Long‐term epidermal growth factor–receptor internalization and processing in quiescent human fibroblasts

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Abstract
Epidermal growth factor is internalized into cells and concomitantly induces a massive clearance of up to 90% of its total surface receptors. The hormone‐receptor complex is delivered to lysosomes and degraded or inactivated. Lysosomotropic alkylamines block the degradation but not the binding‐or internalization of ligand‐receptor complexes and thus their presence results in a marked potentiation of intracellular accumulation of epidermal growth factor. We have used these alkylamines as pharmacological tools to trap internalized 125I‐labeled epidermal growth factor and now report that the residual population of epidermal growth factor receptors remaining on human fibroblasts after completion of the receptor clearance process is not only accessible for ligand binding but also directs the continued internalization and degradation of this growth factor over prolonged periods of time. We also show that down regulation of epidermal growth factor receptors does not result in desensitization of cells to the mitogenic response.