Annexin I as a potential inhibitor of insulin receptor protein tyrosine kinase

Biochem Biophys Res Commun. 1994 Sep 15;203(2):813-9. doi: 10.1006/bbrc.1994.2255.

Abstract

Insulin receptor (IR) purified from human placenta by wheat germ agglutinin affinity chromatography was incubated in the presence of insulin, [gamma-32P]ATP and annexin I. In parallel to its own tyrosine phosphorylation, annexin I promoted a dose-dependent inhibition of IR autophosphorylation (IC50 0.5 microM). This effect was specific for insulin-stimulated tyrosine kinase activity and required the N-terminal end of the protein containing the phosphorylatable Tyr21 residue. A pentadecapeptide encompassing residues 16-30 of human annexin I displayed a similar activity, but at higher concentrations. These data underscore a specific interaction of IR with annexin I, which should be considered as a potential physiological regulator of the effects of insulin on its target tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Amino Acid Sequence
  • Annexin A1 / chemistry
  • Annexin A1 / metabolism
  • Annexin A1 / pharmacology*
  • Female
  • Humans
  • Insulin / pharmacology
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Phosphorylation
  • Placenta / chemistry
  • Receptor, Insulin / antagonists & inhibitors*
  • Receptor, Insulin / metabolism

Substances

  • Annexin A1
  • Insulin
  • Peptide Fragments
  • Adenosine Triphosphate
  • Receptor, Insulin