Detergent solubilization is a prerequisite for aggregation-induced stimulation of epidermal growth factor (EGF) receptor kinase.

Unlike EGF, concanavalin A and wheat germ agglutinin do not increase EGF receptor-kinase activity in intact A-431 membranes. However, they increase both autophosphorylation and phosphorylation of exogenous substrates about twice as much as EGF if the membranes are solubilized in detergent. Following solubilization, autophosphorylation due to the combined presence of a lectin and EGF is additive suggesting that each increases kinase activity by a different mechanism. These different mechanisms were studied by autophosphorylating membranes at increasing detergent concentrations after they had been permeabilized to [gamma-32P]ATP with alamethicin. As the detergent concentration increased, EGF stimulated autophosphorylation decreased 3-fold and 6-fold for the native 170 kDa receptor and for a protease-generated 150 kDa receptor form, respectively. However, in the presence of either lectin the same increase in detergent concentration only slightly altered the autophosphorylation rates which never exceeded the rate measured in the absence of EGF and detergent. Hence, the lectins increase kinase activity in solubilized membranes by preventing the adverse effects of detergent on the receptor-kinase and may not be useful models for how EGF activates its receptor.