Bovine fetuin is an inhibitor of insulin receptor tyrosine kinase

Life Sci. 1997;61(16):1583-92. doi: 10.1016/s0024-3205(97)00737-6.


Fetuin has been identified earlier as the bovine homolog of the human plasma protein, alpha2-Heremans Schmid glycoprotein (alpha2-HSG). Although bovine fetuin shares over 70% amino acid sequence similarity with alpha2-HSG and rat fetuin, no common function(s) have been identified. We report that immunoaffinity purified bovine fetuin acts as an inhibitor of insulin receptor tyrosine kinase activity (IR-TKA) with half-maximal inhibition at 1.5 microM. In vitro, bovine fetuin (1.5 microM) blocked insulin-induced autophosphorylation of the human IR completely and the half-maximal inhibitory effect was observed at 0.5 microM. Incubation of HIRcB cells (rat1 fibroblasts transfected with wild-type human insulin receptor cDNA) with bovine fetuin (1.5 microM) inhibited insulin-induced tyrosine phosphorylation of the IR beta-subunit by 40%. In addition, bovine fetuin (2 microM) completely blocked insulin-stimulated DNA synthesis in H-35 rat hepatoma cells. Our results, together with earlier reports on rat fetuin and human alpha2-HSG, indicate a common IR-TK inhibitory function for fetuin homologs.

MeSH terms

  • Animals
  • Cattle
  • DNA / biosynthesis
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Insulin / pharmacology
  • Liver Neoplasms, Experimental / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rats
  • Receptor, Insulin / metabolism*
  • Tumor Cells, Cultured
  • alpha-Fetoproteins / isolation & purification
  • alpha-Fetoproteins / pharmacology*


  • Enzyme Inhibitors
  • Insulin
  • alpha-Fetoproteins
  • Phosphotyrosine
  • DNA
  • Protein-Tyrosine Kinases
  • Receptor, Insulin