Bovine fetuin is an inhibitor of insulin receptor tyrosine kinase.
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.
Mathews
S T
ST
Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA.
Srinivas
P R
PR
Leon
M A
MA
Grunberger
G
G
D000818:Animals; D002417:Cattle; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000302:isolation & purification / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007328:Insulin; D000509:alpha-Fetoproteins; D019000:Phosphotyrosine; D004247:DNA; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin