Receptors for epidermal growth factor in the rat uterus.

Uterine membranes contain high affinity [dissociation constant (Kd) = 0.36 nM], saturable binding sites for [125I]iodo-epidermal growth factor (EGF). The binding of [125I] iodo-EGF is specific since it is abolished by excess unlabeled EGF but not by excess unlabeled insulin, fibroblast growth factor, or multiplication-stimulating activity. Incubation of [125I] iodo-EGF with uterine membranes, followed by chemical cross-linking with disuccinimidyl suberate and detergent extraction reveals a major species of specifically bound EGF (mol wt = 170,000) and a minor species (mol wt = 150,000) visualized by autoradiography of sodium dodecyl sulfate gels after electrophoresis of the extracts. In detergent-solubilized preparations EGF also stimulates the phosphorylation of major (mol wt = 170,000) and minor (mol wt = 150,000) species of identical molecular weight. The increased phosphorylation produced by incubation of membrane extracts with EGF occurs largely at tyrosine residues, as indicated by phosphoamino acid analysis. These results indicate that the rat uterus contains high affinity EGF binding sites with the properties expected of EGF receptors.