Basal autophosphorylation of insulin receptor occurs preferentially on the receptor conformation exhibiting high affinity for insulin and stabilizes this conformation

Cell Signal. 1990;2(6):587-94. doi: 10.1016/0898-6568(90)90081-k.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Insulin / metabolism*
  • Kinetics
  • Phosphorylation
  • Protein Conformation
  • Receptor, Insulin / metabolism*
  • Signal Transduction / physiology
  • Tyrosine / metabolism

Substances

  • Insulin
  • Tyrosine
  • Receptor, Insulin