Persistence of Dimerization and Enzymatic Activity of Epidermal Growth Factor Receptor in the Absence of Epidermal Growth Factor

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Abstract
Dimerized and enzymatically active epidermal growth factor receptor, in the presence of saturating epidermal growth factor (EGF), was passed over a column containing an immunoadsorbent for EGF. The immunoadsorbent removed both EGF free in solution and EGF bound to EGF receptor, while EGF receptor passed through unimpeded. Both the dimerization of EGF receptor and the activation of its tyrosine kinase were arrested in samples containing EGF receptor that had been mixed with saturating EGF and then immediately passed over the immunoadsorbent for EGF. The EGF receptor in these samples, however, dimerized completely, and its tyrosine kinase became fully active upon readdition of EGF. Samples of EGF receptor that were fully dimerized and enzymatically active prior to being passed over the immunoadsorbent for EGF remained dimerized and enzymatically active even in the absence of bound EGF. The first-order rate constant for the inactivation of the tyrosine kinase of EGF receptor depleted of EGF was estimated by subtracting the rate constant of inactivation of the tyrosine kinase in samples replenished with EGF from the rate constant of inactivation of the tyrosine kinase in samples that had been depleted of EGF. The rate constant of inactivation was found to be 0.26 ± 0.06 h-1.