. c-Mpl degradation was determined by the presence or absence of the mature 85-kDa form of c-Mpl. (B) Similar experiments were also performed on bone marrow–derived murine megakaryocytes and human platelets. The data shown are representative of 3 independent experiments.