RT Journal Article SR Electronic T1 The Bivalent Ligand Hypothesis JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1 OP 14 VO 19 IS 1 A1 ALLEN P. MINTON YR 1981 UL http://molpharm.aspetjournals.org/content/19/1/1.abstract AB A model is presented wherein a single hormone molecule is treated as bearing two distinct regions capable of interaction with the cell surface: a specificity determinant which binds with high affinity and specificity to one class of cell surface sites called receptor, and a response determinant which binds with much lower affinity and specificity to a second class of cell surface sites called effector. It is postulated that the steady-state response elicited by the hormone is proportional to the amount of hormone bound to effector and that, under ordinary conditions, the ratio of effector sites to receptor sites is substantially less than unity, perhaps on the order of 0.1. In this model, the formation of a hormone-receptor complex does not serve to initiate directly the process by which the response is elicited, but rather to increase selectively the apparent affinity of effector for a specific hormone by several orders of magnitude. It is shown that this model is capable of qualitatively and semiquantitatively rationalizing, in a unified manner, a broad variety of experimental data on the relationship between hormone binding and steady-state response elicitation, in both the absence and presence of cross-linking agents such as lectins and anti-hormone and anti-receptor antibodies. ACKNOWLEDGMENTS I thank Dr. Y. Schechter for many stimulating discussions and Dr. D. Rodbard for critically reading and commenting upon the initial draft of this report. I also thank the Departments of Biophysics and Polymer Research, The Weizmann Institute of Science, for their hospitality.