Monensin, like methylamine, prevents degradation of 125I-epidermal growth factor, causes intracellular accumulation of receptors and blocks the mitogenic response.
Cultured fibroblasts were treated with the carboxylic ionophore monensin to study the effect on 125I-epidermal growth factor binding, internalization, and mitogenic response. Monensin enhanced the accumulation of the ligand by both preventing its degradation in lysosomes and causing a redistribution of receptors from the plasma membrane to an intracellular compartment. Monensin also prevented the mitogenic activity of EGF. This ionophore, like alkylamines, raises the pH of endosomes and lysosomes. These data are consistent with the hypothesis that exposure of EGF-receptor complexes to an acid environment is part of the pathway that leads to a mitogenic response.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008744:Methylamines / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology*; D008985:Monensin / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D005663:Furans; D007457:Iodine Radioisotopes; D008744:Methylamines; D008934:Mitogens; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D008985:Monensin; C027451:methylamine; D066246:ErbB Receptors