PubMed:3262110 JSONTXT

{"project":"NEUROSES","denotations":[{"id":"T1","span":{"begin":83,"end":87},"obj":"PATO_0000469"},{"id":"T2","span":{"begin":199,"end":203},"obj":"PATO_0000469"},{"id":"T3","span":{"begin":1119,"end":1123},"obj":"PATO_0000469"},{"id":"T4","span":{"begin":356,"end":359},"obj":"PATO_0000471"},{"id":"T5","span":{"begin":1896,"end":1899},"obj":"PATO_0000471"},{"id":"T6","span":{"begin":443,"end":450},"obj":"PATO_0000006"},{"id":"T7","span":{"begin":474,"end":482},"obj":"PATO_0002118"},{"id":"T8","span":{"begin":1967,"end":1975},"obj":"PATO_0002118"},{"id":"T9","span":{"begin":483,"end":491},"obj":"PATO_0002070"},{"id":"T10","span":{"begin":1976,"end":1984},"obj":"PATO_0002070"},{"id":"T11","span":{"begin":720,"end":727},"obj":"PATO_0000392"},{"id":"T12","span":{"begin":1877,"end":1884},"obj":"PATO_0000392"},{"id":"T16","span":{"begin":934,"end":938},"obj":"PATO_0001470"},{"id":"T17","span":{"begin":934,"end":938},"obj":"PATO_0000161"},{"id":"T18","span":{"begin":982,"end":987},"obj":"PATO_0000002"},{"id":"T19","span":{"begin":995,"end":1001},"obj":"PATO_0000461"},{"id":"T20","span":{"begin":1277,"end":1282},"obj":"PATO_0000083"},{"id":"T21","span":{"begin":1295,"end":1304},"obj":"PATO_0000470"},{"id":"T22","span":{"begin":1525,"end":1532},"obj":"CHEBI_24621"},{"id":"T23","span":{"begin":1855,"end":1863},"obj":"PATO_0000070"}],"text":"Anomalous binding of epidermal growth factor to A431 cells is due to the effect of high receptor densities and a saturable endocytic system.\nThis study was conducted to determine how extraordinarily high numbers of epidermal growth factor receptors (EGF-R) affected the binding and internalization of EGF in the transformed cell line A431. I found that at low EGF concentrations, the kinetics of binding behaved as a nonsaturable, first-order process showing no evidence of multiple-affinity classes of receptors. However, EGF dissociation rates were strongly dependent on the degree of receptor occupancy in both intact cells and isolated membranes. This occupancy-dependent dissociation appears to be due to diffusion-limited binding. EGF-induced receptor internalization was rapid and first order when the absolute number of occupied receptors was below 4 x 10(3) min-1. However, at higher occupancies the specific internalization rate progressively declined to a final limiting value of 20% normal. The saturation of EGF-R endocytosis was specific since internalization of transferrin receptors was not affected by high concentrations of either transferrin or EGF. Saturation of EGF-R endocytosis probably involves a specific component of the endocytic pathway since fluid phase endocytosis increased coordinately with EGF-R occupancy. I conclude that there are several aspects of EGF-R dynamics on A431 cells are neither similar to the behavior of EGF-R in other cell types nor similar to the reported behavior of other hormone receptors. Although A431 cells have an extraordinary number of EGF-R, they do not seem to have corresponding levels of at least two other crucial cell surface components: one that mediates EGF-induced rapid receptor internalization and one that attenuates EGF-induced membrane responses. These factors, in addition to the presence of diffusion-limited binding at low EGF concentrations, are probably responsible for the appearance of multiple-affinity classes of receptors in this cell type."}