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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Dec 15;90(24):11451–11455. doi: 10.1073/pnas.90.24.11451

Importance of receptor occupancy, concentration differences, and ligand exchange in the insulin-like growth factor I receptor system.

P Zhong 1, J F Cara 1, H S Tager 1
PMCID: PMC48001  PMID: 8265572

Abstract

We have investigated by use of placental membranes the mechanisms through which insulin-like growth factor I (IGF-I) comes to be associated with its alpha 2 beta 2 receptor heterotetramer. Our results suggest that (i) at low ligand concentrations, the formation and disruption of IGF-I--receptor complexes are consistent with ligand binding de novo to empty receptors but not with equilibria involving ligand dissociation; (ii) at higher ligand concentrations, rapid exchange arising from the formation and collapse of bis-liganded receptors leads to a transiently perturbed receptor state; (iii) these nonclassical IGF-I receptor interactions depend on close communication between the alpha beta halves of the alpha 2 beta 2 holo-IGF-I receptor; and (iv) related processes based on ligand exchange have the potential for serving as biological sensors of changes in ligand concentration, while ordinary binding processes serve as sensors of ligand concentrations themselves. A model is presented in which one or two molecules of ligand can be bound to an alpha 2 beta 2 IGF-I receptor heterotetramer, new ligand becomes associated with receptor by exchanging for a previously bound molecule of IGF-I, and fluctuating changes in free-ligand concentration might lead to enhanced IGF-I function.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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