[The dependence of the type of endocytosis of EGF receptor complexes on the basal level of tyrosine kinase activity in the epidermal growth factor receptor].

Two types of EGF-mediated endocytosis have been identified in A431 cells by the method of subcellular fractionation in Percoll density gradients. One ("slow") type of endocytosis is characterized by 125I-EGF retention in the fraction of light endosomes, while the other ("fast") type demonstrates efficient 125I-EGF transition into heavy endosomes and lysosomes. 32P-ATP phosphorylation assay of Percoll fractions, followed by alkaline treatment on the gels, has demonstrated that "slow" cells reveal an increased basal level of EGF-receptor tyrosine kinase (TK) activity compared to the "fast" cells. Pretreatment of "fast" cells with Mn2+, which was shown to induce TK stimulation without EGF (Mohammadi [correction of Muhammedi et al., 1993), caused a dramatic decrease in 125I-EGF transition to heavy endosomes and lysosomes. Analysis of tyrosine phosphorylation of the receptor, being performed in Mn(2+)-pretreated A431 cells, has confirmed the significant increase of 32P-incorporation into unoccupied EGFR. Taken together, our data suggest that sorting of internalized EGF-receptor complexes depends on the basal TK activity level of EGFR.