Figure 1.

EGFR agonists differentially stimulate EGFR coupling in 32D/EGFR cells and MCF10A cells. Data in panels B, C, and D are compiled from at least three independent assays. Error bars indicate the standard error of the means. (A) The simulated agonist dose–response curves depicted here illustrate fundamental principals of pharmacology. Saturating concentrations of agonists X and Y yield the same degree of biological response (E_max). Thus, the concentration- and affinity-independent activities (efficacies or intrinsic activities) of these ligands are identical. Note that the efficacy/intrinsic activity of Z is lower than the efficacies/intrinsic activities of X and Y. The concentration of an agonist that is required to elicit a half-maximal biological response to that agonist (50% of E_max) is termed the EC₅₀. Therefore, the EC₅₀ of X is less than the EC₅₀ of Y and X is a more potent agonist than Y. If X and Y share the same receptor, in many cases X possesses higher affinity for the receptor than does Y. Despite the fact that X possesses greater efficacy/intrinsic activity than does Z, these two agonists possess identical potencies. (B and C) 32D/EGFR cells were treated with increasing concentrations of the indicated EGFR agonists. IL3 independence was evaluated; ligand potency (EC₅₀) and efficacy (E_max) are provided in Table I. (D) DNA synthesis in MCF10A cells was determined following treatment with increasing concentrations of the indicated EGFR agonists. DNA synthesis is expressed as a percentage of that stimulated by complete medium. Ligand potency (EC₅₀) and efficacy (E_max) are provided in Table I.