When [125I]iodoepidermal growth factor is incubated with freshly isolated rat hepatocytes, cell-associated radioactivity reaches apparent steady state by 60 min at 20 C and by 30 min of incubation at 37 C. When the distribution of cell-associated radioactivity is studied at different times of incubation by quantitative electron microscopic autoradiography, the ligand initially associates with the plasma membrane and is progressively internalized as a function of time. The internalized ligand preferentially associates with lysosome-like structures. Qualitatively, these events are similar to those previously obtained with labeled insulin and glucagon in this cell, but quantitatively, the internalization of epidermal growth factor is much greater. The data suggest that the ligand or its specific receptor rather than the cell type is the major determinant of the rate of internalization.
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