The inhibition of the insulin receptor by the receptor protein PC-1 is not specific and results from the hydrolysis of ATP

Diabetes. 1996 Jul;45(7):980-3. doi: 10.2337/diab.45.7.980.

Abstract

The membrane protein plasma cell differentiation antigen 1 (PC-1) has been purified as an inhibitor of insulin receptor tyrosine kinase activity and has been implicated in the pathogenesis of NIDDM. However, we show here that PC-1 is a general protein kinase inhibitor in vitro and that this inhibition results from the hydrolysis of ATP by the intrinsic nucleotide pyrophosphatase activity of PC-1. Thus, the inhibition diminished with increasing ATP concentrations, and it was nullified when the ATP concentration was kept constant with a regenerating system or when ATP was added repetitively. When care was taken to avoid ATP depletion, PC-1 did not affect the insulin sensitivity of insulin receptor autophosphorylation. We conclude that the reported inhibition of insulin signaling by PC-1 does not result from a direct inhibition of the insulin receptor kinase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Casein Kinases
  • Cattle
  • Cell Membrane / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Insulin / pharmacology*
  • Kinetics
  • Liver / metabolism
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / pharmacology*
  • Muscle, Skeletal / enzymology
  • Myocardium / metabolism
  • Phosphoric Diester Hydrolases*
  • Phosphoric Monoester Hydrolases
  • Phosphorylase Kinase / isolation & purification
  • Phosphorylase Kinase / metabolism
  • Placenta / metabolism
  • Pregnancy
  • Protein Kinases / isolation & purification
  • Protein Kinases / metabolism
  • Pyrophosphatases*
  • Rabbits
  • Rats
  • Receptor, Insulin / antagonists & inhibitors*
  • Receptor, Insulin / metabolism*
  • Spleen / enzymology
  • Swine

Substances

  • Enzyme Inhibitors
  • Insulin
  • Membrane Glycoproteins
  • Adenosine Triphosphate
  • Protein Kinases
  • Phosphorylase Kinase
  • Receptor, Insulin
  • Casein Kinases
  • Phosphoric Monoester Hydrolases
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases