King A C, Cuatrecasas P
J Supramol Struct Cell Biochem. 1981;17(4):377-87. doi: 10.1002/jsscb.380170409.
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.
表皮生长因子被内化进入细胞，并同时诱导其总表面受体高达90%的大量清除。激素-受体复合物被转运至溶酶体并降解或失活。溶酶体亲和性烷基胺可阻断配体-受体复合物的降解，但不影响其结合或内化，因此它们的存在会导致表皮生长因子细胞内积累的显著增强。我们使用这些烷基胺作为药理学工具来捕获内化的125I标记的表皮生长因子，现在报告称，在受体清除过程完成后，人成纤维细胞上残留的表皮生长因子受体不仅可用于配体结合，而且在很长一段时间内还能指导这种生长因子的持续内化和降解。我们还表明，表皮生长因子受体的下调不会导致细胞对促有丝分裂反应脱敏。
