title: Exposure of K562 cells to anti-receptor monoclonal antibody OKT9 results in rapid redistribution and enhanced degradation of the transferrin receptor.
abstract: When the human erythroleukemia cell line K562 is treated with OKT9, a monoclonal antibody against the transferrin receptor, effects on receptor dynamics and degradation ensue. The apparent half-life of the receptor is decreased by greater than 50% as a result of OKT9 treatment. The transferrin receptor is also rapidly redistributed in response to OKT9 such that a lower percentage of the cellular receptors are displayed on the cell surface. OKT9 treatment also leads to a decrease in the total number of receptors participating in the transferrin cycle for cellular iron uptake. The reduction in iron uptake that results from the loss of receptors from the cycle leads to enhanced biosynthesis of the receptor. Receptors with bound OKT9 continue to participate in multiple cycles of iron uptake. However, OKT9 treatment appears to result in a relatively small increase per cycle in the departure of receptors from participation in iron uptake to a pathway leading to receptor degradation. Radiolabeled OKT9 is itself degraded by K562 cells and this degradation is inhibitable by leupeptin or chloroquine. In the presence of leupeptin, OKT9 treatment results in the enhanced intracellular accumulation of transferrin. Because the time involved in the transferrin cycle is shorter (12.5 min) than the normal half-life of the receptor (8 h), a small change in recycling efficiency caused by OKT9 treatment could account for the marked decrease in receptor half-life. In this paper the implications of these findings are discussed as they relate to systems in which receptor number is regulated by ligand.
mesh_terms: D000911:Antibodies, Monoclonal; D001666:Binding Sites, Antibody; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007501:Iron / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D011990:Receptors, Transferrin
chemical_list: D000911:Antibodies, Monoclonal; D007976:Leupeptins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D002738:Chloroquine; D007501:Iron; C032854:leupeptin