An evaluation of the cross-linking model for the interaction of insulin with its receptor.
The cross-linking model for insulin receptor interactions, in which a single insulin molecule may form a cross-link between an insulin receptor's alpha-subunits, has been expressed as a formal compartmental model and subjected to a systematic analysis, examining a number of predictions that have been made for this model. The kinetic parameters for the model were obtained by matching data from insulin receptor equilibrium binding studies and rates of formation of the insulin receptor complex. This analytical study has allowed a clear description of the kinetics of the ligand receptor complexes involved in such a mechanism. We conclude that the cross-linking model accounts for the anomaly of the 10-fold concentration difference in high- and low-affinity binding sites found when insulin binding is analyzed by conventional means. However, the phenomenon of acceleration of dissociation of labeled ligand by unlabeled ligand cannot be accounted for as an intrinsic part of the model. We suggest that this phenomenon arises from the destabilization of cross-link formation when a second insulin molecule binds.
Hammond
B J
BJ
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, United Kingdom.
Tikerpae
J
J
Smith
G D
GD
D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D046911:Macromolecular Substances; D008954:Models, Biological; D008956:Models, Chemical; D011972:Receptor, Insulin / Q000378:metabolism*
D003432:Cross-Linking Reagents; D007328:Insulin; D008024:Ligands; D046911:Macromolecular Substances; D011972:Receptor, Insulin