title: Basal autophosphorylation of insulin receptor occurs preferentially on the receptor conformation exhibiting high affinity for insulin and stabilizes this conformation.
abstract: Insulin signal transmission through the plasma membrane was studied in terms of relationship between basal autophosphorylation of the beta-subunit and the ability to bind insulin by the alpha-subunit of the insulin receptor. In a cell free system, receptors phosphorylated on tyrosine residues in the absence of insulin were separated from non-phosphorylated receptors using antiphosphotyrosine antibodies. Insulin binding assays were then performed on basally autophosphorylated and on non-phosphorylated receptors. We found that the tyrosine phosphorylated receptors, which corresponded to 25% of the total number of receptors, were accountable for 60-80% of insulin binding. Scatchard representation of binding data has shown that the plot corresponding to tyrosine phosphorylated receptors was localized above, and was steeper than the plot corresponding to non-phosphorylated receptors. These data make it likely that the conformation of alpha-subunit which favours ligand binding is connected to the conformation of beta-subunit which favours phosphate reception on tyrosine residues. Reciprocally, the high-affinity conformation of insulin receptor seems to become stabilized by basal autophosphorylation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale INSERM U145. Faculté de Médecine, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Kubar
authors.forename: N
authors.initials: N
authors.lastname: Rochet
mesh_terms: D000818:Animals; D002460:Cell Line; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D010766:Phosphorylation; D011487:Protein Conformation; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007328:Insulin; D014443:Tyrosine; D011972:Receptor, Insulin