[Mechanisms of action of the EGF receptor system and control of cell growth]

The internalization process following cell surface receptor binding by epidermal growth factor (EGF) was studied. It was found that EGF is taken up into a dense, membranous organelle. This organelle is deficient in lysosomal enzyme activity and is biochemically dissimilar to the major lysosomal fraction. The uptake of EGF by this organelle was demonstrated in three different cell types representing three different species. Each of these cell types is highly responsive to the mitogenic action of EGF. These results indicate that EGF is endocytosed and delivered to a dense, nonlysosomal, organelle which is ubiquitous in fibroblasts. Furthermore, we demonstrate a close, positive correlation between EGF uptake into this fraction and the ability of cell to respond to the mitogen. A negative relationship between uptake into the subcellular fraction containing lysosomal enzymes and EGF-stimulated DNA synthesis was observed. Using numerous incubation conditions and inhibitors no exceptions to the correlation between EGF uptake into the lysosomal enzyme-deficient fraction and EGF-induced DNA synthesis were observed. These results suggest a role for this dense organelle in the production of a mitogenic signal.