Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose

Cell. 1986 Jun 6;45(5):721-32. doi: 10.1016/0092-8674(86)90786-5.


Insulin stimulates the autophosphorylation of tyrosine residues of the beta subunit of the insulin receptor (IR); this modified insulin-independent kinase has increased activity toward exogenous substrates in vitro. We show here that replacement of one or both of the twin tyrosines (residues 1162 and 1163) with phenylalanine results in a dramatic reduction in or loss of insulin-activated autophosphorylation and kinase activity in vitro. In vivo, these mutations not only result in a substantial decrease in insulin-stimulated IR autophosphorylation but also in a parallel decrease in the insulin-activated uptake of 2-deoxyglucose. Furthermore, a truncated IR protein (lacking the last 112 amino acids) has an unstable beta subunit; this mutant has no kinase activity in vitro or in vivo and does not mediate insulin-stimulated uptake of 2-deoxyglucose. IR autophosphorylation is thus implicated in the regulation of IR activities, with tyrosines 1162 and 1163 as major sites of this regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cricetinae
  • Cricetulus
  • DNA / genetics
  • Deoxy Sugars / metabolism*
  • Deoxyglucose / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin / pharmacology*
  • Ovary
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor, Insulin / metabolism*
  • Transfection
  • Tyrosine / metabolism


  • Deoxy Sugars
  • Insulin
  • Tyrosine
  • DNA
  • Deoxyglucose
  • Protein-Tyrosine Kinases
  • Receptor, Insulin